(1R,3S,6S)-6-tert-Butyl-1-hydroxy­methyl-5-methoxy-6-methyl-7-oxa-4-aza­spiro­[2.5]­oct-4-en-8-one and di­methyl [(1S,1′R,3′S,6′S)-(6′-tert-butyl-5′-methoxy-6′-methyl-8′-oxo-7′-oxa-4′-aza­spiro­[2.5]­oct-4′-en-1′-yl)­hydroxy­methyl]­phospho­nate

The mol­ecules of the title compounds, C₁₃H₂₁NO₄, (I), and C₁₅H₂₆NO₇P, (II), are linked into chains along the c direction in (I) and along the b axis in (II) through O—H...O hydrogen bonds. The heteroatomic ring in (I) adopts a twist-boat conformation, while that in (II) has a conformation intermediate between boat and twist-boat. The P atom has a distorted tetrahedral geometry.

S1. Comment

Aminophosphonic acids are the analogues of natural amino acids in which the carboxylic acid group is replaced by the phosphonic group. Aminophosphonic acids and their esters and salts have attracted attention because of their broad applications, viz. in analytical chemistry (ligands for transitions metal cations), in agriculture (herbicides, pesticides and growth regulator in plants) and in medicine (antibiotics, antivirals and enzyme inhibitors) (Kalir et al., 1996; Hudson & Pianka, 1996; Kukhar & Hudson, 1999). In recent years, unnatural λ-amino acids have played an important role in the field of peptide chemistry. In this context, excitatory amino acids (EAAs) are of special interest because of their neurotransmission propetries in the central nervous system. The discovery that phosphono-substituted analogues of λ-amino acids increased potency and selectivity led to a major advance in the design of the N-methyl-_D-aspartate (NMDA) receptor antagonists (Davies et al., 1981; Evans et al., 1982).

The importance of EAAs, in particular L-glutamic acid, (1), is becoming increasingly apparent. Specific and selective EAA agonists and antagonists have been developed (Hansen & Krogsgaard, 1990; Jonhson & Korner, 1988) There were postulated to be five defined EAA receptor subtypes (Monaghan et al., 1989). One of these, the L-amino-4-phosphonobutanoic acid [L—AP4; (2)] EAA receptor subtype, is delineated by a unique responsiveness to L—AP4 (Scheme 1). Compounds with the structure of (3) mimic L—AP4 more closely than do the cyclopentyl analogues (Kroona et al., 1991).

In this paper, we present the crystal structure of two compounds as the precursor to the synthesis of the cyclic analog of L—AP4, employing a chiral 6-tert-butyl-5-methoxy-6-methyl-3,6- dihydro-2H-1,4-oxazin-2-one (4).

A single-crystal X-ray diffraction study of these compounds was undertaken for a final examination of the absolute structure, establishing the configuration of the chiral atoms. The determination of the crystal structure revealed the reaction sequence, in which the attack of the deprotonated form of the oxazinone ring commenced with the terminal C atom in epichlorohydrin (Koch et al., 2003). Moreover, the structure of (II) was solved in order to elucidate the geometry around the P atom.

The substituents at C6 and C3 are in a cis conformation with respect to the heterocyclic ring, which confirms the proposed mechanism of the chemical process (Koch et al., 2003).

The heteroatomic ring in (I) has a twist-boat conformation, while in (II) the ring adopts a conformation between boat and twist-boat. The puckering parameters (Cremer & Pople, 1975) are as follows: Q_T= 0.232 (3) Å, ϕ₂= −144.6 (8)° and θ₂= 104.5 (8)° in (I), and Q_T= 0.194 (3) Å, ϕ₂= −133.3 (8)° and θ₂= 101.5 (8)° in (II), corresponding to the O1—C6—C5—N4—C3—C2 atom sequence, with a twofold pseudo-axis passing through the midpoint of the O1—C6 bond and atom C2 [asymmetry parameters Δ₂= 0.01 (1) and Δ₂= 0.03 (1) for (I)]. Four low values of the asymmetry parameters for (II) confirm that the conformation of the ring is between boat and twist-boat. A pseudo-twofold axis passes through the midpoint of the O1—C6 bond and atom C2 [Δ₂= 0.03 (1) and Δ₂= 0.03 (1)] and a mirror plane through the midpoint of the N4—C5 bond and atom C3 [Δ_s= 0.03 (1) and Δ_s= 0.03 (1); atom sequence as mentioned above].

An intermolecular O—H···O hydrogen bond exists in both structures. In (I), an O90—H90···O21ⁱ hydrogen bond is formed, but in (II), atom O21 does not act as an acceptor for hydrogen bonds. Here, the presence of the phosphonate group has the effect of changing the acceptor atom (O30 instead of O21), and thus an O90—H91—O30ⁱⁱ hydrogen bond is observed. These interactions create the chain graph-set motifs C(7) and C(5) in (I) and (II) (Bernstein et al., 1995), running along the c and b axis, respectively.

