Two new conformationally restricted 4,5-dihydroxynorvaline analogues with a norbornane skeleton

The structures of two conformationally restricted 4,5-di­hydroxy­norvaline analogues with a norbornane skeleton, namely methyl (1S,2S,3R,4R)-2-benz­amido-3-(1,2-di­hydroxy­ethyl)­bi­cyclo[2.2.1]­heptane-2-carboxyl­ate, C₁₈H₂₃NO₅, and methyl (1R,2S,3R,4S)-2-benz­amido-3-(1,2-di­hydroxy­ethyl)­bi­cyclo[2.2.1]­heptane-2-carboxyl­ate, C₁₈H₂₃NO₅, exhibit a conformation in the helical region of the φ,ψ map but their handedness is opposite. In both cases, the torsion angles (χ^1,1) giving the relative orientation of the 1,2-di­hydroxy­ethyl group of the amino acid side chain and the benz­amide group of the peptide chain indicate that these groups adopt a nearly eclipsed conformation. Both compounds show a complex hydrogen-bonding pattern.

S1. Comment

Amino acids containing one or more hydroxy groups form an important class of naturally occurring compounds (Hunt, 1985). Such compounds, whether of natural or synthetic origin, are useful precursors in the synthesis of β-lactams (Miller, 1986). An important example is (2S,4S)-4,5-dihydroxynorvaline (Liao & Zhou, 1998; Girard et al., 1998), which is a key intermediate in the synthesis of antibiotic clavalanine.

For some years, we have been focusing our attention on those amino acids that possess specific conformational and topographical modifications on their side-chain and, in particular, cyclization of the side-chain atoms with the main-chain atoms. This structural modification can result in significant changes in potency, receptor selectivity and biostability when incorporated into bioactive compounds. Recently, we reported our findings on the asymmetric Diels-Alder reaction between (Z)-2-phenyl-4-[(S)-2,2-dimethyl- 1,3-dioxolan-4-ylmethylene]-5-(4H)-oxazolone and cyclopentadiene. The corresponding exo/endo adducts were isolated in enantiomerically pure form and transformed into two new conformationally constrained 4,5-dihydroxynorvaline analogues with a norbornane skeleton (Buñuel et al., 1996a), methyl (1S,2S,3R,4R)-2-benzamido-3-(1,2-dihydroxyethyl)bicyclo [2.2.1]heptane-2-carboxylate, exo-(I), and methyl (1R,2S,3R,4S)-2-benzamido-3-(1,2-dihydroxyethyl)bicyclo[2.2.1]heptane-2- carboxylate, endo-(I). We describe here the crystal and molecular structures of these two new diastereomeric amino acids. \scheme

Compound exo-(I) crystallizes with two molecules (A and B) in the asymmetric unit (Fig. 1). The numbering of the atoms runs from 1 to 18 for the first molecule and from 19 to 36 for the second. These two independent molecules differ slightly in their conformation. The main difference between them is the orientation of the phenyl group, with N1—C10—C11—C12 and O3—C10—C11—C16 torsion angles of 7.7 (5) and 3.6 (5)° for molecule A and N2—C28—C29—C30 and O8—C28—C29—C34 torsion angles of -28.6 (5) and -30.5 (6)° for molecule B. The configuration at the chiral atoms C1, C2, C3, C4 and C17 for the first conformer and at chiral atoms C19, C20, C21, C22 and C35 for the second are S, S, R, R and S, respectively. The bond lengths and angles show small variations from reported values for other norbornane amino acid derivatives (Apgar & Ludwig, 1972; Glass et al., 1990; Buñuel et al., 1996b; Buñuel et al., 1997). The C4—C7—C1 and C19—C25—C22 angles of 94.2 (3) and 93.3 (3)°, respectively, are significantly contracted with respect to the regular tetrahedral value, while the endocyclic angles of the five-membered norbornane rings are in the range 98.7 (4)–105.7 (5)°. The values for the conformationally sensitive N—C^α—C' (τ) bond angles [N1—C2—C8 = 109.5 (3)° and N2—C20—C26 = 108.3 (3)°], which are external to the cyclic system, are very close to the tetrahedral value, as would be expected for the C^α,^α-dialkylated glycines that form regular helices (Benedetti et al., 1997).

In the bicyclo[2.2.1]heptane (norbornane) unit of each independent molecule, the two five-membered rings are in envelope conformations, while the six-membered ring adopts an approximate boat conformation. The slightly distorted boat conformation of the norbornane six-membered rings, C1—C6 and C19—C24, is evidenced by the puckering parameters (Cremer & Pople, 1975): q₂ = 0.919 (4) Å, q₃ = 0.022 (4) Å, ϕ₂ = 2.7 (3)°, θ₂ = 88,6(2)° and Θ_T = 0.919 (4) Å, and q₂ = 0.928 (5) Å, q₃ = 0.026 (5) Å, ϕ₂ = 4.2 (3)°, θ₂ = 88.4 (3)° and Θ_T = 0.929 (5) Å, respectively. In both independent molecules, the substitution of the norbornane ring produces a twist of type S-(+,+) (Altona & Sundaralingam, 1970) about the C1···C4 or C19···C22 vectors. The twisting can be seen from the C1—C2—C3—C4 and C4—C5—C6—C1 torsion angles of 4.5 (3) and 0.8 (4)°, respectively, for molecule A, and from the C19—C20—C21—C22 and C22—C23—C24—C19 torsion angles of 6.5 (4) and 2.6 (5)°, respectively, for molecule B.

