The crystal structure of the compound, 17S,20S-dihydrofusidic acid diethylene glycol hydrate, C31H50O6·C4H10O3·H2O, consists of 17S,20S-dihydrofusidic acid, diethylene glycol and water. The fusidic acid moiety contains three six-membered rings and one five-membered ring. The fused-ring system adopts a chair, a twist boat, a chair and an envelope conformation. The crystal packing is influenced by hydrogen bonds.
Supporting information
CCDC reference: 172203
Key indicators
- Single-crystal X-ray study
- T = 120 K
- Mean (C-C) = 0.005 Å
- R factor = 0.069
- wR factor = 0.175
- Data-to-parameter ratio = 12.5
checkCIF results
No syntax errors found
ADDSYM reports no extra symmetry
Alert Level B:
RINTA_01 Alert B The value of Rint is greater than 0.15
Rint given 0.182
Alert Level C:
REFLT_03
From the CIF: _diffrn_reflns_theta_max 29.66
From the CIF: _reflns_number_total 5146
TEST2: Reflns within _diffrn_reflns_theta_max
Count of symmetry unique reflns 5491
Completeness (_total/calc) 93.72%
Alert C: < 95% complete
PLAT_213 Alert C Atom C21 has ADP max/min Ratio ........... 3.20
General Notes
REFLT_03
From the CIF: _diffrn_reflns_theta_max 29.66
From the CIF: _reflns_number_total 5146
Count of symmetry unique reflns 5491
Completeness (_total/calc) 93.72%
TEST3: Check Friedels for noncentro structure
Estimate of Friedel pairs measured 0
Fraction of Friedel pairs measured 0.000
Are heavy atom types Z>Si present no
Please check that the estimate of the number of Friedel pairs is
correct. If it is not, please give the correct count in the
_publ_section_exptl_refinement section of the submitted CIF.
0 Alert Level A = Potentially serious problem
1 Alert Level B = Potential problem
2 Alert Level C = Please check
See above for synthesis details.
The absolute configuration of the structure could not be determined due to the
lack of heavy atoms. Therefore, the Friedel pairs were merged. The high values
of Rint and R are related to the rather poor quality of the
crystals. The H atoms were placed in calculated positions (C—H = 0.99 and
1.00 Å and O—H = 0.84 Å).
Data collection: SMART (Siemens, 1995); cell refinement: SAINT (Siemens, 1995); data reduction: SAINT; program(s) used to solve structure: SHELXTL/PC (Sheldrick, 1994); program(s) used to refine structure: SHELXTL/PC; molecular graphics: SHELXTL/PC; software used to prepare material for publication: SHELXTL/PC.
17S,20S-Dihydrofusidic acid diethylene glycol hydrate
top
Crystal data top
C31H50O6·C4H10O3·H2O | Dx = 1.217 Mg m−3 Dm = no Mg m−3 Dm measured by not measured |
Mr = 642.85 | Melting point: no K |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
a = 12.6246 (3) Å | Cell parameters from no reflections |
b = 13.0962 (3) Å | θ = 1.8–29.7° |
c = 21.2134 (5) Å | µ = 0.09 mm−1 |
V = 3507.30 (14) Å3 | T = 120 K |
Z = 4 | Block, colourless |
F(000) = 1408 | 0.33 × 0.33 × 0.26 mm |
Data collection top
Siemens SMART CCD Platform diffractometer | Rint = 0.182 |
Radiation source: rmal-focus sealed tube | θmax = 29.7°, θmin = 1.8° |
ω scans | h = −17→17 |
24333 measured reflections | k = −17→10 |
5146 independent reflections | l = −28→28 |
4433 reflections with I > 2σ(I) | |
Refinement top
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.069 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.175 | H-atom parameters constrained |
S = 1.15 | w = 1/[σ2(Fo2) + (0.0767P)2 + 2.9938P] where P = (Fo2 + 2Fc2)/3 |
5146 reflections | (Δ/σ)max = 0.003 |
412 parameters | Δρmax = 0.53 e Å−3 |
0 restraints | Δρmin = −0.52 e Å−3 |
Crystal data top
C31H50O6·C4H10O3·H2O | V = 3507.30 (14) Å3 |
Mr = 642.85 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 12.6246 (3) Å | µ = 0.09 mm−1 |
b = 13.0962 (3) Å | T = 120 K |
c = 21.2134 (5) Å | 0.33 × 0.33 × 0.26 mm |
Data collection top
Siemens SMART CCD Platform diffractometer | 4433 reflections with I > 2σ(I) |
24333 measured reflections | Rint = 0.182 |
5146 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.069 | 0 restraints |
wR(F2) = 0.175 | H-atom parameters constrained |
S = 1.15 | Δρmax = 0.53 e Å−3 |
5146 reflections | Δρmin = −0.52 e Å−3 |
412 parameters | |
Special details top
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes)
are estimated using the full covariance matrix. The cell e.s.d.'s are taken
into account individually in the estimation of e.s.d.'s in distances, angles
and torsion angles; correlations between e.s.d.'s in cell parameters are only
used when they are defined by crystal symmetry. An approximate (isotropic)
treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s.
planes. |
Refinement. Refinement on F2 for ALL reflections except for 4 with very negative
F2 or flagged by the user for potential systematic errors. Weighted
R-factors wR and all goodnesses of fit S are based on
F2, conventional R-factors R are based on F,
with F set to zero for negative F2. The observed criterion of
F2 > σ(F2) is used only for calculating R-factors
etc. and is t relevant to the choice of reflections for refinement.
