Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S2053229615022305/fn3209sup1.cif | |
Portable Document Format (PDF) file https://doi.org/10.1107/S2053229615022305/fn3209sup4.pdf | |
Structure factor file (CIF format) https://doi.org/10.1107/S2053229615022305/fn3209Comp_XIIsup5.hkl | |
Structure factor file (CIF format) https://doi.org/10.1107/S2053229615022305/fn3209Comp_XVsup6.hkl |
CCDC references: 1438133; 1438132
Eribulin mesylate is a structurally truncated synthetic analogue of Halichondrin B (Hirata & Uemura, 1986; Kishi et al., 1994), the most bioactive natural product isolated from the marine sponge Halichondria okadai commonly found off the coasts of Japan and New Zealand. Eribulin mesylate (Halaven Reg) interferes with microtubule dynamics (Smith et al., 2010) and was approved in November 2010 by the United States Food and Drug Administration (USFDA) for the treatment of metastatic breast cancer (Towle et al., 2001). The structure of eribulin resembles a macrocyclic ketone showcasing a fully synthetic drug available on the market today. 19 of the 36 C atoms that constitute the skeleton of the molecule are stereogenic in nature.
The structural framework of eribulin is built up by assembling three key fragments: (i) the C1–C13 aldehyde fragment I, denoted (III), (ii) the C14–C26 vinyl triflate fragment II, denoted (IV), and (iii) the C27–C35 phenyl sulfone fragment III, denoted (V) (Fig. 1).
Several synthetic routes have been used for the preparation of eribulin, (I), each of which utilize the same strategy described by Kishi and co-workers known for their pioneering work on the total synthesis of Halichondrins, and Halichondrin B in particular (Aicher et al., 1992). Over the years, synthetic routes have evolved continuously, with scale-up and route refinement as the key areas of improvement (Yu et al., 2013; Austad et al., 2013).
The three key fragments (III)–(V) (Fig. 1) are synthesized in 15–20 stages each and have been reported in detail. In the later stages, (IV) and (V) are subjected to Nozaki–Hiyama–Kishi (NHK) coupling (Hiyama et al., 1981; Jin et al., 1986) (Fig. 1) to yield fragment IV [denoted (II), the C14–C35 fragment], which is then coupled with (III) under basic conditions. The final stages (Fig. 2) involve a macrocyclization achieved again through NHK coupling of (VIII), the formation of cyclic ketal (IX) and the conversion of terminal diol (X) to an in situ epoxide on which the primary amine is added to finally realize eribulin mesylate, (I).
The goal of our synthesis was to conduct feasibility studies and develop an optimized and scalable process for the preparation of (I). Owing to the presence of 19 stereocentres in this molecule, it was required to continuously ensure the correct stereoisomer at every stage of this extensive synthesis. The important check-point was to characterize newly formed stereocentres in selected molecules through two-dimensional NMR (2D-NMR) data. There were, however, instances where 2D-NMR data were not conclusive enough to prove the absolute stereochemistry or there was a need to prove the molecular geometry for subsequent reactions. Hence, single-crystal X-ray diffraction analysis was employed to identified intermediates of compounds (III)–(V) in order to conclusively establish the structures (Fig. 1).
The single-crystal X-ray structure of (II) has been reported previously (Austad et al., 2013). Also a 3,5-dinitrophenyl ester derivative of the alcohol variant of (V) (Fig. 1) has been reported, denoted (Va) (Yang et al., 2009) (Scheme 1).
We report here the single-crystal X-ray data for two relatively important intermediates of (III) and (V) which have an important bearing on the structural orchestration of the eribulin molecule.
The selected intermediate of (III) is 3,4:6,7-di-O-cyclohexylidene-D-glycero-α-L-talo-heptopyranose, (XII), whose stereochemistry has important implications for the C-allylation product (XIV) two stages later (Fig. 3). The synthesis of (III) starts with D-gulono-γ-lactone (Fig. 3) having two sets of vicinal diol groups, the stereochemistries of which are fixed. The gulono lactone is converted into its lactol which reacts with MeOCH2PPh3Cl under Wittig conditions to produce hydroxyalkene (XI). The Sharpless dihydroxylation protocol through which (XII) is finally obtained involves a catalytic osmylation (Kolb et al., 1994) of (XI) using the double stereo-differentiation strategy (Masamme et al., 1985). It provides a 4:1 mixture of diastereoisomers, which after purification delivers (XII) as a single diastereoisomer in the form of a white crystalline solid. This mechanism should force the H atom on C1 (i.e. H1) to assume a different orientation on the desired diastereoisomer, as compared to the other H atoms on atoms C2–C5 (Fig. 4). However, the nuclear Overhauser effect spectroscopy (NOESY) of this molecule unusually showed that atom H1 has an interaction with H2, which means that they are in the same plane (Fig. 5). Further insight into this molecule could be provided by single-crystal X-ray diffraction to align the mechanistic rationale and determine the absolute configuration. Compound (XII) is then subjected to acetylation yielding tetraacetate (XIII). C-Allylation of (XIII) using methyl 3-trimethylsilylpent-4-enoate (also known as the Kishi alkene) retains the configuration on C1 after displacement of the O-acetyl group to yield allylic ester (XIV) which exists as 1:1 conformers (Stamos & Kishi, 1996).
The second intermediate, (2R,3R,4R,5S)-5-allyltetrahydro-2-[(S)-2,3-dihydroxypropyl]-4-[(phenylsulfonyl)methyl]furan-3-ol, (XV), from the synthesis of (V) is obtained through a sequence of 15 chemical transformations (Fig. 6) starting from D-glucorono-6,3-lactone (Yang et al., 2009) [see (Va) in Scheme 1]. The correlation NMR spectra (COSY) of the tetrahydrofuran framework present in (V) and its intermediates show that the vicinal H atoms on C2 and C3 do not correlate. It became vital to understand the spatial orientation of these two H atoms along with the structural framework so as to deduce the relative configuration of this molecule. Further, the C6—C7 diol functionality is introduced through asymmetric dihydroxylation in a 3:1 diastereoisomeric ratio in (XX). The undesired isomer after two stages at (XXI) is removed through recrystallization. Our attempts to prepare single crystal of (XXI) were unsuccessful. We then went five stages further to triol (XV) (Fig. 4) which exists as a white crystalline solid and was successful crystallized.
Compounds (XII) and (XV) were prepared according to existing synthesis routes. NMR spectra were recorded at room temperature using an Agilent 500 MHz spectrometer. 1H chemical shifts are reported in p.p.m. values referenced to tetramethylsilane (TMS, 0.0 p.p.m.). 13C chemical shifts are reported in p.p.m. referenced to the solvent resonance of 39.5 p.p.m. for DMSO-d6.
1H NMR (500 MHz, DMSO-d6): δ 1.30–1.35 (m, 4H), 1.42–1.60 (m, 16H), 3.43–3.44 (dd, J = 3 Hz, 1.5 Hz, 1H), 3.56–3.58 (dd, J = 2, 1.5 Hz, 1H), 3.66–3.69 (t, 1H), 3.94–3.97 (q, 1H), 4.00–4.05 (q, 1H), 4.14–4.16 (dd, J = 2.5, 1.5 Hz, 1H), 4.29–4.32 (dd, J = 2.5, 3 Hz, 1H), 4.79–4.80 (d, J = 6 Hz, 1H), 5.23–5.24 (d, 1 H), 6.34–6.35 (d, 1H).
13C NMR (125 MHz, DMSO-d6): δ 23.38 (–CH2), 23.44 (–CH2), 23.50 (–CH2), 23.62 (–CH2), 24.63 (–CH2), 24.66 (–CH2), 34.60 (–CH2), 34.98 (–CH2), 35.47 (–CH2), 35.86 (–CH2), 64.78 (–CH2), 68.87 (–CH), 70.93 (–CH), 74.20 (–CH), 74.85 (–CH), 75.65 (–CH), 93.59 (–CH), 108.84 (quaternary C), 109.48 (quaternary C).
1H NMR (500 MHz, DMSO-d6): δ 1.51–1.53 (m, 1H), 1.69–1.71 (m, 1H), 2.00–2.01 (t, 1H), 2.22–2.54 (m, 2H), 3.25–3.28 (m, 2H), 3.31–3.32 (d, 1H), 3.43–3.47 (m, 2H), 3.53–3.54 (q, 1H), 3.72–3.73 (q, 1H), 3.95–3.97 (t, 1H), 4.39–4.42 (m, 2H), 4.80–4.81 (d, J = 5 Hz, 1H), 4.87–4.90 (t, 2H), 5.61–5.69 (m, 1H), 7.64–7.67 (t, 2H), 7.73–7.76 (t, 1H), 7.92-7.93 (d, J = 8 Hz, 2H).
13C NMR (125 MHz, DMSO-d6): δ 32.53 (–CH2), 38.75 (–CH2), 47.49 (–CH), 56.52 (–CH2), 65.80 (–CH2), 68.89 (–CH), 75.75 (–CH), 78.64 (–CH), 81.20 (–CH), 116.67 (–CH2), 127.78 (2-aryl-CH), 129.38 (2-aryl-CH), 133.83 (–CH), 135.06 (–CH), 139.31 (quaternary C).
Compound (XII) was crystallized by slow evaporation from a solution in methanol, yielding crystals suitable for single-crystal X-ray diffraction analysis. Compound (XV) is recrystallized by slow evaporation from a solution in a mixture of toluene and n-butanol (7:1 v/v), yielding crystals in the form of colourless prisms ideal for single-crystal X-ray diffraction analysis.
Crystal data, data collection and structure refinement details for (XII) and (XV) are summarized in Table 1. H atoms were placed in geometrically optimized positions and constrained to ride on their parent atoms with C—H = 0.96 (methyl), 0.97 (methylene) and 0.98 Å (methine), and O—H = 0.82 Å for (XII) and C—H = 0.95 (aryl), 0.99 (methylene) and 1.00 Å (methine), and O—H = 0.84 Å for (XV). Displacement parameters for all H atoms were assigned as Uiso(H) = 1.2Ueq(C,O). The orientation of the solvent methyl group in (XII) was allowed to rotate about the C—O bond to find the best fit to the observed electron density peaks and the hydroxy groups in (XV) were similarly allowed to rotate. For (XII), the hydroxy groups at O3 and O9 were also treated this way, but the hydroxy group at O2 was oriented such that the H atom was in a staggered position with respect to the substituents on the parent C atom.