In compound exo-(I), the amino acid residue adopts a folded conformation. The values of the backbone torsion angles ϕ [C10—N1—C2—C8 = -52.3 (5)° for molecule A and C28—N2—C20—C26 = -52.4 (5)° for molecule B] and ψ [N1—C2—C8—O2 = -47.1 (4)° for molecule A and N2—C20—C26—O6 = -42.7 (4)° for molecule B] fall in the A region of the conformational map (Zimmerman et al., 1977). These values differ by less than 20° from those pertaining to the ideal 3₁₀-helix (60, 30°) or α-helix (55, 45°). The torsion angles ω [C11—C10—N1—C2 = 177.3 (3)° and C29—C28—N2—C20 = 176.1 (3)°] indicate that the amide linkage adopts the usual trans conformation in both conformers. The spatial arrangement of the 1,2-dihydroxyethyl group of the amino acid side-chain with respect to the peptide chain is defined by the torsion angles χ^1,1 [N1—C2—C3—C17 = 15.8 (4)° for molecule A and N2—C20—C21—C35 = 16.9 (5)° for molecule B]. These values indicate that the benzamide and 1,2-dihydroxyethyl groups are in a nearly eclipsed conformation. In addition, both groups are involved in an N—H···O intramolecular hydrogen bond with an N1···O4 distance of 2.712 (4) Å for the first independent molecule and an N2···O9 distance of 2.698 (4) Å for the second. Another short intramolecular contact is observed between the two hydroxy groups [O4···O5 2.857 (4) and O9···O10 2.874 (4) Å].

In the crystals of compound exo-(I), the two independent molecules of the asymmetric unit form dimers in which two hydrogen bonds are observed between the O4—H4O donor of molecule A and the O10 acceptor of molecule B, with a distance of 2.714 (4) Å, and between the O9—H9O donor of molecule B and the O5 acceptor of molecule A, with a distance of 2.783 (4) Å. Moreover, the crystal structure is stabilized by two additional O—H···O intermolecular hydrogen bonds, involving the terminal hydroxy group of each independent molecule and the benzamide group of a symmetry-related molecule of the same type (A or B) [O5···O3 2.739 (4) Å and O10···O8 2.673 (4) Å]. Both hydroxy groups function as hydrogen-bond donors, whereby the molecules are linked into sheets parallel to the z axis (Fig. 2). Some short intra- and intermolecular C—H···O contacts (Table 2) are also found, which can be described as weak hydrogen bonds (Steiner, 1997; Desiraju, 1996).

Diastereoisomer endo-(I) crystallizes with one molecule in the asymmetry unit (Fig. 3). The stereochemistry at the chiral C1, C2, C3, C4 and C17 atoms is R, S, R, S and S, respectively. Comparison of the bond distances and angles in compound endo-(I) with those determined for other norbornane amino acids, and in particular with the compound exo-(I), reveals no strikingly unusual features and these parameters lie within the expected ranges. The C4—C7—C1 angle is 94.5 (2)° and the endocyclic angles of the five-membered norbornane rings vary from 101.2 (2) to 103.2 (2)°, which are all substantially less than the regular tetrahedral value of 109.5°. The critical intra-ring bond angle τ [N—C2—C8 = 109.48 (17)°] is comparable with that in compound exo-(I).

The two five-membered norbornane rings of compound endo-(I) are in envelope conformations, while the six-membered norbornane ring is in an almost perfect boat conformation [puckering parameters are q₂ = 0.958 (9) Å, q₃ = 0.051 (3) Å, query Chester PLATON gives 0.005 (3) ϕ₂ = 179.51 (17)°, θ₂ = 89.69 (15)° and Θ_T = 0.958 (9) Å]. The norbornane system shows a weak distortion from C_2ν symmetry, although it is less important than in exo-(I). The twisting can be seen from the C1—C2—C3—C4 and C4—C5—C6—C1 torsion angles of 1.4 (2) and 0.0 (3)°, respectively.

The amino acid residue in compound endo-(I) exhibits a conformation in the helical region of the ϕ,ψ map, but it has opposite handedness to that shown by compound exo-(I): the values of the backbone torsion angles ϕ [C10—N—C2—C8 = 42.8 (3)°] and ψ [N—C2—C8—O2 = 50.1 (2)°] fall in the A* region of the conformational map (Zimmerman et al., 1977). The torsion angle ω (C11—C10—N—C2) differs by less than 10° from 180°, the ideal value of the trans planar amide unit. In compound endo-(I), the torsion angle χ^1,1 [N—C2—C3—C17 = 9.8 (3)°] also shows that the 1,2-dihydroxyethyl and benzamide groups are in a nearly eclipsed conformation. However, in contrast with exo-(I), no intramolecular hydrogen bond is observed between these two groups, whereas the short intramolecular contact involving both hydroxy groups observed in compound exo-(I) is also present in compound endo-(I) [O4···O5 2.787 (3) Å].

Apart from the spatial arrangement of the methyl ester and the benzamido and 1,2-dihydroxyethyl groups relative to the norbornane ring, the main difference between the 4,5-dihydroxynorvaline analogues described here, i.e. endo-(I) and exo-(I), involves the intermolecular hydrogen-bond pattern. In the crystals of endo-(I) three intermolecular hydrogen bonds are seen: one weak O(hydroxy)-H···O/N(amide/methyl ester) three-centre hydrogen bond [O4···N 3.239 (3) Å and O4···O2 3.026 (2) Å], one O(hydroxy)-H···O=C(amide) two-centre hydrogen bond [O5···O3 2.728 (3) Å] and one N(amide)-H···O(hydroxy) two-centre hydrogen bond [N···O5 2.917 (3) Å]. Both OH and NH groups function as hydrogen-bond donors, whereby the molecules are linked into sheets parallel to the z axis (Fig. 4). As in the diastereoisomer exo-(I), some possible borderline cases of C—H···O hydrogen bonds are also present in endo-(I) (Table 4).

S2. Experimental

Compounds exo-(I) and endo-(I) were prepared according to the procedure previously described by Buñuel et al. (1996a). Crystals were obtained by slow evaporation of a methanol solution.