R-factors based on F2 are statistically about twice as large
as those based on F, and R- factors based on ALL data will be
even larger. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
C1 | −0.1826 (3) | 0.8289 (2) | −0.2993 (2) | 0.0171 (7) | |
H10 | −0.1625 (3) | 0.7569 (2) | −0.2917 (2) | 0.021* | |
H12 | −0.2481 (3) | 0.8428 (2) | −0.2751 (2) | 0.021* | |
C2 | −0.2058 (3) | 0.8433 (3) | −0.3701 (2) | 0.0202 (7) | |
H21 | −0.1431 (3) | 0.8220 (3) | −0.3949 (2) | 0.024* | |
H22 | −0.2660 (3) | 0.7991 (3) | −0.3824 (2) | 0.024* | |
C3 | −0.2323 (3) | 0.9537 (3) | −0.3851 (2) | 0.0195 (7) | |
H3 | −0.2437 (3) | 0.9606 (3) | −0.4316 (2) | 0.023* | |
O1 | −0.3298 (2) | 0.9757 (2) | −0.35296 (13) | 0.0204 (5) | |
H1 | −0.3474 | 1.0365 | −0.3600 | 0.024* | |
C4 | −0.1419 (3) | 1.0246 (3) | −0.3651 (2) | 0.0181 (7) | |
H4 | −0.0770 (3) | 1.0047 (3) | −0.3891 (2) | 0.022* | |
C5 | −0.1180 (3) | 1.0120 (2) | −0.2939 (2) | 0.0159 (6) | |
H5 | −0.1844 (3) | 1.0314 (2) | −0.2711 (2) | 0.019* | |
C6 | −0.0310 (3) | 1.0848 (3) | −0.2698 (2) | 0.0199 (7) | |
H61 | −0.0618 (3) | 1.1539 (3) | −0.2652 (2) | 0.024* | |
H62 | 0.0255 (3) | 1.0888 (3) | −0.3020 (2) | 0.024* | |
C7 | 0.0198 (3) | 1.0533 (3) | −0.2059 (2) | 0.0182 (7) | |
H71 | 0.0833 (3) | 1.0111 (3) | −0.2142 (2) | 0.022* | |
H72 | 0.0428 (3) | 1.1155 (3) | −0.1832 (2) | 0.022* | |
C8 | −0.0573 (3) | 0.9928 (2) | −0.1639 (2) | 0.0145 (6) | |
C9 | −0.0795 (3) | 0.8903 (2) | −0.2003 (2) | 0.0127 (6) | |
H9 | −0.0105 (3) | 0.8534 (2) | −0.1963 (2) | 0.015* | |
C10 | −0.0936 (3) | 0.8990 (2) | −0.2749 (2) | 0.0153 (6) | |
C11 | −0.1559 (3) | 0.8195 (2) | −0.1653 (2) | 0.0145 (6) | |
H11 | −0.1640 (3) | 0.7553 (2) | −0.1904 (2) | 0.017* | |
O2 | −0.2589 (2) | 0.8644 (2) | −0.15731 (12) | 0.0179 (5) | |
H2 | −0.2985 | 0.8234 | −0.1380 | 0.022* | |
C12 | −0.1107 (3) | 0.7915 (2) | −0.1003 (2) | 0.0141 (6) | |
H121 | −0.1630 (3) | 0.7503 (2) | −0.0766 (2) | 0.017* | |
H122 | −0.0457 (3) | 0.7501 (2) | −0.1056 (2) | 0.017* | |
C13 | −0.0849 (3) | 0.8888 (2) | −0.0638 (2) | 0.0143 (6) | |
H13 | −0.1534 (3) | 0.9272 (2) | −0.0638 (2) | 0.017* | |
C14 | −0.0074 (3) | 0.9621 (2) | −0.0980 (2) | 0.0155 (6) | |
C15 | −0.0006 (3) | 1.0475 (2) | −0.0484 (2) | 0.0201 (7) | |
H151 | −0.0628 (3) | 1.0932 (2) | −0.0515 (2) | 0.024* | |
H152 | 0.0644 (3) | 1.0886 (2) | −0.0546 (2) | 0.024* | |
C16 | 0.0019 (3) | 0.9933 (2) | 0.0164 (2) | 0.0171 (7) | |
H16 | −0.0382 (3) | 1.0345 (2) | 0.0482 (2) | 0.020* | |
O3 | 0.1096 (2) | 0.9774 (2) | 0.03791 (13) | 0.0198 (5) | |
C17 | −0.0531 (3) | 0.8859 (2) | 0.0072 (2) | 0.0140 (6) | |
H17 | −0.1211 (3) | 0.8894 (2) | 0.0313 (2) | 0.017* | |
C28 | −0.1687 (3) | 1.1358 (3) | −0.3818 (2) | 0.0239 (8) | |
H281 | −0.1084 (3) | 1.1798 (3) | −0.3714 (2) | 0.029* | |
H282 | −0.2309 (3) | 1.1577 (3) | −0.3578 (2) | 0.029* | |
H283 | −0.1839 (3) | 1.1408 (3) | −0.4270 (2) | 0.029* | |
C30 | −0.1550 (3) | 1.0622 (2) | −0.1521 (2) | 0.0178 (7) | |
H301 | −0.1931 (3) | 1.0383 (2) | −0.1146 (2) | 0.021* | |
H302 | −0.2022 (3) | 1.0596 (2) | −0.1887 (2) | 0.021* | |
H303 | −0.1314 (3) | 1.1327 (2) | −0.1454 (2) | 0.021* | |