For compound (XII), the relative structure was deduced based on known stereochemistry discussed below, whereas for (XV), the structure was deduced based on the Flack parameter [0.00 (3); Parsons et al., 2013].
The single-crystal X-ray structure of (XII) (Fig. 4) shows that the compound crystallizes with a methanol solvent molecule. The cyclohexylidene rings assume chair conformations, whereas the five-membered rings have envelope conformations. The molecules pack together in the solid state with a few intermolecular hydrogen bonds. The O2 and O3 hydroxy groups form hydrogen-bonding interactions with the methanol atom O9 and with the O6 atom of another molecule, respectively (Table 2).
The NOESY spectrum of (XII) (Fig. 5) shows that the H atom at C1 (H1A, 4.8 p.p.m.) shows an interaction with H2B, which was unusual as per mechanistic understanding (Table 3). The single-crystal X-ray diffraction data, however, confirm the mechanistic rationale wherein atom H1A is in a different plane from the other H atoms (those on on C2, C3, C4 and C5) of the tetrahydropyran ring. Furthermore, the H1A···H2B distance of 2.83 Å supports a NOESY interaction between these atoms. The interatomic distance between atoms C1 and C2 is 1.523 (3) Å. Also, atoms H1A and H5A are on opposite sides of the C1—O1—C5 unit, with an H1A···H5A interatomic distance of 3.55 Å. The interatomic distance between atoms C1 and H5A is 2.68 Å, and that between atoms C5 and H1A is 3.12 Å.
We further focused our attention on the starting material, i.e. D-gulono-lactone, which has a specific optical rotation (SOR) of -55°. The stereochemistry at atoms C3 and C4 in this molecule are fixed and this is carried through onto atoms C3 and C4 in (XII). The NOESY spectrum of (XII) showed strong contours for the interaction of atoms H2B and H3B, suggesting them to be in the same spatial orientation. Furthermore, though atom H1A showed a weak interaction with H2B, as suggested by NOESY, this was ruled out as the X-ray structure suggested that H1A is in an opposite plane to H2B. The NOESY interaction for H1A and H2B must stem from the atoms coming into close proximity with each other (2.8 Å) as discussed previously. We were thus able to establish the absolute configuration of (XII) in this manner with the aid of both the NOESY and the single-crystal X-ray data.
The single-crystal X-ray analysis of (XV) shows that the tetrahydrofuran ring has an envelope conformation (Fig. 7). Again the molecules pack together in the solid state with few inter- or intramolecular hydrogen bonds. The O2 and O3 hydroxy groups form an intramolecular hydrogen-bonding interaction and also an intermolecular hydrogen-bonding interaction with atoms O1 and O4 of another molecule (Table 4). Also, atom O4 forms an intermolecular hydrogen-bonding interaction with atom O2 of another molecule, and atom O3 forms an intermolecular hydrogen-bonding interaction with atom O4 of another molecule.
We were particularly interested to see the orientation of the vicinal H atoms on atoms C2 and C3 of the tetrahydrofuran ring, as these two H atoms show an unusually weak interaction in the COSY spectrum (Fig. 8; H2A at 4 p.p.m. and H3A at 2 p.p.m.). This can happen when the H atoms form a 90° dihedral angle. The Karplus relationship is based on this observation that vicinal H–H couplings will be at a maximum for H atoms with dihedral angles of 180 and 0° (an anti or eclipsed relationship results in optimal orbital overlap) and that coupling (3JHH) will be minimal (near 0°) for H atoms that are 90° from each other. Atoms H2A and H3A, being in near perpendicular positions with respect to each other, possess minimal J coupling. To add to this, the tetrahydrofuran ring assumes an envelope confirmation giving rise to the feature observed for the vicinal H atoms. This observation was further substantiated with the aid of the single-crystal X-ray diffraction data. The bond angles C2—C3—H3A of 110° and C3—C2—H2A of 111° support the COSY spectrum. The H2A···H3A interatomic distance is 2.71 Å (Table 5).
In conclusion, we have synthesized and generated single-crystal X-ray diffraction data for two compounds, (XII) and (XV), having important structural implications for the Eribulin framework. Compound (XII) is the starting point of structural integrity for fragment I, (III) (Fig. 1), and thus needed to be thoroughly characterized before proceeding forward with the synthesis. The 2D-NOESY spectrum deduced that atom H1A interacted with atom H2B, which was contrary to the mechanistic observations. The single-crystal X-ray analysis, however, confirmed that this was the case and atom H1A in a different plane to the other H atoms on the tetrahydropyran ring. This strategy delivers the correct framework for onward C-allylation and subsequent cyclization.
Compound (XV) gave a typical observation wherein the vicinal H atoms at C2 and C3 on the tetrahydrofuran ring showed a weak interaction in the 2D-COSY spectrum. This observation can result from H atoms exhibiting a near perpendicular dihedral angle with respect to each other. Although 2D-NMR techniques helped in deciphering the relative stereochemistry, there remained ambiguity with respect to atoms H2A and H3A since there was no correlation found among them in the COSY analysis. A single crystal of this compound was thus prepared and its X-ray diffraction data showed that the H atoms at C2 and C3 were in a perpendicular orientation with respect to each other. The absolute configuration of the molecule was also determined. The present study thus proves unambiguously that the two H atoms are positioned on the tetrahydrofuran ring as depicted in Fig. 7. This observation was helpful in deducing the structural framework of fragment III [see (V) in Fig. 1].
Eribulin mesylate is a structurally truncated synthetic analogue of Halichondrin B (Hirata & Uemura, 1986; Kishi et al., 1994), the most bioactive natural product isolated from the marine sponge Halichondria okadai commonly found off the coasts of Japan and New Zealand. Eribulin mesylate (Halaven Reg) interferes with microtubule dynamics (Smith et al., 2010) and was approved in November 2010 by the United States Food and Drug Administration (USFDA) for the treatment of metastatic breast cancer (Towle et al., 2001). The structure of eribulin resembles a macrocyclic ketone showcasing a fully synthetic drug available on the market today. 19 of the 36 C atoms that constitute the skeleton of the molecule are stereogenic in nature.
The structural framework of eribulin is built up by assembling three key fragments: (i) the C1–C13 aldehyde fragment I, denoted (III), (ii) the C14–C26 vinyl triflate fragment II, denoted (IV), and (iii) the C27–C35 phenyl sulfone fragment III, denoted (V) (Fig. 1).
Several synthetic routes have been used for the preparation of eribulin, (I), each of which utilize the same strategy described by Kishi and co-workers known for their pioneering work on the total synthesis of Halichondrins, and Halichondrin B in particular (Aicher et al., 1992). Over the years, synthetic routes have evolved continuously, with scale-up and route refinement as the key areas of improvement (Yu et al., 2013; Austad et al., 2013).
The three key fragments (III)–(V) (Fig. 1) are synthesized in 15–20 stages each and have been reported in detail. In the later stages, (IV) and (V) are subjected to Nozaki–Hiyama–Kishi (NHK) coupling (Hiyama et al., 1981; Jin et al., 1986) (Fig. 1) to yield fragment IV [denoted (II), the C14–C35 fragment], which is then coupled with (III) under basic conditions. The final stages (Fig. 2) involve a macrocyclization achieved again through NHK coupling of (VIII), the formation of cyclic ketal (IX) and the conversion of terminal diol (X) to an in situ epoxide on which the primary amine is added to finally realize eribulin mesylate, (I).
The goal of our synthesis was to conduct feasibility studies and develop an optimized and scalable process for the preparation of (I). Owing to the presence of 19 stereocentres in this molecule, it was required to continuously ensure the correct stereoisomer at every stage of this extensive synthesis. The important check-point was to characterize newly formed stereocentres in selected molecules through two-dimensional NMR (2D-NMR) data. There were, however, instances where 2D-NMR data were not conclusive enough to prove the absolute stereochemistry or there was a need to prove the molecular geometry for subsequent reactions. Hence, single-crystal X-ray diffraction analysis was employed to identified intermediates of compounds (III)–(V) in order to conclusively establish the structures (Fig. 1).
The single-crystal X-ray structure of (II) has been reported previously (Austad et al., 2013). Also a 3,5-dinitrophenyl ester derivative of the alcohol variant of (V) (Fig. 1) has been reported, denoted (Va) (Yang et al., 2009) (Scheme 1).
We report here the single-crystal X-ray data for two relatively important intermediates of (III) and (V) which have an important bearing on the structural orchestration of the eribulin molecule.
The selected intermediate of (III) is 3,4:6,7-di-O-cyclohexylidene-D-glycero-α-L-talo-heptopyranose, (XII), whose stereochemistry has important implications for the C-allylation product (XIV) two stages later (Fig. 3). The synthesis of (III) starts with D-gulono-γ-lactone (Fig. 3) having two sets of vicinal diol groups, the stereochemistries of which are fixed. The gulono lactone is converted into its lactol which reacts with MeOCH2PPh3Cl under Wittig conditions to produce hydroxyalkene (XI). The Sharpless dihydroxylation protocol through which (XII) is finally obtained involves a catalytic osmylation (Kolb et al., 1994) of (XI) using the double stereo-differentiation strategy (Masamme et al., 1985). It provides a 4:1 mixture of diastereoisomers, which after purification delivers (XII) as a single diastereoisomer in the form of a white crystalline solid. This mechanism should force the H atom on C1 (i.e. H1) to assume a different orientation on the desired diastereoisomer, as compared to the other H atoms on atoms C2–C5 (Fig. 4). However, the nuclear Overhauser effect spectroscopy (NOESY) of this molecule unusually showed that atom H1 has an interaction with H2, which means that they are in the same plane (Fig. 5). Further insight into this molecule could be provided by single-crystal X-ray diffraction to align the mechanistic rationale and determine the absolute configuration. Compound (XII) is then subjected to acetylation yielding tetraacetate (XIII). C-Allylation of (XIII) using methyl 3-trimethylsilylpent-4-enoate (also known as the Kishi alkene) retains the configuration on C1 after displacement of the O-acetyl group to yield allylic ester (XIV) which exists as 1:1 conformers (Stamos & Kishi, 1996).