S3. Refinement

The absolute configuration of compounds exo-(I) and endo-(I) was deduced from the known stereochemistry of the chiral centre at C17 [for conformer A of exo-(I) and for endo-(I)] or C35 [for conformer B of exo-(I)], which was derived from the (R)—O,O-isopropylideneglyceraldehyde starting material. H atoms bonded to N or O were located from Fourier syntheses and refined freely, methyl group H atoms were refined as rigid groups (initial position from Fourier syntheses, allowed to rotate but not tip) and the remaining H atoms were treated as riding. All H atoms bonded to C were refined with fixed individual displacement parameters [U_iso(H) = 1.5U_eq(C_methyl) or 1.2U_eq(C)]. Molecular geometry calculations were performed using PARST (Nardelli, 1983).

Computing details

For both compounds, data collection: XSCANS (Siemens, 1993); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SIR92 (Altomare et al., 1993); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL-Plus (Sheldrick, 1989); software used to prepare material for publication: SHELXL97.

Figures

	Fig. 1. The molecular structure of the two conformers forming the asymmetric unit of exo-(I). Displacement ellipsoids are drawn at the 30% probability level and intramolecular hydrogen bonds are indicated by dashed lines. H atoms are shown as spheres of arbitrary radii.
	Fig. 2. Packing diagram for exo-(I) viewed parallel to the z axis. H atoms not involved in hydrogen bonds have been omitted for clarity. Hydrogen bonds are indicated by dashed bonds.
	Fig. 3. The molecular structure of endo-(I). Displacement ellipsoids are drawn at the 30% probability level and the intramolecular hydrogen bond is indicated by a dashed line. H atoms are shown as spheres of arbitrary radii.
	Fig. 4. Packing diagram for endo-(I) viewed parallel to the z axis. H atoms not involved in hydrogen bonds have been omitted for clarity. Hydrogen bonds are indicated by dashed bonds.

(exoI) methyl (1S,2S,3R,4R)-2-benzamido-3-(1,2-dihydroxyethyl)bicyclo [2.2.1]heptane-2-carboxylate

Crystal data

C18H23NO5	F(000) = 712
Mr = 333.37	Dx = 1.253 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
a = 9.323 (5) Å	Cell parameters from 38 reflections
b = 18.038 (5) Å	θ = 7.2–12.5°
c = 10.968 (5) Å	µ = 0.09 mm^−1
β = 106.570 (5)°	T = 293 K
V = 1767.9 (13) Å^3	Prism, colourless
Z = 4	0.64 × 0.32 × 0.10 mm

Data collection

Siemens P4 diffractometer	θmax = 25.0°, θmin = 2.2°
ω/2θ scans	h = −1→11
7359 measured reflections	k = −21→21
3213 independent reflections	l = −13→12
2274 reflections with I > 2σ(I)	3 standard reflections every 97 reflections
Rint = 0.047	intensity decay: none