The P atom displays a distorted tetrahedral coordination geometry, with the largest deviations from the ideal values being for the O20—P1—C9 and O30—P1—C9 angles (the smallest and largest angles).

Bond distances and angles are in a good agreement with the expected values (Allen et al., 1987).

S2. Experimental

Compound (I) was prepared? from (S)-6-tert-5-methoxy-6-methyl-3,6-dihydro-2H- 1,4-oxazin-2-one (65 mg, 0.33 mmol) in THF (3.5 ml), NaN(SiCH₃)₂ (685µl, 0.685 mmol, 2.1 equiv.) and (R)-(-)-epichlorohydrin (92 mg, 78 µl, 0.99 mmol, 3.0 mmol), with a reaction time of 24 h. CC (petrol ether/acetate, 70:30) yielded (I) as colorless crystals (40 mg, 47%, from diisopropyl ether by slow evaporation; m.p. 434.5–436 K). [α]_D²⁰= − 4.0 (c=0.55, CHCl₃).

For the preparation of (II), to (1R,3S,6S)-6-tert-butyl-5-methoxy-6-methyl −4-aza-7-oxaspiro[2.5]oct-4-en-8-one-1-carbaldehyde) (64.0 mg, 0.253 mmol) in THF (3.0 ml) were added HP(O)(OMe)₂ (20.88 µl, 0.228 mmol, 0.9 equiv.) and triethylamine (2.55 mg, 0.0253 mmol, 3.5 µl). The reaction mixture was stirred for 1 h at room temperature. The crude product was filtered off, dried and crystallized from diisopropyl ether (yield 86.6 mg, 97%; m.p. 434–436 K) by slow evaporation. [α]_D²⁰= + 19.2 (c=0.25, CHCl₃).

S3. Refinement

All H atoms were positioned geometrically and refined as riding, with O—H distaces of 0.82 Å and C—H distances in the range 0.96–0.98 Å. U_iso values were constrained to be 1.5U_eq for H atoms from methyl groups and 1.2U_eq for other H atoms. The absolute configuration has been assigned on the basis of the known configuration of the reagents for both compounds. The Flack (1983) parameter for (I) could not be defined because the number of Friedel pairs was insufficient. In the case of (II), the Flack parameter is in agreement with the expected configuration.

Computing details

For both compounds, data collection: MSC/AFC Diffractometer Control Software (Molecular Structure Corporation, 1989a); cell refinement: MSC/AFC Diffractometer Control Software; data reduction: TEXSAN (Molecular Structure Corporation, 1989b); program(s) used to solve structure: SHELXS86 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: PARST97 (Nardelli, 1996).

Figures

Scheme 1. Ligands for NMDA receptor. Fig. 1. A view of (I), with the atom-labelling scheme. Displacement ellipsoids are shown at the 50% probability level Fig. 2. A view of (II), with the atom-labelling scheme. Displacement ellipsoids are shown at the 50% probability level Fig. 3. The chain along the c axis of molecules of (I) linked by hydrogen bonds in the unit cell. Fig. 4. The chain along the b axis of molecules of (II) linked by hydrogen bonds in the unit cell.

(I) (1R,3S,6S)-[6-tert-butyl-1-hydroxymethyl-5-methyoxy-6-methyl-7-oxa-8-oxo-4-aza-spiro[2.5]oct-4-en-8-one

Crystal data

C13H21NO4	Dx = 1.181 Mg m^−3
Mr = 255.31	Melting point: C13 H21 N O4 K
Orthorhombic, P212121	Cu Kα radiation, λ = 1.54178 Å
a = 8.134 (3) Å	Cell parameters from 25 reflections
b = 22.802 (2) Å	θ = 23.5–29.4°
c = 7.744 (2) Å	µ = 0.72 mm^−1
V = 1436.3 (7) Å^3	T = 293 K
Z = 4	Plate, colorless
F(000) = 552	0.5 × 0.2 × 0.1 mm

Data collection

AFC5S Rigaku diffractometer	1195 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.000
Graphite monochromator	θmax = 67.5°, θmin = 3.9°
ω scan	h = −9→9
Absorption correction: analytical (De Meulenaer & Tompa, 1965)	k = −21→27
Tmin = 0.82, Tmax = 0.92	l = −4→9
1480 measured reflections	3 standard reflections every 150 reflections
1480 independent reflections	intensity decay: <2%

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.052	w = 1/[σ^2(Fo^2) + (0.1207P)^2] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.163	(Δ/σ)max < 0.001
S = 1.02	Δρmax = 0.40 e Å^−3
1480 reflections	Δρmin = −0.16 e Å^−3
170 parameters	Extinction correction: SHELXL97, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.017 (2)
Primary atom site location: structure-invariant direct methods