The second intermediate, (2R,3R,4R,5S)-5-allyltetrahydro-2-[(S)-2,3-dihydroxypropyl]-4-[(phenylsulfonyl)methyl]furan-3-ol, (XV), from the synthesis of (V) is obtained through a sequence of 15 chemical transformations (Fig. 6) starting from D-glucorono-6,3-lactone (Yang et al., 2009) [see (Va) in Scheme 1]. The correlation NMR spectra (COSY) of the tetrahydrofuran framework present in (V) and its intermediates show that the vicinal H atoms on C2 and C3 do not correlate. It became vital to understand the spatial orientation of these two H atoms along with the structural framework so as to deduce the relative configuration of this molecule. Further, the C6—C7 diol functionality is introduced through asymmetric dihydroxylation in a 3:1 diastereoisomeric ratio in (XX). The undesired isomer after two stages at (XXI) is removed through recrystallization. Our attempts to prepare single crystal of (XXI) were unsuccessful. We then went five stages further to triol (XV) (Fig. 4) which exists as a white crystalline solid and was successful crystallized.
Compounds (XII) and (XV) were prepared according to existing synthesis routes. NMR spectra were recorded at room temperature using an Agilent 500 MHz spectrometer. 1H chemical shifts are reported in p.p.m. values referenced to tetramethylsilane (TMS, 0.0 p.p.m.). 13C chemical shifts are reported in p.p.m. referenced to the solvent resonance of 39.5 p.p.m. for DMSO-d6.
1H NMR (500 MHz, DMSO-d6): δ 1.30–1.35 (m, 4H), 1.42–1.60 (m, 16H), 3.43–3.44 (dd, J = 3 Hz, 1.5 Hz, 1H), 3.56–3.58 (dd, J = 2, 1.5 Hz, 1H), 3.66–3.69 (t, 1H), 3.94–3.97 (q, 1H), 4.00–4.05 (q, 1H), 4.14–4.16 (dd, J = 2.5, 1.5 Hz, 1H), 4.29–4.32 (dd, J = 2.5, 3 Hz, 1H), 4.79–4.80 (d, J = 6 Hz, 1H), 5.23–5.24 (d, 1 H), 6.34–6.35 (d, 1H).
13C NMR (125 MHz, DMSO-d6): δ 23.38 (–CH2), 23.44 (–CH2), 23.50 (–CH2), 23.62 (–CH2), 24.63 (–CH2), 24.66 (–CH2), 34.60 (–CH2), 34.98 (–CH2), 35.47 (–CH2), 35.86 (–CH2), 64.78 (–CH2), 68.87 (–CH), 70.93 (–CH), 74.20 (–CH), 74.85 (–CH), 75.65 (–CH), 93.59 (–CH), 108.84 (quaternary C), 109.48 (quaternary C).
1H NMR (500 MHz, DMSO-d6): δ 1.51–1.53 (m, 1H), 1.69–1.71 (m, 1H), 2.00–2.01 (t, 1H), 2.22–2.54 (m, 2H), 3.25–3.28 (m, 2H), 3.31–3.32 (d, 1H), 3.43–3.47 (m, 2H), 3.53–3.54 (q, 1H), 3.72–3.73 (q, 1H), 3.95–3.97 (t, 1H), 4.39–4.42 (m, 2H), 4.80–4.81 (d, J = 5 Hz, 1H), 4.87–4.90 (t, 2H), 5.61–5.69 (m, 1H), 7.64–7.67 (t, 2H), 7.73–7.76 (t, 1H), 7.92-7.93 (d, J = 8 Hz, 2H).
13C NMR (125 MHz, DMSO-d6): δ 32.53 (–CH2), 38.75 (–CH2), 47.49 (–CH), 56.52 (–CH2), 65.80 (–CH2), 68.89 (–CH), 75.75 (–CH), 78.64 (–CH), 81.20 (–CH), 116.67 (–CH2), 127.78 (2-aryl-CH), 129.38 (2-aryl-CH), 133.83 (–CH), 135.06 (–CH), 139.31 (quaternary C).
The single-crystal X-ray structure of (XII) (Fig. 4) shows that the compound crystallizes with a methanol solvent molecule. The cyclohexylidene rings assume chair conformations, whereas the five-membered rings have envelope conformations. The molecules pack together in the solid state with a few intermolecular hydrogen bonds. The O2 and O3 hydroxy groups form hydrogen-bonding interactions with the methanol atom O9 and with the O6 atom of another molecule, respectively (Table 2).
The NOESY spectrum of (XII) (Fig. 5) shows that the H atom at C1 (H1A, 4.8 p.p.m.) shows an interaction with H2B, which was unusual as per mechanistic understanding (Table 3). The single-crystal X-ray diffraction data, however, confirm the mechanistic rationale wherein atom H1A is in a different plane from the other H atoms (those on on C2, C3, C4 and C5) of the tetrahydropyran ring. Furthermore, the H1A···H2B distance of 2.83 Å supports a NOESY interaction between these atoms. The interatomic distance between atoms C1 and C2 is 1.523 (3) Å. Also, atoms H1A and H5A are on opposite sides of the C1—O1—C5 unit, with an H1A···H5A interatomic distance of 3.55 Å. The interatomic distance between atoms C1 and H5A is 2.68 Å, and that between atoms C5 and H1A is 3.12 Å.
We further focused our attention on the starting material, i.e. D-gulono-lactone, which has a specific optical rotation (SOR) of -55°. The stereochemistry at atoms C3 and C4 in this molecule are fixed and this is carried through onto atoms C3 and C4 in (XII). The NOESY spectrum of (XII) showed strong contours for the interaction of atoms H2B and H3B, suggesting them to be in the same spatial orientation. Furthermore, though atom H1A showed a weak interaction with H2B, as suggested by NOESY, this was ruled out as the X-ray structure suggested that H1A is in an opposite plane to H2B. The NOESY interaction for H1A and H2B must stem from the atoms coming into close proximity with each other (2.8 Å) as discussed previously. We were thus able to establish the absolute configuration of (XII) in this manner with the aid of both the NOESY and the single-crystal X-ray data.
The single-crystal X-ray analysis of (XV) shows that the tetrahydrofuran ring has an envelope conformation (Fig. 7). Again the molecules pack together in the solid state with few inter- or intramolecular hydrogen bonds. The O2 and O3 hydroxy groups form an intramolecular hydrogen-bonding interaction and also an intermolecular hydrogen-bonding interaction with atoms O1 and O4 of another molecule (Table 4). Also, atom O4 forms an intermolecular hydrogen-bonding interaction with atom O2 of another molecule, and atom O3 forms an intermolecular hydrogen-bonding interaction with atom O4 of another molecule.
We were particularly interested to see the orientation of the vicinal H atoms on atoms C2 and C3 of the tetrahydrofuran ring, as these two H atoms show an unusually weak interaction in the COSY spectrum (Fig. 8; H2A at 4 p.p.m. and H3A at 2 p.p.m.). This can happen when the H atoms form a 90° dihedral angle. The Karplus relationship is based on this observation that vicinal H–H couplings will be at a maximum for H atoms with dihedral angles of 180 and 0° (an anti or eclipsed relationship results in optimal orbital overlap) and that coupling (3JHH) will be minimal (near 0°) for H atoms that are 90° from each other. Atoms H2A and H3A, being in near perpendicular positions with respect to each other, possess minimal J coupling. To add to this, the tetrahydrofuran ring assumes an envelope confirmation giving rise to the feature observed for the vicinal H atoms. This observation was further substantiated with the aid of the single-crystal X-ray diffraction data. The bond angles C2—C3—H3A of 110° and C3—C2—H2A of 111° support the COSY spectrum. The H2A···H3A interatomic distance is 2.71 Å (Table 5).
In conclusion, we have synthesized and generated single-crystal X-ray diffraction data for two compounds, (XII) and (XV), having important structural implications for the Eribulin framework. Compound (XII) is the starting point of structural integrity for fragment I, (III) (Fig. 1), and thus needed to be thoroughly characterized before proceeding forward with the synthesis. The 2D-NOESY spectrum deduced that atom H1A interacted with atom H2B, which was contrary to the mechanistic observations. The single-crystal X-ray analysis, however, confirmed that this was the case and atom H1A in a different plane to the other H atoms on the tetrahydropyran ring. This strategy delivers the correct framework for onward C-allylation and subsequent cyclization.
Compound (XV) gave a typical observation wherein the vicinal H atoms at C2 and C3 on the tetrahydrofuran ring showed a weak interaction in the 2D-COSY spectrum. This observation can result from H atoms exhibiting a near perpendicular dihedral angle with respect to each other. Although 2D-NMR techniques helped in deciphering the relative stereochemistry, there remained ambiguity with respect to atoms H2A and H3A since there was no correlation found among them in the COSY analysis. A single crystal of this compound was thus prepared and its X-ray diffraction data showed that the H atoms at C2 and C3 were in a perpendicular orientation with respect to each other. The absolute configuration of the molecule was also determined. The present study thus proves unambiguously that the two H atoms are positioned on the tetrahydrofuran ring as depicted in Fig. 7. This observation was helpful in deducing the structural framework of fragment III [see (V) in Fig. 1].
Compound (XII) was crystallized by slow evaporation from a solution in methanol, yielding crystals suitable for single-crystal X-ray diffraction analysis. Compound (XV) is recrystallized by slow evaporation from a solution in a mixture of toluene and n-butanol (7:1 v/v), yielding crystals in the form of colourless prisms ideal for single-crystal X-ray diffraction analysis.