Refinement

Refinement on F^2	459 parameters
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.040	w = 1/[σ^2(Fo^2) + (0.0422P)^2 + 0.0448P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.093	(Δ/σ)max < 0.001
S = 1.05	Δρmax = 0.13 e Å^−3
3213 reflections	Δρmin = −0.16 e Å^−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
O1	0.7287 (4)	−0.1145 (3)	−0.1892 (3)	0.1053 (12)
O2	0.7676 (3)	−0.05323 (16)	−0.0069 (3)	0.0662 (7)
O3	0.6899 (3)	−0.21963 (14)	0.0485 (3)	0.0632 (7)
O4	0.3258 (3)	−0.02027 (15)	0.0424 (2)	0.0522 (6)
H4O	0.317 (4)	0.007 (2)	0.098 (4)	0.058 (13)*
O5	0.3518 (4)	0.13752 (18)	0.0391 (3)	0.0742 (9)
H5O	0.325 (6)	0.180 (3)	0.022 (5)	0.11 (2)*
N1	0.5299 (4)	−0.12577 (17)	0.0338 (3)	0.0488 (8)
H1A	0.465 (4)	−0.104 (2)	0.061 (3)	0.041 (10)*
C1	0.4350 (5)	−0.1557 (3)	−0.2016 (3)	0.0664 (11)
H1	0.4895	−0.1993	−0.2179	0.080*
C2	0.5259 (4)	−0.1035 (2)	−0.0953 (3)	0.0499 (9)
C3	0.4405 (4)	−0.0275 (2)	−0.1304 (3)	0.0491 (8)
H3	0.5052	0.0030	−0.1667	0.059*
C4	0.3063 (5)	−0.0484 (3)	−0.2442 (3)	0.0677 (12)
H4	0.2577	−0.0059	−0.2950	0.081*
C5	0.1996 (5)	−0.0998 (3)	−0.2059 (4)	0.0869 (15)
H5A	0.1077	−0.1057	−0.2742	0.104*
H5B	0.1756	−0.0816	−0.1308	0.104*
C6	0.2856 (6)	−0.1720 (3)	−0.1786 (4)	0.0837 (15)
H6B	0.2990	−0.1874	−0.0913	0.100*
H6A	0.2332	−0.2109	−0.2350	0.100*
C7	0.3821 (5)	−0.1012 (3)	−0.3151 (3)	0.0745 (13)
H7A	0.4646	−0.0784	−0.3387	0.089*
H7B	0.3125	−0.1237	−0.3889	0.089*
C8	0.6848 (5)	−0.0932 (2)	−0.1033 (4)	0.0621 (10)
C9	0.9158 (5)	−0.0336 (3)	−0.0135 (5)	0.0899 (15)
H9A	0.9656	−0.0772	−0.0312	0.135*
H9B	0.9723	−0.0127	0.0662	0.135*
H9C	0.9078	0.0021	−0.0801	0.135*
C10	0.6090 (4)	−0.18197 (19)	0.0963 (3)	0.0473 (9)
C11	0.6057 (4)	−0.19496 (19)	0.2299 (3)	0.0478 (9)
C12	0.5133 (5)	−0.1578 (3)	0.2862 (4)	0.0718 (12)
H12	0.4445	−0.1240	0.2385	0.086*
C13	0.5199 (7)	−0.1692 (3)	0.4116 (5)	0.0909 (16)
H13	0.4560	−0.1434	0.4479	0.109*
C14	0.6218 (7)	−0.2191 (3)	0.4832 (4)	0.0931 (16)
H14	0.6301	−0.2253	0.5691	0.112*
C15	0.7093 (6)	−0.2587 (3)	0.4285 (5)	0.0900 (15)
H15	0.7750	−0.2938	0.4759	0.108*
C16	0.7017 (5)	−0.2474 (3)	0.3025 (4)	0.0730 (12)
H16	0.7619	−0.2754	0.2656	0.088*
C17	0.4155 (4)	0.01862 (19)	−0.0218 (3)	0.0481 (9)
H17	0.5134	0.0274	0.0395	0.058*
C18	0.3478 (5)	0.0933 (2)	−0.0680 (4)	0.0618 (10)
H18A	0.4042	0.1170	−0.1192	0.074*
H18B	0.2452	0.0871	−0.1201	0.074*
O6	0.8972 (3)	−0.03543 (15)	0.3137 (2)	0.0661 (7)
O7	1.0372 (4)	−0.0274 (2)	0.5124 (3)	0.1154 (14)
O8	1.0850 (3)	0.10855 (18)	0.3249 (3)	0.0734 (8)
O9	0.5477 (3)	0.13015 (15)	0.2834 (2)	0.0584 (7)
H9O	0.461 (6)	0.130 (4)	0.218 (5)	0.14 (2)*
O10	0.3020 (3)	0.03100 (19)	0.2684 (3)	0.0665 (8)
H10O	0.235 (5)	0.063 (2)	0.271 (4)	0.064 (13)*
N2	0.8424 (4)	0.11040 (19)	0.3119 (3)	0.0547 (8)
H2A	0.760 (4)	0.1286 (19)	0.281 (3)	0.031 (9)*
C19	0.9400 (5)	0.1147 (3)	0.5519 (4)	0.0766 (13)
H19	1.0494	0.1129	0.5732	0.092*
C20	0.8598 (4)	0.0702 (2)	0.4305 (3)	0.0563 (10)
C21	0.7045 (4)	0.0523 (2)	0.4536 (3)	0.0585 (10)
H21	0.7109	0.0002	0.4797	0.070*
C22	0.7109 (5)	0.0969 (3)	0.5760 (4)	0.0847 (15)
H22	0.6362	0.0826	0.6189	0.102*
C23	0.7207 (7)	0.1790 (4)	0.5531 (5)	0.106 (2)
H23A	0.7054	0.2072	0.6236	0.128*
H23B	0.6456	0.1937	0.4757	0.128*
C24	0.8779 (7)	0.1920 (3)	0.5408 (5)	0.1005 (17)
H24A	0.8746	0.2140	0.4594	0.121*
H24B	0.9361	0.2236	0.6086	0.121*
C25	0.8777 (5)	0.0802 (3)	0.6526 (4)	0.0878 (16)
H25A	0.9091	0.1060	0.7335	0.105*
H25B	0.8990	0.0277	0.6645	0.105*
C26	0.9437 (5)	−0.0016 (2)	0.4249 (4)	0.0641 (11)
C27	0.9732 (6)	−0.1038 (3)	0.3028 (5)	0.0909 (15)
H27A	1.0759	−0.0934	0.3083	0.136*
H27B	0.9255	−0.1266	0.2224	0.136*
H27C	0.9688	−0.1367	0.3705	0.136*
C28	0.9550 (4)	0.1257 (2)	0.2659 (4)	0.0559 (10)
C29	0.9175 (4)	0.1628 (2)	0.1393 (3)	0.0536 (9)
C30	0.7819 (5)	0.1536 (2)	0.0480 (4)	0.0650 (11)
H30	0.7104	0.1220	0.0640	0.078*
C31	0.7509 (5)	0.1908 (3)	−0.0671 (4)	0.0749 (12)