Special details

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 of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based

on F, with F set to zero for negative F². The threshold expression of

F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not 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 (Ų)

	x	y	z	Uiso*/Ueq
O1	0.8882 (3)	0.61951 (11)	0.9203 (3)	0.0650 (7)
C2	1.0281 (4)	0.60630 (17)	0.8383 (4)	0.0611 (8)
O21	1.1576 (3)	0.61483 (15)	0.9133 (3)	0.0822 (9)
C3	1.0161 (4)	0.58000 (14)	0.6645 (4)	0.0560 (8)
N4	0.8584 (3)	0.56568 (12)	0.5973 (4)	0.0579 (7)
C5	0.7336 (4)	0.58646 (13)	0.6730 (5)	0.0562 (8)
O50	0.5803 (3)	0.57494 (12)	0.6146 (4)	0.0729 (8)
C50	0.5710 (6)	0.5411 (2)	0.4581 (7)	0.0978 (16)
H50A	0.4583	0.5378	0.4227	0.147*
H50B	0.6154	0.5027	0.4781	0.147*
H50C	0.6332	0.5603	0.3691	0.147*
C6	0.7279 (4)	0.62403 (14)	0.8336 (4)	0.0566 (8)
C61	0.6079 (5)	0.59904 (19)	0.9619 (5)	0.0768 (11)
H61A	0.4978	0.6048	0.9207	0.115*
H61B	0.6210	0.6185	1.0710	0.115*
H61C	0.6283	0.5578	0.9761	0.115*
C62	0.7006 (5)	0.69059 (13)	0.7918 (5)	0.0693 (10)
C65	0.5314 (6)	0.70043 (17)	0.7102 (7)	0.0913 (14)
H65A	0.5312	0.6852	0.5946	0.137*
H65B	0.5076	0.7417	0.7076	0.137*
H65C	0.4492	0.6806	0.7773	0.137*
C63	0.7082 (7)	0.7260 (2)	0.9596 (7)	0.0999 (15)
H63A	0.7013	0.7671	0.9335	0.150*
H63B	0.8100	0.7181	1.0178	0.150*
H63C	0.6179	0.7151	1.0328	0.150*
C64	0.8325 (7)	0.71294 (18)	0.6685 (8)	0.0990 (16)
H64A	0.9386	0.7092	0.7219	0.149*
H64B	0.8120	0.7534	0.6419	0.149*
H64C	0.8302	0.6903	0.5641	0.149*
C7	1.1581 (5)	0.53997 (17)	0.6155 (5)	0.0675 (9)
H7A	1.2435	0.5336	0.7009	0.081*
H7B	1.1338	0.5063	0.5434	0.081*
C8	1.1472 (4)	0.59819 (18)	0.5363 (4)	0.0636 (9)
H8	1.2266	0.6268	0.5805	0.076*
C9	1.1008 (5)	0.6063 (3)	0.3483 (5)	0.0844 (13)
H9A	1.0419	0.5722	0.3063	0.101*
H9B	1.0308	0.6404	0.3349	0.101*
O90	1.2456 (4)	0.6137 (3)	0.2571 (4)	0.1191 (13)
H90	1.2255	0.6147	0.1534	0.179*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0625 (14)	0.0829 (15)	0.0497 (11)	−0.0006 (12)	−0.0023 (11)	−0.0036 (12)
C2	0.0570 (18)	0.080 (2)	0.0459 (15)	−0.0039 (17)	0.0018 (16)	0.0067 (17)
O21	0.0645 (16)	0.127 (2)	0.0548 (13)	−0.0073 (16)	−0.0135 (14)	−0.0034 (16)
C3	0.0510 (17)	0.0649 (18)	0.0522 (16)	0.0000 (14)	−0.0056 (16)	−0.0032 (15)
N4	0.0519 (15)	0.0601 (14)	0.0618 (16)	−0.0018 (12)	−0.0017 (14)	−0.0086 (13)
C5	0.0507 (17)	0.0564 (15)	0.0616 (18)	−0.0041 (14)	−0.0035 (16)	−0.0056 (16)
O50	0.0527 (14)	0.0784 (15)	0.088 (2)	−0.0015 (11)	−0.0058 (14)	−0.0300 (14)
C50	0.069 (3)	0.116 (3)	0.109 (3)	0.000 (2)	−0.012 (3)	−0.060 (3)
C6	0.0550 (17)	0.0615 (16)	0.0532 (16)	−0.0003 (14)	−0.0018 (16)	−0.0031 (15)
C61	0.071 (2)	0.084 (2)	0.075 (2)	−0.006 (2)	0.020 (2)	−0.001 (2)
C62	0.076 (2)	0.0545 (17)	0.077 (2)	0.0009 (16)	−0.001 (2)	−0.0087 (18)
C65	0.101 (3)	0.067 (2)	0.107 (3)	0.015 (2)	−0.020 (3)	−0.008 (2)
C63	0.107 (3)	0.086 (3)	0.107 (4)	0.004 (3)	−0.004 (3)	−0.040 (3)
C64	0.114 (4)	0.061 (2)	0.122 (4)	−0.002 (2)	0.026 (4)	0.017 (3)
C7	0.0554 (18)	0.079 (2)	0.068 (2)	0.0078 (16)	0.0004 (19)	0.0019 (19)
C8	0.0579 (19)	0.084 (2)	0.0493 (16)	−0.0108 (18)	0.0038 (17)	0.0032 (17)
C9	0.065 (2)	0.140 (4)	0.0489 (17)	−0.007 (3)	0.0116 (18)	−0.003 (2)
O90	0.094 (2)	0.201 (3)	0.0621 (16)	−0.007 (3)	0.0051 (17)	0.012 (2)