Crystal data, data collection and structure refinement details for (XII) and (XV) are summarized in Table 1. H atoms were placed in geometrically optimized positions and constrained to ride on their parent atoms with C—H = 0.96 (methyl), 0.97 (methylene) and 0.98 Å (methine), and O—H = 0.82 Å for (XII) and C—H = 0.95 (aryl), 0.99 (methylene) and 1.00 Å (methine), and O—H = 0.84 Å for (XV). Displacement parameters for all H atoms were assigned as Uiso(H) = 1.2Ueq(C,O). The orientation of the solvent methyl group in (XII) was allowed to rotate about the C—O bond to find the best fit to the observed electron density peaks and the hydroxy groups in (XV) were similarly allowed to rotate. For (XII), the hydroxy groups at O3 and O9 were also treated this way, but the hydroxy group at O2 was oriented such that the H atom was in a staggered position with respect to the substituents on the parent C atom.
For compound (XII), the relative structure was deduced based on known stereochemistry discussed below, whereas for (XV), the structure was deduced based on the Flack parameter [0.00 (3); Parsons et al., 2013].
For both compounds, data collection: CrystalClear-SM Expert (Rigaku, 2014); cell refinement: CrystalClear-SM Expert (Rigaku, 2014); data reduction: CrystalClear-SM Expert (Rigaku, 2014); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: CrystalStructure (Rigaku, 2015); software used to prepare material for publication: CrystalStructure (Rigaku, 2015).
C19H30O7·CH4O | Dx = 1.296 Mg m−3 |
Mr = 402.48 | Mo Kα radiation, λ = 0.71075 Å |
Orthorhombic, P212121 | Cell parameters from 6335 reflections |
a = 7.2240 (18) Å | θ = 3.2–27.5° |
b = 12.935 (3) Å | µ = 0.10 mm−1 |
c = 22.0691 (10) Å | T = 293 K |
V = 2062.2 (7) Å3 | Prism, colorless |
Z = 4 | 0.20 × 0.20 × 0.20 mm |
F(000) = 872.00 |
Rigaku XtaLAB mini diffractometer | 4568 reflections with F2 > 2.0σ(F2) |
Detector resolution: 13.653 pixels mm-1 | Rint = 0.027 |
ω scans | θmax = 27.5°, θmin = 3.2° |
Absorption correction: numerical (NUMABS; Rigaku, 1999) | h = −9→9 |
Tmin = 0.967, Tmax = 0.980 | k = −16→16 |
20377 measured reflections | l = −28→28 |
4735 independent reflections |
Refinement on F2 | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.037 | H-atom parameters constrained |
wR(F2) = 0.100 | w = 1/[σ2(Fo2) + (0.0514P)2 + 0.2988P] where P = (Fo2 + 2Fc2)/3 |
S = 1.08 | (Δ/σ)max < 0.001 |
4735 reflections | Δρmax = 0.29 e Å−3 |
256 parameters | Δρmin = −0.29 e Å−3 |
0 restraints | Absolute structure: Flack x determined using 1853 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013) |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: 0.0 (3) |
Secondary atom site location: difference Fourier map |
C19H30O7·CH4O | V = 2062.2 (7) Å3 |
Mr = 402.48 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 7.2240 (18) Å | µ = 0.10 mm−1 |
b = 12.935 (3) Å | T = 293 K |
c = 22.0691 (10) Å | 0.20 × 0.20 × 0.20 mm |
Rigaku XtaLAB mini diffractometer | 4735 independent reflections |
Absorption correction: numerical (NUMABS; Rigaku, 1999) | 4568 reflections with F2 > 2.0σ(F2) |
Tmin = 0.967, Tmax = 0.980 | Rint = 0.027 |
20377 measured reflections |
R[F2 > 2σ(F2)] = 0.037 | H-atom parameters constrained |
wR(F2) = 0.100 | Δρmax = 0.29 e Å−3 |
S = 1.08 | Δρmin = −0.29 e Å−3 |
4735 reflections | Absolute structure: Flack x determined using 1853 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013) |
256 parameters | Absolute structure parameter: 0.0 (3) |
0 restraints |
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. |
Refinement. Refinement was performed using all reflections. The weighted R-factor (wR) and goodness of fit (S) are based on F2. R-factor (gt) are based on F. The threshold expression of F2 > 2.0 sigma(F2) is used only for calculating R-factor (gt). Neutral-atom scattering factors were taken from international tables for crystallography, Vol. C, Table 6.1.1.4. Anomalous dispersion effects were included in Fcalc (Ibers & Hamilton, 1964); the values for ?f' and ?f" were extracted from international tables of crystallography (Creagh & McAuley, 1992). The values for the mass attenuation coefficients are those of Creagh and Hubbell. Creagh, D. C. & Hubbell, J.H..; "International Tables for Crystallography", Vol C, (A.J.C. Wilson, ed.), Kluwer Academic Publishers, Boston, Table 4.2.4.3, pages 200-206 (1992). Creagh, D. C. & McAuley, W. J. (1992). International Tables for Crystallography, (A. J. C. Wilson, ed.), Kluwer Academic Publishers, Boston, Vol C, Table 4.2.6.8, 219-222. Ibers, J. A. & Hamilton, W. C. (1964). Acta Cryst. 17, 781–782. |
x | y | z | Uiso*/Ueq | ||
O1 | 0.35295 (19) | 0.58282 (12) | 0.48548 (6) | 0.0371 (3) | |
O2 | 0.3077 (2) | 0.72969 (12) | 0.42698 (7) | 0.0421 (3) | |
H21 | 0.2018 | 0.7108 | 0.4194 | 0.050* | |
O3 | 0.6894 (2) | 0.72168 (11) | 0.39171 (6) | 0.0384 (3) | |
H22 | 0.6789 | 0.7848 | 0.3911 | 0.046* | |
O4 | 0.75860 (19) | 0.51822 (10) | 0.42770 (6) | 0.0311 (3) | |
O5 | 0.6597 (2) | 0.43865 (10) | 0.51248 (7) | 0.0382 (3) | |
O6 | 0.19472 (19) | 0.55968 (11) | 0.60599 (6) | 0.0336 (3) | |
O7 | 0.3195 (2) | 0.46408 (14) | 0.68318 (7) | 0.0471 (4) | |
O8 | 0.5386 (3) | 0.8094 (4) | 0.65156 (10) | 0.1275 (16) | |
H23 | 0.4296 | 0.8074 | 0.6412 | 0.153* | |
C1 | 0.4200 (3) | 0.64349 (14) | 0.43614 (8) | 0.0294 (4) | |
H1 | 0.4191 | 0.6011 | 0.3993 | 0.035* | |
C2 | 0.6160 (3) | 0.68268 (13) | 0.44707 (8) | 0.0283 (4) | |
H2 | 0.6111 | 0.7392 | 0.4766 | 0.034* | |
C3 | 0.7420 (2) | 0.59962 (13) | 0.47104 (8) | 0.0273 (4) | |
H3 | 0.8640 | 0.6284 | 0.4806 | 0.033* | |
C4 | 0.6584 (3) | 0.54600 (13) | 0.52731 (8) | 0.0280 (4) | |
H4 | 0.7365 | 0.5587 | 0.5629 | 0.034* | |
C5 | 0.4611 (3) | 0.58198 (14) | 0.53966 (8) | 0.0279 (4) | |
H5 | 0.4647 | 0.6520 | 0.5565 | 0.033* | |
C6 | 0.3620 (2) | 0.51148 (14) | 0.58383 (8) | 0.0287 (4) | |
H6 | 0.3316 | 0.4459 | 0.5639 | 0.034* | |
C7 | 0.4637 (3) | 0.49056 (17) | 0.64252 (9) | 0.0351 (4) | |
H7A | 0.5508 | 0.4340 | 0.6379 | 0.042* | |
H7B | 0.5297 | 0.5515 | 0.6562 | 0.042* | |
C8 | 0.1523 (3) | 0.51299 (15) | 0.66350 (9) | 0.0331 (4) | |