H31	0.6590	0.1839	−0.1275	0.090*
C32	0.8538 (5)	0.2372 (3)	−0.0927 (4)	0.0773 (13)
H32	0.8325	0.2625	−0.1697	0.093*
C33	0.9890 (6)	0.2461 (3)	−0.0034 (5)	0.0866 (14)
H33	1.0600	0.2776	−0.0203	0.104*
C34	1.0218 (5)	0.2093 (3)	0.1112 (4)	0.0750 (13)
H34	1.1148	0.2157	0.1703	0.090*
C35	0.5630 (4)	0.0576 (2)	0.3413 (3)	0.0500 (9)
H35	0.5716	0.0213	0.2773	0.060*
C36	0.4254 (4)	0.0393 (2)	0.3801 (3)	0.0600 (10)
H36A	0.4407	−0.0063	0.4290	0.072*
H36B	0.4047	0.0787	0.4330	0.072*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.087 (2)	0.165 (4)	0.076 (2)	0.001 (3)	0.0422 (18)	−0.029 (2)
O2	0.0511 (15)	0.0775 (19)	0.0725 (17)	0.0027 (15)	0.0215 (13)	−0.0032 (15)
O3	0.0692 (18)	0.0518 (15)	0.0747 (17)	0.0117 (14)	0.0303 (15)	−0.0032 (13)
O4	0.0542 (15)	0.0553 (16)	0.0504 (15)	0.0044 (13)	0.0203 (12)	−0.0010 (13)
O5	0.097 (2)	0.0529 (17)	0.0636 (18)	0.0233 (18)	0.0075 (16)	0.0024 (14)
N1	0.0518 (19)	0.0522 (19)	0.0437 (17)	0.0105 (17)	0.0156 (15)	−0.0010 (14)
C1	0.083 (3)	0.065 (2)	0.051 (2)	−0.002 (2)	0.018 (2)	−0.0139 (19)
C2	0.055 (2)	0.055 (2)	0.0403 (18)	0.0048 (19)	0.0153 (16)	−0.0014 (17)
C3	0.049 (2)	0.056 (2)	0.0428 (17)	0.0011 (19)	0.0141 (15)	0.0078 (16)
C4	0.069 (3)	0.084 (3)	0.0403 (19)	0.003 (3)	−0.0007 (19)	0.000 (2)
C5	0.068 (3)	0.121 (4)	0.064 (3)	−0.022 (3)	0.006 (2)	−0.014 (3)
C6	0.092 (4)	0.095 (4)	0.056 (3)	−0.040 (3)	0.008 (2)	−0.004 (2)
C7	0.090 (3)	0.095 (3)	0.038 (2)	−0.014 (3)	0.018 (2)	−0.009 (2)
C8	0.063 (3)	0.074 (3)	0.053 (2)	0.011 (2)	0.023 (2)	0.000 (2)
C9	0.056 (3)	0.104 (4)	0.116 (4)	−0.002 (3)	0.035 (3)	0.002 (3)
C10	0.044 (2)	0.042 (2)	0.054 (2)	−0.0003 (18)	0.0102 (17)	−0.0059 (17)
C11	0.049 (2)	0.0401 (19)	0.051 (2)	−0.0025 (18)	0.0094 (17)	0.0015 (16)
C12	0.093 (3)	0.063 (2)	0.065 (3)	0.015 (3)	0.031 (2)	0.016 (2)
C13	0.138 (5)	0.080 (3)	0.074 (3)	0.008 (3)	0.060 (3)	0.009 (3)
C14	0.116 (4)	0.106 (4)	0.054 (3)	−0.011 (4)	0.020 (3)	0.020 (3)
C15	0.085 (3)	0.101 (4)	0.075 (3)	0.015 (3)	0.008 (3)	0.030 (3)
C16	0.064 (3)	0.081 (3)	0.068 (3)	0.010 (3)	0.009 (2)	0.011 (2)
C17	0.045 (2)	0.048 (2)	0.0466 (18)	0.0064 (18)	0.0054 (16)	0.0052 (16)
C18	0.064 (3)	0.057 (2)	0.055 (2)	0.009 (2)	0.0023 (19)	0.0078 (19)
O6	0.0616 (16)	0.0592 (17)	0.0652 (16)	0.0082 (15)	−0.0017 (13)	−0.0054 (14)
O7	0.118 (3)	0.122 (3)	0.0713 (19)	0.062 (3)	−0.0285 (19)	−0.004 (2)
O8	0.0373 (15)	0.102 (2)	0.0743 (17)	0.0130 (16)	0.0048 (13)	−0.0099 (16)
O9	0.0462 (15)	0.0624 (16)	0.0583 (15)	0.0068 (14)	0.0014 (13)	0.0070 (13)
O10	0.0434 (15)	0.093 (2)	0.0628 (16)	0.0065 (16)	0.0150 (13)	−0.0142 (15)
N2	0.0351 (17)	0.066 (2)	0.0563 (19)	0.0074 (17)	0.0019 (15)	0.0045 (16)
C19	0.063 (3)	0.090 (4)	0.060 (3)	0.005 (3)	−0.009 (2)	−0.014 (2)
C20	0.056 (2)	0.059 (2)	0.0439 (19)	0.007 (2)	−0.0019 (17)	−0.0005 (18)
C21	0.058 (2)	0.069 (2)	0.0433 (19)	0.005 (2)	0.0057 (17)	0.0074 (18)
C22	0.076 (3)	0.130 (5)	0.046 (2)	0.012 (3)	0.014 (2)	−0.010 (2)
C23	0.101 (4)	0.122 (5)	0.078 (3)	0.042 (4)	−0.004 (3)	−0.041 (3)
C24	0.111 (5)	0.092 (4)	0.079 (3)	0.012 (4)	−0.003 (3)	−0.030 (3)
C25	0.084 (3)	0.121 (4)	0.046 (2)	0.019 (3)	−0.001 (2)	−0.004 (2)
C26	0.057 (2)	0.074 (3)	0.051 (2)	0.015 (2)	−0.0027 (19)	0.003 (2)
C27	0.094 (4)	0.060 (3)	0.104 (4)	0.012 (3)	0.005 (3)	−0.015 (3)
C28	0.039 (2)	0.060 (2)	0.064 (2)	0.0054 (19)	0.0092 (18)	−0.0134 (19)
C29	0.043 (2)	0.060 (2)	0.060 (2)	−0.001 (2)	0.0177 (18)	−0.0108 (18)
C30	0.058 (3)	0.077 (3)	0.059 (2)	−0.016 (2)	0.014 (2)	−0.004 (2)
C31	0.071 (3)	0.094 (3)	0.057 (3)	−0.015 (3)	0.014 (2)	−0.007 (2)
C32	0.081 (3)	0.090 (3)	0.067 (3)	−0.006 (3)	0.032 (3)	0.005 (2)
C33	0.075 (3)	0.095 (4)	0.100 (4)	−0.012 (3)	0.041 (3)	0.011 (3)
C34	0.052 (2)	0.088 (3)	0.084 (3)	−0.005 (2)	0.018 (2)	0.000 (3)
C35	0.046 (2)	0.055 (2)	0.0452 (18)	0.0077 (19)	0.0071 (15)	0.0025 (17)
C36	0.049 (2)	0.079 (3)	0.052 (2)	0.009 (2)	0.0148 (18)	−0.001 (2)