Geometric parameters (Å, º)

O1—C2	1.338 (4)	C62—C63	1.531 (6)
O1—C6	1.470 (4)	C62—C65	1.531 (7)
C2—O21	1.218 (4)	C65—H65A	0.9600
C2—C3	1.477 (5)	C65—H65B	0.9600
C3—N4	1.422 (4)	C65—H65C	0.9600
C3—C8	1.514 (5)	C63—H63A	0.9600
C3—C7	1.520 (5)	C63—H63B	0.9600
N4—C5	1.264 (4)	C63—H63C	0.9600
C5—O50	1.352 (4)	C64—H64A	0.9600
C5—C6	1.510 (5)	C64—H64B	0.9600
O50—C50	1.438 (5)	C64—H64C	0.9600
C50—H50A	0.9600	C7—C8	1.465 (5)
C50—H50B	0.9600	C7—H7A	0.9700
C50—H50C	0.9600	C7—H7B	0.9700
C6—C61	1.505 (5)	C8—C9	1.516 (5)
C6—C62	1.567 (4)	C8—H8	0.9800
C61—H61A	0.9600	C9—O90	1.384 (5)
C61—H61B	0.9600	C9—H9A	0.9700
C61—H61C	0.9600	C9—H9B	0.9700
C62—C64	1.524 (7)	O90—H90	0.8200
C2—O1—C6	123.6 (2)	C65—C62—C6	110.7 (3)
O21—C2—O1	118.2 (3)	C62—C65—H65A	109.5
O21—C2—C3	123.8 (3)	C62—C65—H65B	109.5
O1—C2—C3	117.9 (3)	H65A—C65—H65B	109.5
N4—C3—C2	119.1 (3)	C62—C65—H65C	109.5
N4—C3—C8	117.3 (3)	H65A—C65—H65C	109.5
C2—C3—C8	116.1 (3)	H65B—C65—H65C	109.5
N4—C3—C7	117.1 (3)	C62—C63—H63A	109.5
C2—C3—C7	114.9 (3)	C62—C63—H63B	109.5
C8—C3—C7	57.7 (2)	H63A—C63—H63B	109.5
C5—N4—C3	117.9 (3)	C62—C63—H63C	109.5
N4—C5—O50	120.8 (3)	H63A—C63—H63C	109.5
N4—C5—C6	128.2 (3)	H63B—C63—H63C	109.5
O50—C5—C6	110.9 (3)	C62—C64—H64A	109.5
C5—O50—C50	115.8 (3)	C62—C64—H64B	109.5
O50—C50—H50A	109.5	H64A—C64—H64B	109.5
O50—C50—H50B	109.5	C62—C64—H64C	109.5
H50A—C50—H50B	109.5	H64A—C64—H64C	109.5
O50—C50—H50C	109.5	H64B—C64—H64C	109.5
H50A—C50—H50C	109.5	C8—C7—C3	60.9 (2)
H50B—C50—H50C	109.5	C8—C7—H7A	117.7
O1—C6—C61	104.3 (3)	C3—C7—H7A	117.7
O1—C6—C5	108.0 (3)	C8—C7—H7B	117.7
C61—C6—C5	110.4 (3)	C3—C7—H7B	117.7
O1—C6—C62	106.7 (3)	H7A—C7—H7B	114.8
C61—C6—C62	114.3 (3)	C7—C8—C3	61.3 (2)
C5—C6—C62	112.6 (3)	C7—C8—C9	121.8 (4)
C6—C61—H61A	109.5	C3—C8—C9	119.2 (3)
C6—C61—H61B	109.5	C7—C8—H8	114.7
H61A—C61—H61B	109.5	C3—C8—H8	114.7
C6—C61—H61C	109.5	C9—C8—H8	114.7
H61A—C61—H61C	109.5	O90—C9—C8	107.0 (3)
H61B—C61—H61C	109.5	O90—C9—H9A	110.3
C64—C62—C63	109.1 (4)	C8—C9—H9A	110.3
C64—C62—C65	109.0 (4)	O90—C9—H9B	110.3
C63—C62—C65	108.0 (4)	C8—C9—H9B	110.3
C64—C62—C6	110.7 (3)	H9A—C9—H9B	108.6
C63—C62—C6	109.3 (4)	C9—O90—H90	109.5
C6—O1—C2—O21	165.8 (3)	N4—C5—C6—C62	101.4 (4)
C6—O1—C2—C3	−16.6 (5)	O50—C5—C6—C62	−80.1 (4)
O21—C2—C3—N4	172.7 (3)	O1—C6—C62—C64	62.3 (4)
O1—C2—C3—N4	−4.8 (5)	C61—C6—C62—C64	177.0 (4)
O21—C2—C3—C8	−38.5 (5)	C5—C6—C62—C64	−56.0 (5)
O1—C2—C3—C8	144.1 (3)	O1—C6—C62—C63	−57.9 (4)
O21—C2—C3—C7	26.2 (5)	C61—C6—C62—C63	56.9 (5)
O1—C2—C3—C7	−151.3 (3)	C5—C6—C62—C63	−176.1 (4)
C2—C3—N4—C5	13.9 (4)	O1—C6—C62—C65	−176.7 (3)
C8—C3—N4—C5	−134.6 (3)	C61—C6—C62—C65	−62.0 (4)
C7—C3—N4—C5	159.6 (3)	C5—C6—C62—C65	65.0 (4)
C3—N4—C5—O50	179.4 (3)	N4—C3—C7—C8	106.6 (4)
C3—N4—C5—C6	−2.3 (5)	C2—C3—C7—C8	−106.3 (3)
N4—C5—O50—C50	−3.5 (5)	C3—C7—C8—C9	−108.3 (4)
C6—C5—O50—C50	177.8 (3)	N4—C3—C8—C7	−106.3 (3)
C2—O1—C6—C61	142.9 (3)	C2—C3—C8—C7	104.2 (3)
C2—O1—C6—C5	25.4 (4)	N4—C3—C8—C9	6.2 (5)
C2—O1—C6—C62	−95.9 (4)	C2—C3—C8—C9	−143.2 (4)
N4—C5—C6—O1	−16.1 (5)	C7—C3—C8—C9	112.6 (4)
O50—C5—C6—O1	162.4 (3)	C7—C8—C9—O90	−98.3 (5)
N4—C5—C6—C61	−129.6 (4)	C3—C8—C9—O90	−170.9 (4)
O50—C5—C6—C61	48.9 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O90—H90···O21^i	0.82	1.94	2.757 (4)	174