C19 | 0.0120 (3) | 0.8648 (3) | −0.3060 (2) | 0.0197 (7) | |
H191 | 0.0698 (3) | 0.9084 (3) | −0.2910 (2) | 0.024* | |
H192 | 0.0061 (3) | 0.8707 (3) | −0.3519 (2) | 0.024* | |
H193 | 0.0268 (3) | 0.7937 (3) | −0.2947 (2) | 0.024* | |
C18 | 0.1049 (3) | 0.9161 (3) | −0.1050 (2) | 0.0175 (7) | |
H181 | 0.1045 (3) | 0.8646 (3) | −0.1385 (2) | 0.021* | |
H182 | 0.1261 (3) | 0.8841 (3) | −0.0652 (2) | 0.021* | |
H183 | 0.1552 (3) | 0.9703 (3) | −0.1158 (2) | 0.021* | |
C1A | 0.1532 (4) | 1.0492 (3) | 0.0746 (2) | 0.0242 (8) | |
O4 | 0.1087 (3) | 1.1294 (2) | 0.0873 (2) | 0.0385 (8) | |
C2A | 0.2609 (3) | 1.0186 (3) | 0.0967 (2) | 0.0273 (8) | |
H2A1 | 0.3077 (3) | 1.0095 (3) | 0.0603 (2) | 0.033* | |
H2A2 | 0.2561 (3) | 0.9543 (3) | 0.1202 (2) | 0.033* | |
H2A3 | 0.2897 (3) | 1.0720 (3) | 0.1242 (2) | 0.033* | |
C20 | 0.0106 (3) | 0.7963 (2) | 0.0365 (2) | 0.0155 (6) | |
H20 | 0.0808 (3) | 0.7903 (2) | 0.0151 (2) | 0.019* | |
C21 | 0.0270 (3) | 0.8168 (2) | 0.1074 (2) | 0.0176 (7) | |
O5 | 0.1139 (2) | 0.7954 (2) | 0.13239 (13) | 0.0208 (5) | |
O6 | −0.0517 (2) | 0.8505 (2) | 0.13700 (12) | 0.0221 (6) | |
H6 | −0.0354 | 0.8593 | 0.1750 | 0.027* | |
C22 | −0.0498 (3) | 0.6941 (2) | 0.0314 (2) | 0.0213 (8) | |
H221 | −0.1227 (3) | 0.7042 (2) | 0.0474 (2) | 0.026* | |
H222 | −0.0551 (3) | 0.6752 (2) | −0.0136 (2) | 0.026* | |
C23 | 0.0010 (3) | 0.6042 (2) | 0.0676 (2) | 0.0213 (7) | |
H231 | 0.0762 (3) | 0.5972 (2) | 0.0551 (2) | 0.026* | |
H232 | −0.0015 (3) | 0.6181 (2) | 0.1135 (2) | 0.026* | |
C24 | −0.0573 (4) | 0.5064 (3) | 0.0535 (2) | 0.0239 (8) | |
H24 | −0.1324 | 0.5107 | 0.0530 | 0.029* | |
C25 | −0.0158 (4) | 0.4141 (3) | 0.0414 (2) | 0.0249 (8) | |
C26 | −0.0863 (5) | 0.3250 (3) | 0.0250 (2) | 0.0401 (12) | |
H261 | −0.0699 (5) | 0.2673 (3) | 0.0528 (2) | 0.048* | |
H262 | −0.0742 (5) | 0.3050 (3) | −0.0189 (2) | 0.048* | |
H263 | −0.1606 (5) | 0.3447 (3) | 0.0306 (2) | 0.048* | |
C27 | 0.0996 (4) | 0.3915 (3) | 0.0432 (2) | 0.0356 (11) | |
H271 | 0.1195 (4) | 0.3524 (3) | 0.0057 (2) | 0.043* | |
H272 | 0.1160 (4) | 0.3516 (3) | 0.0811 (2) | 0.043* | |
H273 | 0.1395 (4) | 0.4557 (3) | 0.0442 (2) | 0.043* | |
O10 | 0.1041 (2) | 0.5226 (2) | 0.22720 (14) | 0.0215 (5) | |
H101 | 0.120 (4) | 0.527 (4) | 0.269 (2) | 0.026* | |
H102 | 0.145 (4) | 0.551 (4) | 0.200 (3) | 0.026* | |
O7 | 0.0607 (3) | 0.3187 (2) | 0.2373 (2) | 0.0313 (7) | |
C31 | −0.1206 (3) | 0.3673 (3) | 0.2040 (2) | 0.0242 (8) | |
H311 | −0.0894 (3) | 0.4255 (3) | 0.1806 (2) | 0.029* | |
H312 | −0.1826 (3) | 0.3428 (3) | 0.1797 (2) | 0.029* | |
C32 | −0.0388 (3) | 0.2816 (3) | 0.2077 (2) | 0.0235 (8) | |
H321 | −0.0679 (3) | 0.2243 (3) | 0.2327 (2) | 0.028* | |
H322 | −0.0234 (3) | 0.2560 (3) | 0.1647 (2) | 0.028* | |
O8 | −0.1553 (3) | 0.4019 (2) | 0.26314 (15) | 0.0360 (8) | |
H8 | −0.1402 | 0.3609 | 0.2903 | 0.053* | |
C33 | 0.1545 (3) | 0.2500 (3) | 0.2275 (2) | 0.0228 (8) | |
H331 | 0.2196 (3) | 0.2856 (3) | 0.2414 (2) | 0.027* | |
H332 | 0.1618 (3) | 0.2346 (3) | 0.1820 (2) | 0.027* | |
C34 | 0.1429 (4) | 0.1505 (3) | 0.2641 (3) | 0.0361 (11) | |
H341 | 0.1318 (4) | 0.1650 (3) | 0.3094 (3) | 0.043* | |