Geometric parameters (Å, º)

O1—C8	1.192 (5)	O6—C26	1.322 (4)
O2—C8	1.330 (5)	O6—C27	1.444 (5)
O2—C9	1.449 (5)	O7—C26	1.192 (4)
O3—C10	1.237 (4)	O8—C28	1.239 (4)
O4—C17	1.422 (4)	O9—C35	1.444 (5)
O4—H4O	0.81 (4)	O9—H9O	0.92 (6)
O5—C18	1.412 (5)	O10—C36	1.430 (4)
O5—H5O	0.81 (6)	O10—H10O	0.86 (4)
N1—C10	1.324 (4)	N2—C28	1.317 (5)
N1—C2	1.463 (4)	N2—C20	1.458 (5)
N1—H1A	0.85 (3)	N2—H2A	0.82 (3)
C1—C6	1.514 (6)	C19—C24	1.502 (8)
C1—C2	1.549 (5)	C19—C25	1.519 (6)
C1—C7	1.552 (6)	C19—C20	1.552 (5)
C1—H1	0.9800	C19—H19	0.9800
C2—C8	1.520 (5)	C20—C26	1.524 (6)
C2—C3	1.577 (5)	C20—C21	1.573 (5)
C3—C17	1.524 (5)	C21—C35	1.530 (5)
C3—C4	1.541 (5)	C21—C22	1.551 (6)
C3—H3	0.9800	C21—H21	0.9800
C4—C5	1.504 (6)	C22—C23	1.509 (8)
C4—C7	1.524 (6)	C22—C25	1.572 (6)
C4—H4	0.9800	C22—H22	0.9800
C5—C6	1.514 (7)	C23—C24	1.528 (8)
C5—H5A	0.9700	C23—H23A	0.9700
C5—H5B	0.9700	C23—H23B	0.9700
C6—H6B	0.9700	C24—H24A	0.9700
C6—H6A	0.9700	C24—H24B	0.9700
C7—H7A	0.9700	C25—H25A	0.9700
C7—H7B	0.9700	C25—H25B	0.9700
C9—H9A	0.9600	C27—H27A	0.9600
C9—H9B	0.9600	C27—H27B	0.9600
C9—H9C	0.9600	C27—H27C	0.9600
C10—C11	1.492 (5)	C28—C29	1.490 (5)
C11—C12	1.371 (6)	C29—C30	1.381 (5)
C11—C16	1.386 (5)	C29—C34	1.383 (5)
C12—C13	1.374 (6)	C30—C31	1.386 (6)
C12—H12	0.9300	C30—H30	0.9300
C13—C14	1.380 (7)	C31—C32	1.361 (6)
C13—H13	0.9300	C31—H31	0.9300
C14—C15	1.347 (7)	C32—C33	1.367 (7)
C14—H14	0.9300	C32—H32	0.9300
C15—C16	1.379 (6)	C33—C34	1.377 (7)
C15—H15	0.9300	C33—H33	0.9300
C16—H16	0.9300	C34—H34	0.9300
C17—C18	1.513 (5)	C35—C36	1.499 (5)
C17—H17	0.9800	C35—H35	0.9800
C18—H18A	0.9700	C36—H36A	0.9700
C18—H18B	0.9700	C36—H36B	0.9700
C8—O2—C9	115.9 (3)	C26—O6—C27	115.5 (3)
C17—O4—H4O	106 (3)	C35—O9—H9O	107 (5)
C18—O5—H5O	114 (4)	C36—O10—H10O	109 (3)
C10—N1—C2	124.6 (3)	C28—N2—C20	123.2 (3)
C10—N1—H1A	121 (2)	C28—N2—H2A	121 (2)
C2—N1—H1A	113 (2)	C20—N2—H2A	115 (2)
C6—C1—C2	109.0 (3)	C24—C19—C25	102.7 (4)
C6—C1—C7	99.2 (4)	C24—C19—C20	109.3 (3)
C2—C1—C7	101.5 (3)	C25—C19—C20	102.8 (4)
C6—C1—H1	115.1	C24—C19—H19	113.6
C2—C1—H1	115.1	C25—C19—H19	113.6
C7—C1—H1	115.1	C20—C19—H19	113.6
N1—C2—C8	109.5 (3)	N2—C20—C26	108.3 (3)
N1—C2—C1	114.8 (3)	N2—C20—C19	114.4 (3)
C8—C2—C1	111.4 (3)	C26—C20—C19	110.3 (3)
N1—C2—C3	110.3 (3)	N2—C20—C21	111.9 (3)
C8—C2—C3	108.2 (3)	C26—C20—C21	109.8 (3)
C1—C2—C3	102.4 (3)	C19—C20—C21	102.0 (3)
C17—C3—C4	119.8 (3)	C35—C21—C22	118.4 (4)
C17—C3—C2	117.6 (3)	C35—C21—C20	118.7 (3)
C4—C3—C2	102.8 (3)	C22—C21—C20	102.9 (3)
C17—C3—H3	105.1	C35—C21—H21	105.1
C4—C3—H3	105.1	C22—C21—H21	105.1
C2—C3—H3	105.1	C20—C21—H21	105.1
C5—C4—C7	101.4 (4)	C23—C22—C21	110.7 (4)
C5—C4—C3	111.9 (3)	C23—C22—C25	100.3 (5)
C7—C4—C3	100.3 (3)	C21—C22—C25	98.7 (4)
C5—C4—H4	113.9	C23—C22—H22	115.0
C7—C4—H4	113.9	C21—C22—H22	115.0
C3—C4—H4	113.9	C25—C22—H22	115.0
C4—C5—C6	103.3 (4)	C22—C23—C24	105.7 (5)
C4—C5—H5A	111.1	C22—C23—H23A	110.6
C6—C5—H5A	111.1	C24—C23—H23A	110.6
C4—C5—H5B	111.1	C22—C23—H23B	110.6
C6—C5—H5B	111.1	C24—C23—H23B	110.6
H5A—C5—H5B	109.1	H23A—C23—H23B	108.7