Symmetry code: (i) x, y, z−1.

(II) dimethyl (1R,1'R,3'S,6'S)-[6'-tert-butyl-5'-methyoxy-6'-methyl-7'-oxa-8'-oxo- 4'-aza-spiro[2.5] oct-4'-en-1'-yl)hydroxymethylphosphonate

Crystal data

C15H26NO7P	F(000) = 388
Mr = 363.34	Dx = 1.290 Mg m^−3
Monoclinic, P21	Cu Kα radiation, λ = 1.54178 Å
a = 6.894 (1) Å	Cell parameters from 25 reflections
b = 9.423 (1) Å	θ = 22.9–27.1°
c = 14.428 (2) Å	µ = 1.61 mm^−1
β = 93.266 (10)°	T = 293 K
V = 935.8 (2) Å^3	Block, white
Z = 2	0.4 × 0.3 × 0.3 mm

Data collection

AFC5S Rigaku diffractometer	1578 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.018
Graphite monochromator	θmax = 67.5°, θmin = 5.6°
ω scan	h = −6→8
Absorption correction: analytical (De Meulenaer & Tompa, 1965)	k = −11→10
Tmin = 0.555, Tmax = 0.650	l = −17→17
1887 measured reflections	3 standard reflections every 150 reflections
1741 independent reflections	intensity decay: <2%

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.035	w = 1/[σ^2(Fo^2) + (0.0698P)^2 + 0.0119P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.102	(Δ/σ)max < 0.001
S = 1.08	Δρmax = 0.22 e Å^−3
1741 reflections	Δρmin = −0.26 e Å^−3
226 parameters	Extinction correction: SHELXL97, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
1 restraint	Extinction coefficient: 0.0119 (14)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983)
Secondary atom site location: difference Fourier map	Absolute structure parameter: 0.03 (3)

Special details

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 of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based

on F, with F set to zero for negative F². The threshold expression of

F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not 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 (Ų)