H342 | 0.0810 (4) | 0.1116 (3) | 0.2483 (3) | 0.043* | |
O9 | 0.2362 (3) | 0.0933 (2) | 0.2556 (2) | 0.0319 (7) | |
H90 | 0.2210 | 0.0348 | 0.2451 | 0.038* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
C1 | 0.023 (2) | 0.0058 (12) | 0.022 (2) | −0.0003 (12) | −0.0022 (14) | −0.0007 (12) |
C2 | 0.028 (2) | 0.0103 (14) | 0.022 (2) | 0.0020 (13) | −0.0001 (15) | −0.0022 (13) |
C3 | 0.028 (2) | 0.0096 (13) | 0.021 (2) | 0.0001 (13) | −0.0017 (15) | 0.0014 (13) |
O1 | 0.0222 (13) | 0.0107 (10) | 0.0282 (13) | 0.0005 (10) | −0.0012 (11) | 0.0052 (10) |
C4 | 0.022 (2) | 0.0100 (13) | 0.022 (2) | 0.0002 (13) | −0.0013 (14) | 0.0045 (13) |
C5 | 0.020 (2) | 0.0075 (12) | 0.020 (2) | −0.0004 (12) | 0.0008 (13) | 0.0010 (12) |
C6 | 0.023 (2) | 0.0087 (13) | 0.028 (2) | −0.0055 (13) | −0.0005 (15) | 0.0039 (13) |
C7 | 0.020 (2) | 0.0107 (13) | 0.024 (2) | −0.0064 (13) | −0.0022 (14) | 0.0033 (13) |
C8 | 0.017 (2) | 0.0052 (12) | 0.021 (2) | −0.0011 (11) | −0.0022 (13) | 0.0013 (12) |
C9 | 0.0150 (14) | 0.0039 (11) | 0.0191 (15) | 0.0005 (11) | −0.0007 (12) | −0.0002 (11) |
C10 | 0.020 (2) | 0.0057 (12) | 0.020 (2) | 0.0008 (12) | 0.0020 (13) | −0.0001 (12) |
C11 | 0.019 (2) | 0.0047 (12) | 0.020 (2) | −0.0030 (12) | 0.0003 (13) | −0.0005 (11) |
O2 | 0.0172 (12) | 0.0085 (9) | 0.0280 (13) | −0.0034 (9) | 0.0012 (10) | 0.0037 (10) |
C12 | 0.018 (2) | 0.0054 (12) | 0.0185 (15) | −0.0022 (11) | −0.0025 (13) | 0.0017 (11) |
C13 | 0.017 (2) | 0.0056 (12) | 0.020 (2) | −0.0006 (11) | −0.0022 (13) | 0.0021 (11) |
C14 | 0.019 (2) | 0.0052 (12) | 0.022 (2) | −0.0005 (12) | −0.0008 (13) | −0.0010 (11) |
C15 | 0.031 (2) | 0.0037 (12) | 0.026 (2) | 0.0000 (13) | −0.005 (2) | 0.0003 (12) |
C16 | 0.021 (2) | 0.0080 (13) | 0.022 (2) | 0.0007 (12) | −0.0031 (14) | −0.0012 (12) |
O3 | 0.0255 (14) | 0.0093 (10) | 0.0248 (12) | −0.0010 (10) | −0.0054 (11) | −0.0027 (10) |
C17 | 0.018 (2) | 0.0042 (12) | 0.0196 (15) | 0.0014 (11) | −0.0015 (13) | −0.0014 (11) |
C28 | 0.030 (2) | 0.0116 (14) | 0.030 (2) | −0.0029 (14) | −0.003 (2) | 0.0065 (14) |
C30 | 0.024 (2) | 0.0052 (12) | 0.024 (2) | 0.0023 (12) | 0.0009 (15) | −0.0007 (12) |
C19 | 0.021 (2) | 0.0127 (14) | 0.025 (2) | 0.0039 (13) | 0.0037 (14) | 0.0016 (14) |
C18 | 0.015 (2) | 0.0119 (13) | 0.025 (2) | −0.0011 (12) | −0.0023 (14) | 0.0014 (13) |
C1A | 0.031 (2) | 0.017 (2) | 0.025 (2) | −0.006 (2) | −0.004 (2) | −0.0010 (14) |
O4 | 0.048 (2) | 0.0171 (13) | 0.050 (2) | 0.0016 (14) | −0.013 (2) | −0.0132 (14) |
C2A | 0.027 (2) | 0.026 (2) | 0.029 (2) | −0.010 (2) | −0.005 (2) | −0.001 (2) |
C20 | 0.021 (2) | 0.0058 (12) | 0.0194 (15) | 0.0033 (12) | −0.0011 (14) | −0.0012 (11) |
C21 | 0.026 (2) | 0.0031 (12) | 0.024 (2) | −0.0019 (12) | −0.0028 (14) | −0.0019 (12) |
O5 | 0.0266 (14) | 0.0097 (10) | 0.0260 (13) | 0.0055 (10) | −0.0055 (12) | −0.0029 (10) |
O6 | 0.0284 (14) | 0.0185 (12) | 0.0195 (11) | 0.0065 (11) | 0.0006 (11) | 0.0027 (10) |
C22 | 0.028 (2) | 0.0075 (13) | 0.028 (2) | 0.0010 (13) | −0.009 (2) | 0.0015 (13) |
C23 | 0.031 (2) | 0.0060 (13) | 0.027 (2) | 0.0002 (14) | −0.004 (2) | 0.0004 (13) |
C24 | 0.035 (2) | 0.0107 (14) | 0.026 (2) | −0.0001 (15) | −0.003 (2) | 0.0013 (13) |