C1—C6—C5	105.1 (4)	C19—C24—C23	101.9 (5)
C1—C6—H6B	110.7	C19—C24—H24A	111.4
C5—C6—H6B	110.7	C23—C24—H24A	111.4
C1—C6—H6A	110.7	C19—C24—H24B	111.4
C5—C6—H6A	110.7	C23—C24—H24B	111.4
H6B—C6—H6A	108.8	H24A—C24—H24B	109.2
C4—C7—C1	94.2 (3)	C19—C25—C22	93.3 (3)
C4—C7—H7A	112.9	C19—C25—H25A	113.0
C1—C7—H7A	112.9	C22—C25—H25A	113.0
C4—C7—H7B	112.9	C19—C25—H25B	113.0
C1—C7—H7B	112.9	C22—C25—H25B	113.0
H7A—C7—H7B	110.3	H25A—C25—H25B	110.4
O1—C8—O2	123.5 (4)	O7—C26—O6	122.3 (4)
O1—C8—C2	124.4 (4)	O7—C26—C20	124.5 (4)
O2—C8—C2	112.0 (3)	O6—C26—C20	113.1 (3)
O2—C9—H9A	109.5	O6—C27—H27A	109.5
O2—C9—H9B	109.5	O6—C27—H27B	109.5
H9A—C9—H9B	109.5	H27A—C27—H27B	109.5
O2—C9—H9C	109.5	O6—C27—H27C	109.5
H9A—C9—H9C	109.5	H27A—C27—H27C	109.5
H9B—C9—H9C	109.5	H27B—C27—H27C	109.5
O3—C10—N1	121.2 (3)	O8—C28—N2	121.1 (4)
O3—C10—C11	121.0 (3)	O8—C28—C29	122.2 (4)
N1—C10—C11	117.6 (3)	N2—C28—C29	116.7 (3)
C12—C11—C16	117.4 (4)	C30—C29—C34	117.9 (4)
C12—C11—C10	123.9 (3)	C30—C29—C28	123.0 (4)
C16—C11—C10	118.7 (4)	C34—C29—C28	119.1 (4)
C11—C12—C13	121.6 (4)	C29—C30—C31	120.8 (4)
C11—C12—H12	119.2	C29—C30—H30	119.6
C13—C12—H12	119.2	C31—C30—H30	119.6
C12—C13—C14	119.6 (5)	C32—C31—C30	120.6 (4)
C12—C13—H13	120.2	C32—C31—H31	119.7
C14—C13—H13	120.2	C30—C31—H31	119.7
C15—C14—C13	119.9 (4)	C31—C32—C33	119.0 (4)
C15—C14—H14	120.0	C31—C32—H32	120.5
C13—C14—H14	120.0	C33—C32—H32	120.5
C14—C15—C16	120.2 (5)	C32—C33—C34	121.1 (5)
C14—C15—H15	119.9	C32—C33—H33	119.5
C16—C15—H15	119.9	C34—C33—H33	119.5
C15—C16—C11	121.1 (5)	C33—C34—C29	120.6 (4)
C15—C16—H16	119.4	C33—C34—H34	119.7
C11—C16—H16	119.4	C29—C34—H34	119.7
O4—C17—C18	110.9 (3)	O9—C35—C36	109.8 (3)
O4—C17—C3	111.1 (3)	O9—C35—C21	111.4 (3)
C18—C17—C3	111.5 (3)	C36—C35—C21	111.6 (3)
O4—C17—H17	107.7	O9—C35—H35	107.9
C18—C17—H17	107.7	C36—C35—H35	107.9
C3—C17—H17	107.7	C21—C35—H35	107.9
O5—C18—C17	108.3 (3)	O10—C36—C35	108.9 (3)
O5—C18—H18A	110.0	O10—C36—H36A	109.9
C17—C18—H18A	110.0	C35—C36—H36A	109.9
O5—C18—H18B	110.0	O10—C36—H36B	109.9
C17—C18—H18B	110.0	C35—C36—H36B	109.9
H18A—C18—H18B	108.4	H36A—C36—H36B	108.3
C10—N1—C2—C8	−52.3 (5)	C28—N2—C20—C26	−52.4 (5)
C10—N1—C2—C1	73.7 (4)	C28—N2—C20—C19	71.0 (5)
C10—N1—C2—C3	−171.3 (3)	C28—N2—C20—C21	−173.6 (4)
C6—C1—C2—N1	47.4 (5)	C24—C19—C20—N2	44.5 (5)
C7—C1—C2—N1	151.5 (3)	C25—C19—C20—N2	153.2 (3)
C6—C1—C2—C8	172.5 (4)	C24—C19—C20—C26	166.9 (4)
C7—C1—C2—C8	−83.4 (4)	C25—C19—C20—C26	−84.4 (4)
C6—C1—C2—C3	−72.0 (4)	C24—C19—C20—C21	−76.4 (5)
C7—C1—C2—C3	32.0 (4)	C25—C19—C20—C21	32.2 (4)
N1—C2—C3—C17	15.8 (4)	N2—C20—C21—C35	16.9 (5)
C8—C2—C3—C17	−103.9 (3)	C26—C20—C21—C35	−103.5 (4)
C1—C2—C3—C17	138.4 (3)	C19—C20—C21—C35	139.5 (4)
N1—C2—C3—C4	−118.1 (3)	N2—C20—C21—C22	−116.2 (4)
C8—C2—C3—C4	122.2 (3)	C26—C20—C21—C22	123.5 (4)
C1—C2—C3—C4	4.5 (3)	C19—C20—C21—C22	6.5 (4)
C17—C3—C4—C5	−65.9 (5)	C35—C21—C22—C23	−69.8 (6)
C2—C3—C4—C5	66.7 (4)	C20—C21—C22—C23	63.3 (5)
C17—C3—C4—C7	−172.7 (3)	C35—C21—C22—C25	−174.4 (4)
C2—C3—C4—C7	−40.1 (4)	C20—C21—C22—C25	−41.2 (5)
C7—C4—C5—C6	35.3 (4)	C21—C22—C23—C24	−71.2 (5)