	x	y	z	Uiso*/Ueq
P1	0.79564 (12)	0.24272 (10)	−0.05426 (5)	0.0544 (2)
O30	0.8771 (5)	0.1094 (3)	−0.0854 (2)	0.0733 (8)
O10	0.5687 (3)	0.2403 (4)	−0.04970 (17)	0.0657 (6)
C100	0.4611 (7)	0.1103 (6)	−0.0421 (3)	0.0809 (13)
H10A	0.4457	0.0659	−0.1020	0.121*
H10B	0.3355	0.1308	−0.0199	0.121*
H10C	0.5302	0.0476	0.0005	0.121*
O20	0.8287 (4)	0.3741 (3)	−0.11823 (17)	0.0699 (7)
C200	0.7555 (7)	0.3735 (6)	−0.2125 (3)	0.0881 (14)
H20A	0.7997	0.2898	−0.2428	0.132*
H20B	0.8014	0.4561	−0.2435	0.132*
H20C	0.6161	0.3743	−0.2149	0.132*
C9	0.8899 (5)	0.3057 (4)	0.0578 (2)	0.0525 (7)
H9	0.8296	0.3970	0.0715	0.063*
O90	1.0937 (4)	0.3236 (3)	0.0550 (2)	0.0680 (7)
H91	1.1234	0.4043	0.0716	0.082*
C8	0.8447 (5)	0.1990 (4)	0.1319 (2)	0.0526 (7)
H8	0.9125	0.1079	0.1288	0.063*
C7	0.6450 (5)	0.1924 (4)	0.1660 (2)	0.0588 (9)
H7A	0.5939	0.0996	0.1806	0.071*
H7B	0.5493	0.2587	0.1396	0.071*
C3	0.8072 (4)	0.2514 (4)	0.22966 (19)	0.0497 (7)
C2	0.8757 (5)	0.1572 (4)	0.3060 (2)	0.0572 (9)
O21	0.8614 (6)	0.0291 (3)	0.3036 (2)	0.0815 (10)
O1	0.9517 (4)	0.2164 (3)	0.38443 (16)	0.0594 (6)
C6	0.9977 (5)	0.3670 (4)	0.3946 (2)	0.0514 (7)
C61	0.9262 (5)	0.4039 (5)	0.4895 (2)	0.0676 (10)
H61A	0.7897	0.3841	0.4902	0.101*
H61B	0.9485	0.5028	0.5019	0.101*
H61C	0.9953	0.3481	0.5362	0.101*
C62	1.2223 (5)	0.3823 (5)	0.3880 (2)	0.0609 (9)
C63	1.3266 (7)	0.2729 (8)	0.4514 (5)	0.126 (3)
H63A	1.2875	0.1791	0.4322	0.189*
H63B	1.2932	0.2883	0.5143	0.189*
H63C	1.4645	0.2826	0.4474	0.189*
C64	1.2768 (6)	0.3579 (8)	0.2897 (3)	0.1012 (19)
H64A	1.2267	0.4338	0.2510	0.152*
H64B	1.2227	0.2695	0.2675	0.152*
H64C	1.4157	0.3547	0.2879	0.152*
C65	1.2918 (7)	0.5306 (6)	0.4171 (4)	0.0885 (14)
H65A	1.4296	0.5374	0.4114	0.133*
H65B	1.2626	0.5474	0.4805	0.133*
H65C	1.2270	0.6001	0.3778	0.133*
C5	0.8858 (4)	0.4474 (4)	0.3192 (2)	0.0490 (7)
N4	0.8008 (4)	0.4017 (3)	0.24524 (18)	0.0485 (6)
O50	0.8819 (4)	0.5886 (3)	0.33880 (17)	0.0619 (6)
C50	0.7817 (7)	0.6787 (4)	0.2709 (3)	0.0732 (11)
H50A	0.8398	0.6688	0.2123	0.110*
H50B	0.7913	0.7757	0.2910	0.110*
H50C	0.6475	0.6515	0.2642	0.110*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
P1	0.0614 (5)	0.0517 (5)	0.0502 (4)	0.0004 (4)	0.0052 (3)	−0.0026 (4)
O30	0.097 (2)	0.0550 (17)	0.0686 (15)	0.0149 (14)	0.0084 (14)	−0.0178 (13)
O10	0.0584 (13)	0.0687 (15)	0.0696 (13)	−0.0068 (14)	−0.0013 (10)	0.0035 (15)
C100	0.084 (3)	0.087 (3)	0.071 (2)	−0.032 (2)	−0.007 (2)	−0.004 (2)
O20	0.0893 (18)	0.0656 (17)	0.0549 (13)	−0.0126 (14)	0.0043 (11)	0.0096 (12)
C200	0.099 (3)	0.103 (4)	0.061 (2)	0.000 (3)	−0.003 (2)	0.019 (2)
C9	0.0505 (16)	0.0517 (18)	0.0557 (16)	0.0002 (15)	0.0072 (13)	−0.0004 (15)
O90	0.0538 (13)	0.0723 (19)	0.0784 (17)	−0.0120 (12)	0.0071 (11)	−0.0032 (14)
C8	0.0597 (18)	0.0481 (18)	0.0505 (16)	−0.0021 (14)	0.0075 (13)	−0.0078 (13)
C7	0.0589 (18)	0.066 (2)	0.0516 (16)	−0.0149 (16)	0.0027 (14)	−0.0109 (16)
C3	0.0542 (15)	0.0486 (17)	0.0462 (14)	−0.0026 (16)	0.0025 (11)	−0.0057 (15)
C2	0.065 (2)	0.056 (3)	0.0505 (18)	−0.0027 (16)	0.0056 (15)	−0.0034 (15)
O21	0.128 (3)	0.0485 (18)	0.0671 (16)	−0.0120 (16)	−0.0016 (17)	−0.0017 (13)
O1	0.0724 (14)	0.0493 (15)	0.0550 (12)	−0.0078 (11)	−0.0087 (10)	0.0029 (10)
C6	0.0542 (17)	0.0510 (19)	0.0486 (15)	−0.0033 (15)	−0.0012 (12)	−0.0031 (14)
C61	0.070 (2)	0.083 (3)	0.0494 (17)	−0.012 (2)	0.0033 (15)	−0.0061 (18)
C62	0.0449 (16)	0.069 (2)	0.0675 (19)	0.0015 (16)	−0.0042 (14)	0.0025 (18)
C63	0.068 (3)	0.128 (6)	0.178 (6)	−0.001 (3)	−0.030 (3)	0.066 (5)
C64	0.053 (2)	0.156 (6)	0.096 (3)	−0.001 (3)	0.019 (2)	−0.033 (4)
C65	0.064 (2)	0.086 (3)	0.114 (4)	−0.023 (2)	0.002 (2)	−0.018 (3)
C5	0.0476 (17)	0.0477 (19)	0.0511 (16)	−0.0011 (14)	−0.0021 (13)	−0.0040 (14)
N4	0.0488 (14)	0.0471 (15)	0.0496 (13)	−0.0002 (11)	0.0019 (10)	−0.0043 (11)
O50	0.0730 (16)	0.0482 (13)	0.0630 (14)	0.0033 (12)	−0.0079 (12)	−0.0080 (12)
C50	0.090 (3)	0.050 (2)	0.077 (3)	0.0064 (19)	−0.009 (2)	0.0008 (19)