C25 | 0.043 (2) | 0.0105 (15) | 0.022 (2) | −0.004 (2) | −0.003 (2) | 0.0008 (13) |
C26 | 0.066 (4) | 0.012 (2) | 0.042 (3) | −0.010 (2) | −0.008 (2) | 0.004 (2) |
C27 | 0.047 (3) | 0.012 (2) | 0.048 (3) | 0.001 (2) | 0.009 (2) | −0.001 (2) |
O10 | 0.0250 (14) | 0.0124 (10) | 0.0271 (14) | −0.0032 (10) | 0.0027 (12) | 0.0032 (10) |
O7 | 0.038 (2) | 0.0199 (13) | 0.036 (2) | −0.0035 (13) | −0.0006 (14) | −0.0011 (12) |
C31 | 0.031 (2) | 0.0146 (15) | 0.027 (2) | −0.0030 (15) | −0.004 (2) | 0.0026 (14) |
C32 | 0.030 (2) | 0.0129 (15) | 0.028 (2) | −0.0043 (14) | 0.001 (2) | −0.0034 (14) |
O8 | 0.057 (2) | 0.0208 (14) | 0.030 (2) | 0.0200 (15) | 0.006 (2) | 0.0061 (12) |
C33 | 0.028 (2) | 0.0121 (15) | 0.029 (2) | −0.0044 (14) | 0.004 (2) | −0.0034 (14) |
C34 | 0.031 (2) | 0.015 (2) | 0.063 (3) | 0.002 (2) | 0.015 (2) | 0.008 (2) |
O9 | 0.027 (2) | 0.0179 (12) | 0.050 (2) | −0.0013 (12) | −0.0005 (14) | −0.0047 (13) |
Geometric parameters (Å, º) top
C1—C2 | 1.541 (5) | C14—C18 | 1.547 (5) |
C1—C10 | 1.541 (5) | C15—C16 | 1.548 (5) |
C2—C3 | 1.518 (5) | C16—O3 | 1.449 (5) |
C3—O1 | 1.437 (5) | C16—C17 | 1.581 (4) |
C3—C4 | 1.532 (5) | O3—C1A | 1.338 (4) |
C4—C28 | 1.537 (5) | C17—C20 | 1.552 (4) |
C4—C5 | 1.549 (5) | C1A—O4 | 1.221 (5) |
C5—C6 | 1.540 (5) | C1A—C2A | 1.494 (6) |
C5—C10 | 1.564 (4) | C20—C21 | 1.540 (5) |
C6—C7 | 1.555 (5) | C20—C22 | 1.545 (5) |
C7—C8 | 1.539 (5) | C21—O5 | 1.250 (5) |
C8—C30 | 1.553 (5) | C21—O6 | 1.256 (5) |
C8—C9 | 1.574 (4) | C22—C23 | 1.544 (5) |
C8—C14 | 1.585 (5) | C23—C24 | 1.507 (5) |
C9—C11 | 1.530 (4) | C24—C25 | 1.342 (5) |
C9—C10 | 1.598 (5) | C25—C27 | 1.488 (7) |
C10—C19 | 1.554 (5) | C25—C26 | 1.509 (6) |
C11—O2 | 1.437 (4) | O7—C32 | 1.487 (5) |
C11—C12 | 1.535 (5) | O7—C33 | 1.502 (5) |
C12—C13 | 1.528 (4) | C31—O8 | 1.405 (5) |
C13—C14 | 1.551 (5) | C31—C32 | 1.528 (6) |
C13—C17 | 1.558 (5) | C33—C34 | 1.524 (5) |
C14—C15 | 1.538 (5) | C34—O9 | 1.408 (5) |
| | | |
C2—C1—C10 | 113.1 (3) | C15—C14—C18 | 107.3 (3) |
C3—C2—C1 | 111.3 (3) | C15—C14—C13 | 99.5 (3) |
O1—C3—C2 | 106.3 (3) | C18—C14—C13 | 112.5 (3) |
O1—C3—C4 | 112.6 (3) | C15—C14—C8 | 116.1 (3) |
C2—C3—C4 | 110.8 (3) | C18—C14—C8 | 112.2 (3) |
C3—C4—C28 | 110.3 (3) | C13—C14—C8 | 108.6 (3) |
C3—C4—C5 | 110.6 (3) | C14—C15—C16 | 106.0 (3) |
C28—C4—C5 | 111.7 (3) | O3—C16—C15 | 111.3 (3) |
C6—C5—C4 | 113.3 (3) | O3—C16—C17 | 108.9 (3) |
C6—C5—C10 | 111.1 (3) | C15—C16—C17 | 106.8 (3) |
C4—C5—C10 | 112.9 (3) | C1A—O3—C16 | 117.9 (3) |
C5—C6—C7 | 114.7 (3) | C20—C17—C13 | 122.7 (3) |
C8—C7—C6 | 112.4 (3) | C20—C17—C16 | 113.3 (3) |
C7—C8—C30 | 107.1 (3) | C13—C17—C16 | 102.2 (3) |
C7—C8—C9 | 105.5 (3) | O4—C1A—O3 | 122.9 (4) |
C30—C8—C9 | 115.9 (3) | O4—C1A—C2A | 125.4 (4) |
C7—C8—C14 | 113.0 (3) | O3—C1A—C2A | 111.7 (3) |
C30—C8—C14 | 108.8 (3) | C21—C20—C22 | 106.6 (3) |
C9—C8—C14 | 106.7 (2) | C21—C20—C17 | 109.3 (3) |
C11—C9—C8 | 113.1 (3) | C22—C20—C17 | 111.8 (3) |
C11—C9—C10 | 117.0 (3) | O5—C21—O6 | 124.1 (3) |
C8—C9—C10 | 116.4 (2) | O5—C21—C20 | 119.6 (3) |
C1—C10—C19 | 108.2 (3) | O6—C21—C20 | 116.2 (3) |
C1—C10—C5 | 109.5 (3) | C23—C22—C20 | 114.9 (3) |