C9 | 0.0938 (4) | 0.5960 (2) | 0.70757 (11) | 0.0524 (6) | |
H9A | −0.0106 | 0.6337 | 0.6909 | 0.063* | |
H9B | 0.1948 | 0.6444 | 0.7133 | 0.063* | |
C10 | 0.0394 (5) | 0.5495 (2) | 0.76878 (12) | 0.0625 (7) | |
H10A | 0.1474 | 0.5182 | 0.7874 | 0.075* | |
H10B | −0.0039 | 0.6042 | 0.7953 | 0.075* | |
C11 | −0.1116 (4) | 0.4685 (3) | 0.76198 (12) | 0.0617 (7) | |
H11A | −0.1374 | 0.4377 | 0.8011 | 0.074* | |
H11B | −0.2241 | 0.5012 | 0.7476 | 0.074* | |
C12 | −0.0527 (4) | 0.3850 (2) | 0.71778 (12) | 0.0530 (6) | |
H12A | −0.1545 | 0.3372 | 0.7117 | 0.064* | |
H12B | 0.0502 | 0.3466 | 0.7348 | 0.064* | |
C13 | 0.0050 (3) | 0.43058 (18) | 0.65660 (10) | 0.0418 (5) | |
H13A | 0.0519 | 0.3757 | 0.6309 | 0.050* | |
H13B | −0.1026 | 0.4603 | 0.6369 | 0.050* | |
C14 | 0.7801 (3) | 0.42518 (14) | 0.46154 (8) | 0.0305 (4) | |
C15 | 0.7147 (3) | 0.33586 (16) | 0.42330 (11) | 0.0423 (5) | |
H15A | 0.5917 | 0.3507 | 0.4079 | 0.051* | |
H15B | 0.7071 | 0.2742 | 0.4482 | 0.051* | |
C16 | 0.8454 (4) | 0.31621 (18) | 0.37032 (11) | 0.0475 (5) | |
H16A | 0.8046 | 0.2554 | 0.3484 | 0.057* | |
H16B | 0.8408 | 0.3746 | 0.3428 | 0.057* | |
C17 | 1.0433 (4) | 0.3003 (2) | 0.39150 (13) | 0.0526 (6) | |
H17A | 1.1235 | 0.2917 | 0.3566 | 0.063* | |
H17B | 1.0507 | 0.2379 | 0.4158 | 0.063* | |
C18 | 1.1088 (3) | 0.3921 (2) | 0.42881 (12) | 0.0478 (5) | |
H18A | 1.1127 | 0.4532 | 0.4034 | 0.057* | |
H18B | 1.2330 | 0.3789 | 0.4436 | 0.057* | |
C19 | 0.9804 (3) | 0.41131 (17) | 0.48222 (10) | 0.0384 (4) | |
H19A | 1.0204 | 0.4728 | 0.5037 | 0.046* | |
H19B | 0.9877 | 0.3534 | 0.5100 | 0.046* | |
C20 | 0.5497 (5) | 0.8009 (5) | 0.70985 (16) | 0.1046 (17) | |
H20A | 0.5570 | 0.8684 | 0.7277 | 0.126* | |
H20B | 0.6583 | 0.7620 | 0.7203 | 0.126* | |
H20C | 0.4419 | 0.7658 | 0.7249 | 0.126* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0301 (6) | 0.0475 (8) | 0.0337 (7) | −0.0081 (6) | −0.0046 (6) | 0.0125 (6) |
O2 | 0.0391 (8) | 0.0433 (8) | 0.0439 (8) | 0.0115 (7) | −0.0042 (7) | 0.0044 (6) |
O3 | 0.0463 (8) | 0.0315 (6) | 0.0373 (7) | 0.0007 (6) | 0.0088 (7) | 0.0103 (6) |
O4 | 0.0377 (7) | 0.0272 (6) | 0.0283 (6) | 0.0048 (5) | 0.0037 (5) | −0.0007 (5) |
O5 | 0.0444 (8) | 0.0265 (6) | 0.0436 (8) | 0.0037 (6) | 0.0168 (7) | 0.0042 (5) |
O6 | 0.0306 (6) | 0.0381 (7) | 0.0321 (7) | 0.0063 (6) | 0.0068 (6) | 0.0102 (5) |
O7 | 0.0331 (7) | 0.0700 (11) | 0.0382 (8) | 0.0060 (7) | 0.0031 (6) | 0.0235 (8) |
O8 | 0.0373 (10) | 0.296 (5) | 0.0495 (12) | 0.015 (2) | 0.0035 (10) | 0.006 (2) |
C1 | 0.0320 (9) | 0.0305 (8) | 0.0257 (8) | 0.0019 (7) | −0.0004 (7) | 0.0011 (7) |
C2 | 0.0324 (9) | 0.0241 (8) | 0.0284 (8) | −0.0005 (7) | 0.0029 (7) | 0.0015 (6) |
C3 | 0.0261 (8) | 0.0267 (8) | 0.0291 (8) | −0.0006 (7) | 0.0005 (7) | −0.0013 (7) |
C4 | 0.0295 (8) | 0.0280 (8) | 0.0266 (8) | 0.0014 (7) | 0.0000 (7) | 0.0005 (6) |
C5 | 0.0283 (8) | 0.0279 (8) | 0.0273 (8) | 0.0002 (7) | 0.0017 (7) | 0.0012 (7) |
C6 | 0.0271 (8) | 0.0297 (8) | 0.0292 (8) | −0.0003 (7) | 0.0036 (7) | 0.0022 (7) |
C7 | 0.0291 (9) | 0.0412 (10) | 0.0352 (9) | 0.0028 (8) | 0.0016 (8) | 0.0062 (8) |
C8 | 0.0313 (9) | 0.0379 (9) | 0.0302 (9) | 0.0032 (8) | 0.0048 (7) | 0.0088 (7) |
C9 | 0.0696 (17) | 0.0458 (12) | 0.0418 (12) | −0.0032 (12) | 0.0181 (12) | −0.0015 (10) |
C10 | 0.0811 (19) | 0.0695 (17) | 0.0369 (12) | −0.0062 (15) | 0.0208 (13) | −0.0041 (11) |
C11 | 0.0542 (14) | 0.088 (2) | 0.0426 (12) | −0.0018 (14) | 0.0173 (12) | 0.0176 (13) |
C12 | 0.0490 (13) | 0.0579 (15) | 0.0521 (13) | −0.0116 (11) | 0.0022 (11) | 0.0207 (11) |
C13 | 0.0395 (11) | 0.0465 (11) | 0.0396 (11) | −0.0043 (9) | 0.0002 (9) | 0.0080 (9) |
C14 | 0.0331 (9) | 0.0267 (8) | 0.0319 (9) | 0.0023 (7) | 0.0051 (7) | 0.0025 (7) |
C15 | 0.0408 (11) | 0.0328 (10) | 0.0534 (12) | −0.0055 (8) | 0.0008 (10) | −0.0082 (9) |
C16 | 0.0569 (14) | 0.0408 (11) | 0.0450 (12) | −0.0035 (11) | 0.0005 (11) | −0.0151 (9) |
C17 | 0.0536 (14) | 0.0463 (13) | 0.0581 (15) | 0.0107 (11) | 0.0114 (12) | −0.0125 (11) |
C18 | 0.0335 (10) | 0.0513 (13) | 0.0585 (14) | 0.0060 (9) | 0.0055 (10) | −0.0108 (11) |
C19 | 0.0373 (10) | 0.0378 (10) | 0.0401 (10) | 0.0094 (8) | −0.0041 (9) | −0.0040 (8) |
C20 | 0.0575 (19) | 0.192 (5) | 0.064 (2) | −0.003 (3) | −0.0071 (17) | −0.044 (3) |
O1—C1 | 1.427 (2) | C9—H9A | 0.9700 |
O1—C5 | 1.428 (2) | C9—H9B | 0.9700 |
O2—C1 | 1.394 (2) | C10—C11 | 1.520 (4) |
O2—H21 | 0.8200 | C10—H10A | 0.9700 |
O3—C2 | 1.424 (2) | C10—H10B | 0.9700 |
O3—H22 | 0.8200 | C11—C12 | 1.517 (4) |
O4—C14 | 1.425 (2) | C11—H11A | 0.9700 |
O4—C3 | 1.428 (2) | C11—H11B | 0.9700 |
O5—C4 | 1.427 (2) | C12—C13 | 1.531 (3) |
O5—C14 | 1.432 (2) | C12—H12A | 0.9700 |
O6—C8 | 1.439 (2) | C12—H12B | 0.9700 |
O6—C6 | 1.445 (2) | C13—H13A | 0.9700 |
O7—C7 | 1.417 (2) | C13—H13B | 0.9700 |
O7—C8 | 1.431 (2) | C14—C15 | 1.507 (3) |
O8—C20 | 1.294 (4) | C14—C19 | 1.528 (3) |
O8—H23 | 0.8200 | C15—C16 | 1.524 (3) |
C1—C2 | 1.523 (3) | C15—H15A | 0.9700 |
C1—H1 | 0.9800 | C15—H15B | 0.9700 |
C2—C3 | 1.504 (2) | C16—C17 | 1.518 (4) |
C2—H2 | 0.9800 | C16—H16A | 0.9700 |
C3—C4 | 1.545 (2) | C16—H16B | 0.9700 |
C3—H3 | 0.9800 | C17—C18 | 1.520 (3) |
C4—C5 | 1.524 (3) | C17—H17A | 0.9700 |
C4—H4 | 0.9800 | C17—H17B | 0.9700 |
C5—C6 | 1.515 (2) | C18—C19 | 1.520 (3) |
C5—H5 | 0.9800 | C18—H18A | 0.9700 |
C6—C7 | 1.513 (3) | C18—H18B | 0.9700 |
C6—H6 | 0.9800 | C19—H19A | 0.9700 |
C7—H7A | 0.9700 | C19—H19B | 0.9700 |
C7—H7B | 0.9700 | C20—H20A | 0.9600 |
C8—C9 | 1.509 (3) | C20—H20B | 0.9600 |
C8—C13 | 1.514 (3) | C20—H20C | 0.9600 |
C9—C10 | 1.530 (3) | ||
C1—O1—C5 | 117.22 (14) | C9—C10—H10A | 109.3 |
C1—O2—H21 | 109.5 | C11—C10—H10B | 109.3 |
C2—O3—H22 | 109.5 | C9—C10—H10B | 109.3 |
C14—O4—C3 | 106.31 (13) | H10A—C10—H10B | 108.0 |
C4—O5—C14 | 107.60 (14) | C12—C11—C10 | 110.7 (2) |
C8—O6—C6 | 107.20 (13) | C12—C11—H11A | 109.5 |
C7—O7—C8 | 108.75 (14) | C10—C11—H11A | 109.5 |
C20—O8—H23 | 109.5 | C12—C11—H11B | 109.5 |
O2—C1—O1 | 110.68 (15) | C10—C11—H11B | 109.5 |
O2—C1—C2 | 107.32 (16) | H11A—C11—H11B | 108.1 |
O1—C1—C2 | 112.19 (15) | C11—C12—C13 | 111.6 (2) |
O2—C1—H1 | 108.9 | C11—C12—H12A | 109.3 |