Geometric parameters (Å, º)

P1—O30	1.458 (3)	O1—C6	1.460 (4)
P1—O20	1.568 (3)	C6—C5	1.502 (5)
P1—O10	1.570 (2)	C6—C61	1.521 (5)
P1—C9	1.808 (3)	C6—C62	1.564 (5)
O10—C100	1.439 (5)	C61—H61A	0.9600
C100—H10A	0.9600	C61—H61B	0.9600
C100—H10B	0.9600	C61—H61C	0.9600
C100—H10C	0.9600	C62—C64	1.506 (6)
O20—C200	1.424 (5)	C62—C65	1.528 (6)
C200—H20A	0.9600	C62—C63	1.530 (6)
C200—H20B	0.9600	C63—H63A	0.9600
C200—H20C	0.9600	C63—H63B	0.9600
C9—O90	1.418 (4)	C63—H63C	0.9600
C9—C8	1.513 (4)	C64—H64A	0.9600
C9—H9	0.9800	C64—H64B	0.9600
O90—H91	0.8200	C64—H64C	0.9600
C8—C7	1.489 (5)	C65—H65A	0.9600
C8—C3	1.530 (4)	C65—H65B	0.9600
C8—H8	0.9800	C65—H65C	0.9600
C7—C3	1.513 (4)	C5—N4	1.264 (4)
C7—H7A	0.9700	C5—O50	1.361 (4)
C7—H7B	0.9700	O50—C50	1.442 (5)
C3—N4	1.436 (5)	C50—H50A	0.9600
C3—C2	1.472 (5)	C50—H50B	0.9600
C2—O21	1.211 (4)	C50—H50C	0.9600
C2—O1	1.341 (4)
O30—P1—O20	115.31 (16)	C2—O1—C6	124.2 (3)
O30—P1—O10	113.75 (18)	O1—C6—C5	108.5 (2)
O20—P1—O10	102.41 (16)	O1—C6—C61	103.5 (3)
O30—P1—C9	115.68 (17)	C5—C6—C61	110.9 (3)
O20—P1—C9	102.13 (15)	O1—C6—C62	107.1 (3)
O10—P1—C9	105.99 (14)	C5—C6—C62	112.2 (3)
C100—O10—P1	122.4 (3)	C61—C6—C62	114.0 (3)
O10—C100—H10A	109.5	C6—C61—H61A	109.5
O10—C100—H10B	109.5	C6—C61—H61B	109.5
H10A—C100—H10B	109.5	H61A—C61—H61B	109.5
O10—C100—H10C	109.5	C6—C61—H61C	109.5
H10A—C100—H10C	109.5	H61A—C61—H61C	109.5
H10B—C100—H10C	109.5	H61B—C61—H61C	109.5
C200—O20—P1	120.3 (3)	C64—C62—C65	107.9 (4)
O20—C200—H20A	109.5	C64—C62—C63	109.0 (5)
O20—C200—H20B	109.5	C65—C62—C63	108.8 (4)
H20A—C200—H20B	109.5	C64—C62—C6	110.2 (3)
O20—C200—H20C	109.5	C65—C62—C6	111.3 (3)
H20A—C200—H20C	109.5	C63—C62—C6	109.5 (3)
H20B—C200—H20C	109.5	C62—C63—H63A	109.5
O90—C9—C8	110.1 (3)	C62—C63—H63B	109.5
O90—C9—P1	108.6 (2)	H63A—C63—H63B	109.5
C8—C9—P1	109.6 (2)	C62—C63—H63C	109.5
O90—C9—H9	109.5	H63A—C63—H63C	109.5
C8—C9—H9	109.5	H63B—C63—H63C	109.5
P1—C9—H9	109.5	C62—C64—H64A	109.5
C9—O90—H91	109.5	C62—C64—H64B	109.5
C7—C8—C9	119.5 (3)	H64A—C64—H64B	109.5
C7—C8—C3	60.1 (2)	C62—C64—H64C	109.5
C9—C8—C3	119.3 (3)	H64A—C64—H64C	109.5
C7—C8—H8	115.5	H64B—C64—H64C	109.5