C19—C10—C5 | 109.5 (3) | C24—C23—C22 | 110.3 (3) |
C1—C10—C9 | 111.8 (3) | C25—C24—C23 | 127.8 (4) |
C19—C10—C9 | 107.7 (3) | C24—C25—C27 | 123.8 (4) |
C5—C10—C9 | 110.1 (3) | C24—C25—C26 | 120.7 (4) |
O2—C11—C9 | 112.3 (3) | C27—C25—C26 | 115.5 (4) |
O2—C11—C12 | 109.2 (3) | C32—O7—C33 | 114.3 (3) |
C9—C11—C12 | 110.2 (3) | O8—C31—C32 | 113.7 (3) |
C13—C12—C11 | 109.6 (2) | O7—C32—C31 | 110.6 (3) |
C12—C13—C14 | 114.4 (3) | O7—C33—C34 | 111.5 (3) |
C12—C13—C17 | 121.6 (3) | O9—C34—C33 | 108.0 (3) |
C14—C13—C17 | 107.8 (3) | | |
| | | |
C10—C1—C2—C3 | −56.0 (4) | C12—C13—C14—C18 | −66.4 (4) |
C1—C2—C3—O1 | −65.0 (4) | C17—C13—C14—C18 | 72.2 (3) |
C1—C2—C3—C4 | 57.6 (4) | C12—C13—C14—C8 | 58.4 (3) |
O1—C3—C4—C28 | −62.3 (4) | C17—C13—C14—C8 | −163.0 (3) |
C2—C3—C4—C28 | 178.8 (3) | C7—C8—C14—C15 | 77.0 (4) |
O1—C3—C4—C5 | 61.7 (4) | C30—C8—C14—C15 | −41.8 (4) |
C2—C3—C4—C5 | −57.2 (4) | C9—C8—C14—C15 | −167.5 (3) |
C3—C4—C5—C6 | −177.4 (3) | C7—C8—C14—C18 | −47.0 (3) |
C28—C4—C5—C6 | −54.2 (4) | C30—C8—C14—C18 | −165.8 (3) |
C3—C4—C5—C10 | 55.1 (4) | C9—C8—C14—C18 | 68.5 (3) |
C28—C4—C5—C10 | 178.3 (3) | C7—C8—C14—C13 | −172.0 (3) |
C4—C5—C6—C7 | −161.9 (3) | C30—C8—C14—C13 | 69.3 (3) |
C10—C5—C6—C7 | −33.5 (4) | C9—C8—C14—C13 | −56.4 (3) |
C5—C6—C7—C8 | −28.7 (4) | C18—C14—C15—C16 | −77.8 (3) |
C6—C7—C8—C30 | −59.1 (4) | C13—C14—C15—C16 | 39.5 (4) |
C6—C7—C8—C9 | 65.0 (4) | C8—C14—C15—C16 | 155.7 (3) |
C6—C7—C8—C14 | −178.9 (3) | C14—C15—C16—O3 | 94.0 (3) |
C7—C8—C9—C11 | −179.8 (3) | C14—C15—C16—C17 | −24.7 (4) |
C30—C8—C9—C11 | −61.5 (4) | C15—C16—O3—C1A | 92.3 (4) |
C14—C8—C9—C11 | 59.8 (4) | C17—C16—O3—C1A | −150.3 (3) |
C7—C8—C9—C10 | −40.1 (4) | C12—C13—C17—C20 | 33.2 (5) |
C30—C8—C9—C10 | 78.2 (4) | C14—C13—C17—C20 | −101.8 (4) |
C14—C8—C9—C10 | −160.5 (3) | C12—C13—C17—C16 | 161.4 (3) |
C2—C1—C10—C19 | −67.3 (4) | C14—C13—C17—C16 | 26.4 (3) |
C2—C1—C10—C5 | 52.0 (4) | O3—C16—C17—C20 | 12.6 (4) |
C2—C1—C10—C9 | 174.3 (3) | C15—C16—C17—C20 | 132.9 (3) |
C6—C5—C10—C1 | 179.6 (3) | O3—C16—C17—C13 | −121.3 (3) |
C4—C5—C10—C1 | −51.9 (4) | C15—C16—C17—C13 | −1.0 (4) |
C6—C5—C10—C19 | −62.0 (4) | C16—O3—C1A—O4 | −4.6 (6) |
C4—C5—C10—C19 | 66.6 (4) | C16—O3—C1A—C2A | 175.8 (3) |
C6—C5—C10—C9 | 56.2 (4) | C13—C17—C20—C21 | −179.2 (3) |
C4—C5—C10—C9 | −175.2 (3) | C16—C17—C20—C21 | 57.5 (4) |
C11—C9—C10—C1 | −2.0 (4) | C13—C17—C20—C22 | −61.4 (4) |
C8—C9—C10—C1 | −140.1 (3) | C16—C17—C20—C22 | 175.3 (3) |
C11—C9—C10—C19 | −120.7 (3) | C22—C20—C21—O5 | 98.7 (4) |
C8—C9—C10—C19 | 101.2 (3) | C17—C20—C21—O5 | −140.3 (3) |
C11—C9—C10—C5 | 120.0 (3) | C22—C20—C21—O6 | −78.1 (4) |
C8—C9—C10—C5 | −18.1 (4) | C17—C20—C21—O6 | 42.9 (4) |
C8—C9—C11—O2 | 62.4 (4) | C21—C20—C22—C23 | −52.5 (4) |
C10—C9—C11—O2 | −77.0 (3) | C17—C20—C22—C23 | −171.9 (3) |
C8—C9—C11—C12 | −59.5 (3) | C20—C22—C23—C24 | −173.7 (3) |
C10—C9—C11—C12 | 161.0 (3) | C22—C23—C24—C25 | 137.0 (4) |
O2—C11—C12—C13 | −69.0 (3) | C23—C24—C25—C27 | 3.2 (7) |
C9—C11—C12—C13 | 54.8 (4) | C23—C24—C25—C26 | −177.0 (4) |
C11—C12—C13—C14 | −56.7 (4) | C33—O7—C32—C31 | −164.3 (3) |
C11—C12—C13—C17 | 171.0 (3) | O8—C31—C32—O7 | −65.0 (4) |