O1—C1—H1 | 108.9 | C13—C12—H12A | 109.3 |
C2—C1—H1 | 108.9 | C11—C12—H12B | 109.3 |
O3—C2—C3 | 109.24 (15) | C13—C12—H12B | 109.3 |
O3—C2—C1 | 109.16 (15) | H12A—C12—H12B | 108.0 |
C3—C2—C1 | 112.36 (15) | C8—C13—C12 | 111.97 (19) |
O3—C2—H2 | 108.7 | C8—C13—H13A | 109.2 |
C3—C2—H2 | 108.7 | C12—C13—H13A | 109.2 |
C1—C2—H2 | 108.7 | C8—C13—H13B | 109.2 |
O4—C3—C2 | 110.01 (14) | C12—C13—H13B | 109.2 |
O4—C3—C4 | 103.90 (13) | H13A—C13—H13B | 107.9 |
C2—C3—C4 | 111.54 (15) | O4—C14—O5 | 104.05 (14) |
O4—C3—H3 | 110.4 | O4—C14—C15 | 108.65 (16) |
C2—C3—H3 | 110.4 | O5—C14—C15 | 110.03 (17) |
C4—C3—H3 | 110.4 | O4—C14—C19 | 111.03 (16) |
O5—C4—C5 | 110.13 (15) | O5—C14—C19 | 110.79 (16) |
O5—C4—C3 | 104.48 (14) | C15—C14—C19 | 111.98 (17) |
C5—C4—C3 | 111.83 (14) | C14—C15—C16 | 111.30 (18) |
O5—C4—H4 | 110.1 | C14—C15—H15A | 109.4 |
C5—C4—H4 | 110.1 | C16—C15—H15A | 109.4 |
C3—C4—H4 | 110.1 | C14—C15—H15B | 109.4 |
O1—C5—C6 | 106.55 (15) | C16—C15—H15B | 109.4 |
O1—C5—C4 | 111.36 (14) | H15A—C15—H15B | 108.0 |
C6—C5—C4 | 111.91 (15) | C17—C16—C15 | 111.7 (2) |
O1—C5—H5 | 109.0 | C17—C16—H16A | 109.3 |
C6—C5—H5 | 109.0 | C15—C16—H16A | 109.3 |
C4—C5—H5 | 109.0 | C17—C16—H16B | 109.3 |
O6—C6—C7 | 101.16 (14) | C15—C16—H16B | 109.3 |
O6—C6—C5 | 110.69 (14) | H16A—C16—H16B | 107.9 |
C7—C6—C5 | 115.41 (16) | C16—C17—C18 | 110.74 (19) |
O6—C6—H6 | 109.8 | C16—C17—H17A | 109.5 |
C7—C6—H6 | 109.8 | C18—C17—H17A | 109.5 |
C5—C6—H6 | 109.8 | C16—C17—H17B | 109.5 |
O7—C7—C6 | 103.20 (15) | C18—C17—H17B | 109.5 |
O7—C7—H7A | 111.1 | H17A—C17—H17B | 108.1 |
C6—C7—H7A | 111.1 | C17—C18—C19 | 111.0 (2) |
O7—C7—H7B | 111.1 | C17—C18—H18A | 109.4 |
C6—C7—H7B | 111.1 | C19—C18—H18A | 109.4 |
H7A—C7—H7B | 109.1 | C17—C18—H18B | 109.4 |
O7—C8—O6 | 105.87 (14) | C19—C18—H18B | 109.4 |
O7—C8—C9 | 110.8 (2) | H18A—C18—H18B | 108.0 |
O6—C8—C9 | 109.25 (17) | C18—C19—C14 | 111.43 (18) |
O7—C8—C13 | 108.20 (17) | C18—C19—H19A | 109.3 |
O6—C8—C13 | 110.89 (16) | C14—C19—H19A | 109.3 |
C9—C8—C13 | 111.64 (18) | C18—C19—H19B | 109.3 |
C8—C9—C10 | 111.2 (2) | C14—C19—H19B | 109.3 |
C8—C9—H9A | 109.4 | H19A—C19—H19B | 108.0 |
C10—C9—H9A | 109.4 | O8—C20—H20A | 109.5 |
C8—C9—H9B | 109.4 | O8—C20—H20B | 109.5 |
C10—C9—H9B | 109.4 | H20A—C20—H20B | 109.5 |
H9A—C9—H9B | 108.0 | O8—C20—H20C | 109.5 |
C11—C10—C9 | 111.6 (2) | H20A—C20—H20C | 109.5 |
C11—C10—H10A | 109.3 | H20B—C20—H20C | 109.5 |
C5—O1—C1—O2 | −109.98 (18) | C7—O7—C8—O6 | 6.6 (2) |
C5—O1—C1—C2 | 9.9 (2) | C7—O7—C8—C9 | −111.7 (2) |
O2—C1—C2—O3 | −71.31 (18) | C7—O7—C8—C13 | 125.54 (17) |
O1—C1—C2—O3 | 166.90 (15) | C6—O6—C8—O7 | 17.8 (2) |
O2—C1—C2—C3 | 167.35 (14) | C6—O6—C8—C9 | 137.22 (19) |
O1—C1—C2—C3 | 45.6 (2) | C6—O6—C8—C13 | −99.31 (18) |
C14—O4—C3—C2 | −147.13 (15) | O7—C8—C9—C10 | −66.1 (3) |
C14—O4—C3—C4 | −27.62 (17) | O6—C8—C9—C10 | 177.7 (2) |
O3—C2—C3—O4 | −58.95 (19) | C13—C8—C9—C10 | 54.6 (3) |
C1—C2—C3—O4 | 62.34 (19) | C8—C9—C10—C11 | −55.9 (3) |
O3—C2—C3—C4 | −173.70 (14) | C9—C10—C11—C12 | 55.7 (3) |
C1—C2—C3—C4 | −52.4 (2) | C10—C11—C12—C13 | −54.5 (3) |
C14—O5—C4—C5 | 135.78 (16) | O7—C8—C13—C12 | 68.4 (2) |
C14—O5—C4—C3 | 15.54 (19) | O6—C8—C13—C12 | −175.94 (19) |
O4—C3—C4—O5 | 7.32 (18) | C9—C8—C13—C12 | −53.9 (3) |
C2—C3—C4—O5 | 125.79 (16) | C11—C12—C13—C8 | 53.9 (3) |
O4—C3—C4—C5 | −111.78 (16) | C3—O4—C14—O5 | 37.86 (18) |
C2—C3—C4—C5 | 6.7 (2) | C3—O4—C14—C15 | 155.06 (16) |
C1—O1—C5—C6 | −179.18 (15) | C3—O4—C14—C19 | −81.37 (18) |
C1—O1—C5—C4 | −56.9 (2) | C4—O5—C14—O4 | −32.95 (19) |
O5—C4—C5—O1 | −69.48 (18) | C4—O5—C14—C15 | −149.19 (17) |
C3—C4—C5—O1 | 46.22 (19) | C4—O5—C14—C19 | 86.43 (18) |
O5—C4—C5—C6 | 49.67 (19) | O4—C14—C15—C16 | 69.4 (2) |
C3—C4—C5—C6 | 165.37 (15) | O5—C14—C15—C16 | −177.24 (18) |
C8—O6—C6—C7 | −33.24 (18) | C19—C14—C15—C16 | −53.6 (2) |
C8—O6—C6—C5 | −156.06 (16) | C14—C15—C16—C17 | 54.8 (3) |
O1—C5—C6—O6 | −71.94 (18) | C15—C16—C17—C18 | −56.1 (3) |
C4—C5—C6—O6 | 166.11 (14) | C16—C17—C18—C19 | 56.3 (3) |
O1—C5—C6—C7 | 173.96 (15) | C17—C18—C19—C14 | −55.2 (3) |
C4—C5—C6—C7 | 52.0 (2) | O4—C14—C19—C18 | −67.5 (2) |
C8—O7—C7—C6 | −26.9 (2) | O5—C14—C19—C18 | 177.44 (17) |
O6—C6—C7—O7 | 36.38 (19) | C15—C14—C19—C18 | 54.2 (2) |
C5—C6—C7—O7 | 155.87 (16) |
D—H···A | D—H | H···A | D···A | D—H···A |
O2—H21···O8i | 0.82 | 1.98 | 2.653 (3) | 139 |
O3—H22···O6ii | 0.82 | 2.02 | 2.829 (2) | 171 |
O8—H23···O3i | 0.82 | 1.92 | 2.727 (3) | 169 |
Symmetry codes: (i) x−1/2, −y+3/2, −z+1; (ii) x+1/2, −y+3/2, −z+1. |
C17H24O6S | Dx = 1.367 Mg m−3 |
Mr = 356.43 | Mo Kα radiation, λ = 0.71075 Å |
Orthorhombic, P212121 | Cell parameters from 4380 reflections |
a = 7.593 (6) Å | θ = 3.1–27.5° |
b = 8.542 (7) Å | µ = 0.22 mm−1 |
c = 26.70 (2) Å | T = 200 K |
V = 1732 (2) Å3 | Prism, colorless |
Z = 4 | 0.40 × 0.32 × 0.20 mm |
F(000) = 760.00 |
Rigaku XtaLAB mini diffractometer | 3733 reflections with F2 > 2.0σ(F2) |
Detector resolution: 13.653 pixels mm-1 | Rint = 0.034 |
ω scans | θmax = 27.5°, θmin = 3.1° |
Absorption correction: numerical (NUMABS; Rigaku, 1999) | h = −9→9 |
Tmin = 0.887, Tmax = 0.958 | k = −11→11 |
14279 measured reflections | l = −34→34 |
3942 independent reflections |
Refinement on F2 | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.033 | H-atom parameters constrained |
wR(F2) = 0.082 | w = 1/[σ2(Fo2) + (0.0405P)2 + 0.1659P] where P = (Fo2 + 2Fc2)/3 |
S = 1.05 | (Δ/σ)max = 0.002 |
3942 reflections | Δρmax = 0.23 e Å−3 |
220 parameters | Δρmin = −0.24 e Å−3 |
0 restraints | Absolute structure: Flack x determined using 1454 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013) |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: 0.00 (3) |
Secondary atom site location: difference Fourier map |
C17H24O6S | V = 1732 (2) Å3 |
Mr = 356.43 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 7.593 (6) Å | µ = 0.22 mm−1 |
b = 8.542 (7) Å | T = 200 K |
c = 26.70 (2) Å | 0.40 × 0.32 × 0.20 mm |
Rigaku XtaLAB mini diffractometer | 3942 independent reflections |
Absorption correction: numerical (NUMABS; Rigaku, 1999) | 3733 reflections with F2 > 2.0σ(F2) |
Tmin = 0.887, Tmax = 0.958 | Rint = 0.034 |