C9—C8—H8	115.5	C62—C65—H65A	109.5
C3—C8—H8	115.5	C62—C65—H65B	109.5
C8—C7—C3	61.3 (2)	H65A—C65—H65B	109.5
C8—C7—H7A	117.6	C62—C65—H65C	109.5
C3—C7—H7A	117.6	H65A—C65—H65C	109.5
C8—C7—H7B	117.6	H65B—C65—H65C	109.5
C3—C7—H7B	117.6	N4—C5—O50	119.6 (3)
H7A—C7—H7B	114.7	N4—C5—C6	129.4 (3)
N4—C3—C2	119.3 (3)	O50—C5—C6	111.0 (3)
N4—C3—C7	115.4 (3)	C5—N4—C3	116.8 (3)
C2—C3—C7	115.3 (3)	C5—O50—C50	116.7 (3)
N4—C3—C8	118.1 (3)	O50—C50—H50A	109.5
C2—C3—C8	115.6 (3)	O50—C50—H50B	109.5
C7—C3—C8	58.6 (2)	H50A—C50—H50B	109.5
O21—C2—O1	117.8 (3)	O50—C50—H50C	109.5
O21—C2—C3	123.8 (3)	H50A—C50—H50C	109.5
O1—C2—C3	118.3 (3)	H50B—C50—H50C	109.5
O30—P1—O10—C100	22.2 (3)	C8—C3—C2—O1	142.4 (3)
O20—P1—O10—C100	147.3 (3)	O21—C2—O1—C6	173.0 (4)
C9—P1—O10—C100	−106.1 (3)	C3—C2—O1—C6	−9.4 (5)
O30—P1—O20—C200	59.9 (4)	C2—O1—C6—C5	19.5 (4)
O10—P1—O20—C200	−64.1 (3)	C2—O1—C6—C61	137.4 (3)
C9—P1—O20—C200	−173.8 (3)	C2—O1—C6—C62	−101.8 (3)
O30—P1—C9—O90	58.6 (3)	O1—C6—C62—C64	71.8 (4)
O20—P1—C9—O90	−67.5 (3)	C5—C6—C62—C64	−47.2 (5)
O10—P1—C9—O90	−174.3 (3)	C61—C6—C62—C64	−174.4 (4)
O30—P1—C9—C8	−61.7 (3)	O1—C6—C62—C65	−168.5 (3)
O20—P1—C9—C8	172.2 (2)	C5—C6—C62—C65	72.5 (4)
O10—P1—C9—C8	65.4 (3)	C61—C6—C62—C65	−54.7 (4)
O90—C9—C8—C7	163.0 (3)	O1—C6—C62—C63	−48.1 (5)
P1—C9—C8—C7	−77.6 (3)	C5—C6—C62—C63	−167.1 (4)
O90—C9—C8—C3	92.8 (3)	C61—C6—C62—C63	65.7 (5)
P1—C9—C8—C3	−147.8 (2)	O1—C6—C5—N4	−15.8 (5)
C9—C8—C7—C3	−108.9 (3)	C61—C6—C5—N4	−128.8 (4)
C8—C7—C3—N4	108.7 (3)	C62—C6—C5—N4	102.4 (4)
C8—C7—C3—C2	−105.8 (3)	O1—C6—C5—O50	164.0 (3)
C7—C8—C3—N4	−104.2 (3)	C61—C6—C5—O50	50.9 (4)
C9—C8—C3—N4	5.1 (4)	C62—C6—C5—O50	−77.8 (3)
C7—C8—C3—C2	105.3 (4)	O50—C5—N4—C3	−178.8 (3)
C9—C8—C3—C2	−145.5 (3)	C6—C5—N4—C3	0.9 (5)
C9—C8—C3—C7	109.2 (4)	C2—C3—N4—C5	11.9 (4)
N4—C3—C2—O21	169.5 (4)	C7—C3—N4—C5	156.0 (3)
C7—C3—C2—O21	25.4 (5)	C8—C3—N4—C5	−137.6 (3)
C8—C3—C2—O21	−40.3 (5)	N4—C5—O50—C50	−1.3 (5)
N4—C3—C2—O1	−7.8 (5)	C6—C5—O50—C50	178.9 (3)
C7—C3—C2—O1	−152.0 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O90—H91···O30^i	0.82	1.95	2.735 (4)	161

Symmetry code: (i) −x+2, y+1/2, −z.