C12—C13—C14—C15 | −179.7 (3) | C32—O7—C33—C34 | −69.6 (4) |
C17—C13—C14—C15 | −41.2 (3) | O7—C33—C34—O9 | −176.4 (4) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1···O6i | 0.84 | 1.954 | 2.732 (4) | 153.7 |
O2—H2···O5ii | 0.84 | 1.913 | 2.690 (3) | 153.4 |
O6—H6···O7iii | 0.84 | 1.961 | 2.701 (4) | 147.0 |
O8—H8···O5iv | 0.81 | 1.880 | 2.670 (4) | 164.6 |
O9—H90···O8iv | 0.82 | 1.936 | 2.736 (4) | 164.6 |
O10—H101···O1v | 0.91 (4) | 1.89 (4) | 2.795 (4) | 172.0 |
O10—H102···O2v | 0.86 (6) | 1.88 (5) | 2.717 (4) | 166.0 |
Symmetry codes: (i) −x−1/2, −y+2, z−1/2; (ii) x−1/2, −y+3/2, −z; (iii) −x, y+1/2, −z+1/2; (iv) −x, y−1/2, −z+1/2; (v) x+1/2, −y+3/2, −z. |
Experimental details
Crystal data |
Chemical formula | C31H50O6·C4H10O3·H2O |
Mr | 642.85 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 120 |
a, b, c (Å) | 12.6246 (3), 13.0962 (3), 21.2134 (5) |
V (Å3) | 3507.30 (14) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.09 |
Crystal size (mm) | 0.33 × 0.33 × 0.26 |
|
Data collection |
Diffractometer | Siemens SMART CCD Platform diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 24333, 5146, 4433 |
Rint | 0.182 |
(sin θ/λ)max (Å−1) | 0.696 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.069, 0.175, 1.15 |
No. of reflections | 5146 |
No. of parameters | 412 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.53, −0.52 |
Selected torsion angles (º) topC15—C16—O3—C1A | 92.3 (4) | C22—C20—C21—O5 | 98.7 (4) |
C17—C16—O3—C1A | −150.3 (3) | C17—C20—C21—O5 | −140.3 (3) |
C16—O3—C1A—O4 | −4.6 (6) | C22—C20—C21—O6 | −78.1 (4) |
C16—O3—C1A—C2A | 175.8 (3) | C17—C20—C21—O6 | 42.9 (4) |
C13—C17—C20—C21 | −179.2 (3) | C17—C20—C22—C23 | −171.9 (3) |
C16—C17—C20—C21 | 57.5 (4) | C20—C22—C23—C24 | −173.7 (3) |
C13—C17—C20—C22 | −61.4 (4) | C22—C23—C24—C25 | 137.0 (4) |
C16—C17—C20—C22 | 175.3 (3) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1···O6i | 0.84 | 1.954 | 2.732 (4) | 153.7 |
O2—H2···O5ii | 0.84 | 1.913 | 2.690 (3) | 153.4 |
O6—H6···O7iii | 0.84 | 1.961 | 2.701 (4) | 147.0 |
O8—H8···O5iv | 0.81 | 1.880 | 2.670 (4) | 164.6 |
O9—H90···O8iv | 0.82 | 1.936 | 2.736 (4) | 164.6 |
O10—H101···O1v | 0.91 (4) | 1.89 (4) | 2.795 (4) | 172.0 |
O10—H102···O2v | 0.86 (6) | 1.88 (5) | 2.717 (4) | 166.0 |
Symmetry codes: (i) −x−1/2, −y+2, z−1/2; (ii) x−1/2, −y+3/2, −z; (iii) −x, y+1/2, −z+1/2; (iv) −x, y−1/2, −z+1/2; (v) x+1/2, −y+3/2, −z. |
Fusidic acid belongs to a family of naturally occurring antibiotics known as fusidanes having in common a tetracyclic ring system with the unique chair–boat–chair conformation, a carboxylic acid bearing side chain linked to the ring system at C17 via a double bond and an acetate group at C16. The fusidanes show high degree of antibacterial activity and have a similar spectrum. Fusidic acid, the most potent of the fusidanes, was first isolated from Fusidium coccineum in 1960 (Godtfredsen et al., 1962) and has since 1962 been used clinically in treatment of both topical and systemic infections caused by staphylococci. The clinical importance of fusidic acid is furthermore due to its excellent distribution in