14279 measured reflections |
R[F2 > 2σ(F2)] = 0.033 | H-atom parameters constrained |
wR(F2) = 0.082 | Δρmax = 0.23 e Å−3 |
S = 1.05 | Δρmin = −0.24 e Å−3 |
3942 reflections | Absolute structure: Flack x determined using 1454 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013) |
220 parameters | Absolute structure parameter: 0.00 (3) |
0 restraints |
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. |
Refinement. Refinement was performed using all reflections. The weighted R-factor (wR) and goodness of fit (S) are based on F2. R-factor (gt) are based on F. The threshold expression of F2 > 2.0 sigma(F2) is used only for calculating R-factor (gt). Neutral-atom scattering factors were taken from international tables for crystallography, Vol. C, Table 6.1.1.4. Anomalous dispersion effects were included in Fcalc (Ibers & Hamilton, 1964); the values for ?f' and ?f" were extracted from international tables of crystallography (Creagh & McAuley, 1992). The values for the mass attenuation coefficients are those of Creagh and Hubbell. Creagh, D. C. & Hubbell, J.H..; "International Tables for Crystallography", Vol C, (A.J.C. Wilson, ed.), Kluwer Academic Publishers, Boston, Table 4.2.4.3, pages 200-206 (1992). Creagh, D. C. & McAuley, W. J. (1992). International Tables for Crystallography, (A. J. C. Wilson, ed.), Kluwer Academic Publishers, Boston, Vol C, Table 4.2.6.8, 219-222. Ibers, J. A. & Hamilton, W. C. (1964). Acta Cryst. 17, 781–782. |
x | y | z | Uiso*/Ueq | ||
S1 | 0.75191 (7) | 0.69616 (6) | 0.55350 (2) | 0.03182 (14) | |
O1 | 0.26736 (18) | 0.69593 (16) | 0.68646 (5) | 0.0270 (3) | |
O2 | −0.16817 (19) | 0.34917 (19) | 0.72260 (6) | 0.0327 (4) | |
H18 | −0.1726 | 0.3074 | 0.7511 | 0.039* | |
O3 | 0.1105 (2) | 0.3635 (2) | 0.79208 (5) | 0.0328 (4) | |
H19 | 0.1752 | 0.2837 | 0.7923 | 0.039* | |
O4 | 0.64460 (18) | 0.61630 (18) | 0.70728 (5) | 0.0284 (3) | |
H20 | 0.7053 | 0.5376 | 0.7149 | 0.034* | |
O5 | 0.8699 (2) | 0.6311 (2) | 0.58990 (7) | 0.0467 (5) | |
O6 | 0.7510 (3) | 0.6297 (2) | 0.50392 (6) | 0.0502 (5) | |
C1 | 0.3456 (3) | 0.5447 (2) | 0.68089 (7) | 0.0241 (4) | |
H1 | 0.2854 | 0.4884 | 0.6528 | 0.029* | |
C2 | 0.5358 (2) | 0.5797 (2) | 0.66544 (7) | 0.0221 (4) | |
H2 | 0.5864 | 0.4906 | 0.6458 | 0.027* | |
C3 | 0.5122 (2) | 0.7255 (2) | 0.63198 (7) | 0.0228 (4) | |
H3 | 0.5996 | 0.8075 | 0.6418 | 0.027* | |
C4 | 0.3228 (3) | 0.7839 (2) | 0.64351 (7) | 0.0251 (4) | |
H4 | 0.2441 | 0.7590 | 0.6145 | 0.030* | |
C5 | 0.3185 (3) | 0.4530 (3) | 0.72883 (8) | 0.0277 (4) | |
H5A | 0.3862 | 0.5039 | 0.7560 | 0.033* | |
H5B | 0.3664 | 0.3462 | 0.7243 | 0.033* | |
C6 | 0.1256 (3) | 0.4405 (2) | 0.74488 (7) | 0.0247 (4) | |
H6 | 0.0794 | 0.5494 | 0.7491 | 0.030* | |
C7 | 0.0107 (3) | 0.3587 (3) | 0.70659 (8) | 0.0299 (4) | |
H7A | 0.0164 | 0.4163 | 0.6745 | 0.036* | |
H7B | 0.0565 | 0.2517 | 0.7008 | 0.036* | |
C8 | 0.5323 (3) | 0.6877 (3) | 0.57634 (7) | 0.0280 (4) | |
H8A | 0.4594 | 0.7621 | 0.5569 | 0.034* | |
H8B | 0.4854 | 0.5813 | 0.5702 | 0.034* | |
C9 | 0.3069 (3) | 0.9562 (2) | 0.65609 (8) | 0.0292 (4) | |
H9A | 0.1841 | 0.9789 | 0.6662 | 0.035* | |
H9B | 0.3842 | 0.9801 | 0.6850 | 0.035* | |
C10 | 0.3560 (3) | 1.0602 (3) | 0.61316 (9) | 0.0350 (5) | |
H10 | 0.2976 | 1.0449 | 0.5821 | 0.042* | |
C11 | 0.4748 (4) | 1.1710 (3) | 0.61602 (10) | 0.0475 (6) | |
H11A | 0.5353 | 1.1889 | 0.6466 | 0.057* | |
H11B | 0.5004 | 1.2334 | 0.5875 | 0.057* | |
C12 | 0.7918 (3) | 0.8995 (3) | 0.54793 (8) | 0.0309 (5) | |
C13 | 0.8810 (3) | 0.9767 (3) | 0.58547 (10) | 0.0416 (6) | |
H13 | 0.9228 | 0.9217 | 0.6140 | 0.050* | |
C14 | 0.9085 (4) | 1.1358 (4) | 0.58069 (13) | 0.0564 (7) | |
H14 | 0.9690 | 1.1911 | 0.6063 | 0.068* | |
C15 | 0.8489 (4) | 1.2146 (4) | 0.53927 (14) | 0.0605 (9) | |
H15 | 0.8698 | 1.3238 | 0.5362 | 0.073* | |
C16 | 0.7584 (4) | 1.1360 (3) | 0.50181 (12) | 0.0529 (7) | |
H16 | 0.7167 | 1.1915 | 0.4733 | 0.064* | |
C17 | 0.7289 (3) | 0.9771 (3) | 0.50593 (9) | 0.0386 (5) | |
H17 | 0.6669 | 0.9220 | 0.4805 | 0.046* |
U11 | U22 | U33 | U12 | U13 | U23 | |
S1 | 0.0310 (3) | 0.0329 (3) | 0.0315 (3) | 0.0026 (2) | 0.0104 (2) | 0.0010 (2) |
O1 | 0.0278 (7) | 0.0240 (7) | 0.0293 (6) | 0.0051 (7) | 0.0081 (6) | 0.0045 (5) |
O2 | 0.0242 (7) | 0.0388 (9) | 0.0351 (8) | −0.0017 (6) | 0.0005 (6) | 0.0113 (6) |
O3 | 0.0306 (8) | 0.0414 (9) | 0.0263 (7) | 0.0036 (7) | 0.0059 (6) | 0.0081 (6) |
O4 | 0.0253 (7) | 0.0307 (8) | 0.0292 (7) | 0.0008 (6) | −0.0051 (6) | 0.0030 (6) |
O5 | 0.0337 (9) | 0.0484 (10) | 0.0582 (11) | 0.0123 (8) | 0.0058 (8) | 0.0165 (9) |
O6 | 0.0644 (11) | 0.0472 (10) | 0.0389 (9) | −0.0066 (10) | 0.0241 (10) | −0.0119 (7) |
C1 | 0.0240 (9) | 0.0223 (10) | 0.0259 (9) | 0.0003 (8) | 0.0020 (7) | 0.0009 (7) |
C2 | 0.0217 (9) | 0.0218 (10) | 0.0228 (9) | 0.0013 (7) | 0.0018 (7) | −0.0001 (7) |
C3 | 0.0211 (8) | 0.0236 (10) | 0.0238 (9) | −0.0001 (8) | 0.0012 (7) | 0.0011 (7) |
C4 | 0.0225 (9) | 0.0284 (11) | 0.0244 (9) | 0.0016 (8) | 0.0015 (7) | 0.0031 (8) |
C5 | 0.0228 (9) | 0.0301 (11) | 0.0301 (10) | 0.0014 (8) | 0.0027 (8) | 0.0074 (8) |
C6 | 0.0255 (9) | 0.0225 (10) | 0.0261 (9) | 0.0010 (8) | 0.0037 (8) | 0.0046 (8) |
C7 | 0.0261 (9) | 0.0348 (12) | 0.0289 (10) | −0.0030 (9) | 0.0041 (8) | 0.0015 (8) |
C8 | 0.0250 (9) | 0.0356 (11) | 0.0233 (9) | −0.0028 (9) | 0.0017 (7) | 0.0019 (9) |
C9 | 0.0298 (10) | 0.0264 (11) | 0.0315 (10) | 0.0042 (8) | 0.0017 (8) | 0.0019 (8) |
C10 | 0.0398 (12) | 0.0289 (12) | 0.0364 (11) | 0.0082 (10) | 0.0049 (10) | 0.0042 (9) |
C11 | 0.0582 (16) | 0.0312 (13) | 0.0531 (15) | −0.0015 (12) | 0.0139 (13) | 0.0030 (11) |
C12 | 0.0246 (9) | 0.0372 (12) | 0.0311 (10) | 0.0003 (9) | 0.0066 (8) | 0.0015 (9) |
C13 | 0.0338 (12) | 0.0479 (15) | 0.0432 (13) | −0.0022 (11) | −0.0006 (10) | −0.0030 (11) |
C14 | 0.0419 (14) | 0.0501 (17) | 0.077 (2) | −0.0097 (14) | 0.0021 (14) | −0.0164 (15) |
C15 | 0.0414 (14) | 0.0361 (15) | 0.104 (3) | −0.0017 (13) | 0.0187 (16) | 0.0052 (16) |
C16 | 0.0389 (13) | 0.0508 (16) | 0.0691 (17) | 0.0089 (13) | 0.0140 (14) | 0.0251 (14) |
C17 | 0.0317 (12) | 0.0471 (14) | 0.0370 (11) | 0.0027 (11) | 0.0055 (10) | 0.0073 (10) |
S1—O5 | 1.4339 (19) | C6—C7 | 1.515 (3) |
S1—O6 | 1.4403 (19) | C6—H6 | 1.0000 |
S1—C12 | 1.769 (3) | C7—H7A | 0.9900 |
S1—C8 | 1.777 (2) | C7—H7B | 0.9900 |
O1—C1 | 1.430 (3) | C8—H8A | 0.9900 |
O1—C4 | 1.434 (2) | C8—H8B | 0.9900 |
O2—C7 | 1.426 (3) | C9—C10 | 1.497 (3) |
O2—H18 | 0.8400 | C9—H9A | 0.9900 |
O3—C6 | 1.426 (2) | C9—H9B | 0.9900 |
O3—H19 | 0.8400 | C10—C11 | 1.310 (4) |
O4—C2 | 1.424 (2) | C10—H10 | 0.9500 |
O4—H20 | 0.8400 | C11—H11A | 0.9500 |
C1—C5 | 1.514 (3) | C11—H11B | 0.9500 |
C1—C2 | 1.531 (3) | C12—C13 | 1.378 (3) |
C1—H1 | 1.0000 | C12—C17 | 1.388 (3) |
C2—C3 | 1.543 (3) | C13—C14 | 1.381 (4) |
C2—H2 | 1.0000 | C13—H13 | 0.9500 |
C3—C8 | 1.528 (3) | C14—C15 | 1.371 (5) |
C3—C4 | 1.554 (3) | C14—H14 | 0.9500 |
C3—H3 | 1.0000 | C15—C16 | 1.387 (5) |
C4—C9 | 1.514 (3) | C15—H15 | 0.9500 |
C4—H4 | 1.0000 | C16—C17 | 1.380 (4) |
C5—C6 | 1.530 (3) | C16—H16 | 0.9500 |
C5—H5A | 0.9900 | C17—H17 | 0.9500 |
C5—H5B | 0.9900 | ||
O5—S1—O6 | 118.24 (13) | C7—C6—H6 | 107.6 |
O5—S1—C12 | 109.31 (11) | C5—C6—H6 | 107.6 |
O6—S1—C12 | 108.07 (11) | O2—C7—C6 | 111.86 (17) |
O5—S1—C8 | 109.73 (11) | O2—C7—H7A | 109.2 |
O6—S1—C8 | 107.17 (12) | C6—C7—H7A | 109.2 |
C12—S1—C8 | 103.27 (10) | O2—C7—H7B | 109.2 |
C1—O1—C4 | 105.59 (14) | C6—C7—H7B | 109.2 |
C7—O2—H18 | 109.5 | H7A—C7—H7B | 107.9 |
C6—O3—H19 | 109.5 | C3—C8—S1 | 114.77 (14) |
C2—O4—H20 | 109.5 | C3—C8—H8A | 108.6 |
O1—C1—C5 | 108.84 (16) | S1—C8—H8A | 108.6 |
O1—C1—C2 | 104.07 (16) | C3—C8—H8B | 108.6 |
C5—C1—C2 | 117.17 (16) | S1—C8—H8B | 108.6 |
O1—C1—H1 | 108.8 | H8A—C8—H8B | 107.5 |
C5—C1—H1 | 108.8 | C10—C9—C4 | 112.76 (18) |
C2—C1—H1 | 108.8 | C10—C9—H9A | 109.0 |
O4—C2—C1 | 112.26 (16) | C4—C9—H9A | 109.0 |
O4—C2—C3 | 110.11 (16) | C10—C9—H9B | 109.0 |
C1—C2—C3 | 101.79 (15) | C4—C9—H9B | 109.0 |
O4—C2—H2 | 110.8 | H9A—C9—H9B | 107.8 |
C1—C2—H2 | 110.8 | C11—C10—C9 | 123.7 (2) |
C3—C2—H2 | 110.8 | C11—C10—H10 | 118.1 |
C8—C3—C2 | 112.39 (17) | C9—C10—H10 | 118.1 |
C8—C3—C4 | 110.67 (16) | C10—C11—H11A | 120.0 |
C2—C3—C4 | 104.60 (15) | C10—C11—H11B | 120.0 |
C8—C3—H3 | 109.7 | H11A—C11—H11B | 120.0 |
C2—C3—H3 | 109.7 | C13—C12—C17 | 121.9 (2) |
C4—C3—H3 | 109.7 | C13—C12—S1 | 119.54 (19) |
O1—C4—C9 | 107.97 (16) | C17—C12—S1 | 118.57 (18) |
O1—C4—C3 | 105.16 (15) | C12—C13—C14 | 118.6 (3) |
C9—C4—C3 | 115.47 (17) | C12—C13—H13 | 120.7 |
O1—C4—H4 | 109.3 | C14—C13—H13 | 120.7 |
C9—C4—H4 | 109.3 | C15—C14—C13 | 120.5 (3) |
C3—C4—H4 | 109.3 | C15—C14—H14 | 119.7 |
C1—C5—C6 | 113.76 (16) | C13—C14—H14 | 119.7 |
C1—C5—H5A | 108.8 | C14—C15—C16 | 120.5 (3) |
C6—C5—H5A | 108.8 | C14—C15—H15 | 119.7 |
C1—C5—H5B | 108.8 | C16—C15—H15 | 119.7 |
C6—C5—H5B | 108.8 | C17—C16—C15 | 119.9 (3) |
H5A—C5—H5B | 107.7 | C17—C16—H16 | 120.0 |
O3—C6—C7 | 109.69 (17) | C15—C16—H16 | 120.0 |
O3—C6—C5 | 110.90 (15) | C16—C17—C12 | 118.6 (2) |
C7—C6—C5 | 113.23 (17) | C16—C17—H17 | 120.7 |
O3—C6—H6 | 107.6 | C12—C17—H17 | 120.7 |
C4—O1—C1—C5 | 170.74 (15) | C2—C3—C8—S1 | −87.49 (19) |
C4—O1—C1—C2 | 45.09 (18) | C4—C3—C8—S1 | 155.97 (15) |
O1—C1—C2—O4 | 81.59 (18) | O5—S1—C8—C3 | 39.8 (2) |
C5—C1—C2—O4 | −38.6 (2) | O6—S1—C8—C3 | 169.40 (16) |
O1—C1—C2—C3 | −36.12 (18) | C12—S1—C8—C3 | −76.62 (18) |
C5—C1—C2—C3 | −156.31 (17) | O1—C4—C9—C10 | −178.13 (17) |
O4—C2—C3—C8 | 135.57 (17) | C3—C4—C9—C10 | 64.6 (2) |
C1—C2—C3—C8 | −105.19 (17) | C4—C9—C10—C11 | −125.5 (3) |
O4—C2—C3—C4 | −104.31 (17) | O5—S1—C12—C13 | −18.8 (2) |
C1—C2—C3—C4 | 14.93 (19) | O6—S1—C12—C13 | −148.67 (19) |
C1—O1—C4—C9 | −158.33 (16) | C8—S1—C12—C13 | 98.00 (19) |
C1—O1—C4—C3 | −34.53 (19) | O5—S1—C12—C17 | 162.38 (17) |
C8—C3—C4—O1 | 131.96 (18) | O6—S1—C12—C17 | 32.5 (2) |
C2—C3—C4—O1 | 10.70 (19) | C8—S1—C12—C17 | −80.87 (19) |
C8—C3—C4—C9 | −109.15 (19) | C17—C12—C13—C14 | −0.2 (4) |
C2—C3—C4—C9 | 129.58 (18) | S1—C12—C13—C14 | −179.1 (2) |
O1—C1—C5—C6 | 55.3 (2) | C12—C13—C14—C15 | −0.4 (4) |
C2—C1—C5—C6 | 172.89 (17) | C13—C14—C15—C16 | 0.8 (4) |
C1—C5—C6—O3 | −175.56 (17) | C14—C15—C16—C17 | −0.5 (4) |
C1—C5—C6—C7 | 60.6 (2) | C15—C16—C17—C12 | −0.1 (4) |
O3—C6—C7—O2 | 55.6 (2) | C13—C12—C17—C16 | 0.5 (3) |
C5—C6—C7—O2 | −179.89 (16) | S1—C12—C17—C16 | 179.33 (18) |
D—H···A | D—H | H···A | D···A | D—H···A |
O2—H18···O1i | 0.84 | 2.05 | 2.859 (3) | 161 |
O2—H18···O3 | 0.84 | 2.46 | 2.817 (3) | 107 |
O3—H19···O4ii | 0.84 | 1.98 | 2.813 (3) | 172 |
O4—H20···O2iii | 0.84 | 1.89 | 2.719 (3) | 171 |
Symmetry codes: (i) −x, y−1/2, −z+3/2; (ii) −x+1, y−1/2, −z+3/2; (iii) x+1, y, z. |
Experimental details
(Comp_XII) | (Comp_XV) | |
Crystal data | ||
Chemical formula | C19H30O7·CH4O | C17H24O6S |
Mr | 402.48 | 356.43 |
Crystal system, space group | Orthorhombic, P212121 | Orthorhombic, P212121 |
Temperature (K) | 293 | 200 |
a, b, c (Å) | 7.2240 (18), 12.935 (3), 22.0691 (10) | 7.593 (6), 8.542 (7), 26.70 (2) |
V (Å3) | 2062.2 (7) | 1732 (2) |
Z | 4 | 4 |
Radiation type | Mo Kα | Mo Kα |
µ (mm−1) | 0.10 | 0.22 |
Crystal size (mm) | 0.20 × 0.20 × 0.20 | 0.40 × 0.32 × 0.20 |
Data collection | ||
Diffractometer | Rigaku XtaLAB mini | Rigaku XtaLAB mini |
Absorption correction | Numerical (NUMABS; Rigaku, 1999) | Numerical (NUMABS; Rigaku, 1999) |
Tmin, Tmax | 0.967, 0.980 | 0.887, 0.958 |
No. of measured, independent and observed [F2 > 2.0σ(F2)] reflections | 20377, 4735, 4568 | 14279, 3942, 3733 |
Rint | 0.027 | 0.034 |
(sin θ/λ)max (Å−1) | 0.649 | 0.650 |
Refinement | ||
R[F2 > 2σ(F2)], wR(F2), S | 0.037, 0.100, 1.08 | 0.033, 0.082, 1.05 |
No. of reflections | 4735 | 3942 |
No. of parameters | 256 | 220 |
H-atom treatment | H-atom parameters constrained | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.29, −0.29 | 0.23, −0.24 |
Absolute structure | Flack x determined using 1853 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013) | Flack x determined using 1454 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013) |
Absolute structure parameter | 0.0 (3) | 0.00 (3) |
Computer programs: CrystalClear-SM Expert (Rigaku, 2014), SIR92 (Altomare et al., 1994), SHELXL2014 (Sheldrick, 2015), CrystalStructure (Rigaku, 2015).