various tissues, low degree of toxicity and allergic reactions and the absence of cross-resistance with other clinically used antibiotics (Christiansen, 1999; Turnidge & Collign, 1999; Collign & Turnidge, 1999; Spelman, 1999). The structure–activity relationship (SAR) of fusidic acid has earlier undergone extensive studies (von Daehne et al., 1979) and a large number of related analogues have been prepared. However, only a very few of these analogues showed activities comparable with that of fusidic acid and most of them had a similar antibacterial spectrum and were cross-resistant. In spite of extensive functional and structural modifications of the fusidic acid molecule, studies of including side-chain modifications are limited (Godtfredsen et al., 1965; von Daehne et al., 1979). As part of our renewed interest in improving the antibiotic properties of fusidic acid, we decided to focus on the relatively unexplored side chain. Two saturated fusidic acid analogues were synthesized several years ago (Godtfredsen et al., 1966). They have in common the 17R configuration but are epimers at C20 and were both found to be virtually inactive. The corresponding analogues with the opposite 17S configuration have not been available until now due to the lack of appropriate synthetic methodology. We recently developed such a methodology for the preparation of 17S,20R– and 17S,20S-dihydrofusidic acid (Duvold et al., 2001). Antibacterial testing has revealed potent antibacterial activities of one of these epimers, the 17S,20S-dihydrofusidic acid.
The molecule of 17S,20S-dihydrofusidic acid is composed of four fused rings of which three are six-membered rings, A (C1—C5,C10), B (C5—C10) and C (C8—C9,C11—C14) and one is five-membered, D (C13—C17). The rings A, B and C adopt chair, twist boat, chair conformations respectively and D is in an envelope form with apex at C14. The same conformations of the tetracyclic ring system were found in fusidic acid methyl ester 3-p-bromobenzen (Cooper & Hodgkin, 1968). Bond lengths and angles of the present structure are in the expected ranges. The molecular geometry and the numbering are displayed in Fig. 1. The acetate group at C16 is twisted from the plane E (C13/C15—C17) with torsion angles of 92.3 (4) (C15—C16—O3—C1A) and -150.3 (3)° (C17—C16—O3—C1A). Also, the carboxylic acid group is twisted from plane E the torsion angles being -179.2 (3) (C13—C17—C20—C21) and 57.5 (4)° (C16—C17—C20—C21). The major side chain attached at C17 is elongated as is the case with saturated side chains. It does not curl back on itself as found in fusidic acid methyl ester 3-p-bromobenzen (Cooper & Hodgkin, 1968), where the C17–C20 bond is a double bond. The crystal packing is influenced by hydrogen bonds (Table 2). The O1 and O2 hydroxyl groups form hydrogen bonds with the carboxylic acid group.
There are also hydrogen bonds between the water molecule and the O1 and O2 hydoxyl groups. The carbolic acid group is involved in hydrogen bonds with the diethylene ether. Finally, the symetry related diethylene glycol molecules are linked by hydrogen-bond interactions through O8 and O9.