C3—C4—C5—C6	−70.8 (4)	C25—C22—C23—C24	32.3 (4)
C2—C1—C6—C5	69.9 (4)	C25—C19—C24—C23	−38.5 (4)
C7—C1—C6—C5	−35.7 (4)	C20—C19—C24—C23	70.2 (5)
C4—C5—C6—C1	0.8 (4)	C22—C23—C24—C19	2.6 (5)
C5—C4—C7—C1	−56.1 (4)	C24—C19—C25—C22	56.8 (4)
C3—C4—C7—C1	58.9 (4)	C20—C19—C25—C22	−56.7 (4)
C6—C1—C7—C4	55.5 (4)	C23—C22—C25—C19	−53.3 (4)
C2—C1—C7—C4	−56.2 (4)	C21—C22—C25—C19	59.7 (4)
C9—O2—C8—O1	2.5 (6)	C27—O6—C26—O7	−3.4 (6)
C9—O2—C8—C2	−173.5 (4)	C27—O6—C26—C20	179.8 (4)
N1—C2—C8—O1	136.9 (4)	N2—C20—C26—O7	140.6 (5)
C1—C2—C8—O1	8.9 (6)	C19—C20—C26—O7	14.7 (6)
C3—C2—C8—O1	−102.9 (5)	C21—C20—C26—O7	−97.0 (5)
N1—C2—C8—O2	−47.1 (4)	N2—C20—C26—O6	−42.7 (4)
C1—C2—C8—O2	−175.1 (3)	C19—C20—C26—O6	−168.5 (4)
C3—C2—C8—O2	73.1 (4)	C21—C20—C26—O6	79.8 (4)
C2—N1—C10—O3	1.6 (5)	C20—N2—C28—O8	−2.7 (6)
C2—N1—C10—C11	177.3 (3)	C20—N2—C28—C29	176.1 (3)
O3—C10—C11—C12	−176.6 (4)	O8—C28—C29—C30	150.1 (4)
N1—C10—C11—C12	7.7 (5)	N2—C28—C29—C30	−28.6 (5)
O3—C10—C11—C16	3.6 (5)	O8—C28—C29—C34	−30.5 (6)
N1—C10—C11—C16	−172.1 (3)	N2—C28—C29—C34	150.7 (4)
C16—C11—C12—C13	3.0 (7)	C34—C29—C30—C31	−1.0 (6)
C10—C11—C12—C13	−176.7 (4)	C28—C29—C30—C31	178.4 (4)
C11—C12—C13—C14	0.1 (8)	C29—C30—C31—C32	0.0 (7)
C12—C13—C14—C15	−3.1 (8)	C30—C31—C32—C33	0.6 (7)
C13—C14—C15—C16	2.7 (8)	C31—C32—C33—C34	−0.3 (8)
C14—C15—C16—C11	0.6 (8)	C32—C33—C34—C29	−0.7 (8)
C12—C11—C16—C15	−3.4 (6)	C30—C29—C34—C33	1.3 (6)
C10—C11—C16—C15	176.3 (4)	C28—C29—C34—C33	−178.1 (4)
C4—C3—C17—O4	63.9 (4)	C22—C21—C35—O9	69.4 (5)
C2—C3—C17—O4	−62.0 (4)	C20—C21—C35—O9	−56.4 (5)
C4—C3—C17—C18	−60.3 (5)	C22—C21—C35—C36	−53.8 (5)
C2—C3—C17—C18	173.8 (3)	C20—C21—C35—C36	−179.6 (4)
O4—C17—C18—O5	65.6 (4)	O9—C35—C36—O10	67.1 (4)
C3—C17—C18—O5	−170.0 (3)	C21—C35—C36—O10	−168.8 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O4—H4O···O10	0.81 (4)	1.96 (4)	2.714 (4)	155 (4)
O5—H5O···O3^i	0.81 (6)	1.96 (6)	2.739 (4)	161 (5)
N1—H1A···O4	0.85 (3)	1.97 (4)	2.712 (4)	146 (3)
O9—H9O···O5	0.92 (6)	1.94 (6)	2.783 (4)	153 (5)
O10—H10O···O8^ii	0.86 (4)	1.86 (4)	2.673 (4)	159 (4)
N2—H2A···O9	0.82 (3)	1.98 (3)	2.698 (4)	146 (3)
O4—H4O···O5	0.81 (4)	2.49 (4)	2.857 (4)	109 (3)
O9—H9O···O10	0.92 (6)	2.48 (6)	2.874 (4)	106 (5)
C5—H5B···O4	0.97	2.30	3.005 (5)	129
C7—H7A···O1	0.97	2.62	3.140 (6)	114
C12—H12···O4	0.93	2.83	3.701 (5)	157
C4—H4···O7^iii	0.98	2.52	3.121 (5)	119
C5—H5A···O7^iii	0.97	2.65	3.298 (6)	125
C15—H15···O8^iv	0.93	2.82	3.711 (6)	161
C23—H23B···O9	0.97	2.35	3.067 (6)	131
C25—H25B···O7	0.97	2.58	3.107 (6)	114
C33—H33···O3^v	0.93	2.44	3.230 (6)	143

Symmetry codes: (i) −x+1, y+1/2, −z; (ii) x−1, y, z; (iii) x−1, y, z−1; (iv) −x+2, y−1/2, −z+1; (v) −x+2, y+1/2, −z.

(endoI) methyl (1R,2S,3R,4S)-2-benzamido-3-(1,2-dihydroxyethyl)bicyclo[2.2.1]heptane-2- carboxylate

Crystal data

C18H23NO5	Dx = 1.298 Mg m^−3
Mr = 333.37	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P212121	Cell parameters from 28 reflections
a = 7.187 (5) Å	θ = 7.6–12.5°
b = 11.720 (5) Å	µ = 0.10 mm^−1
c = 20.258 (5) Å	T = 293 K
V = 1706.4 (15) Å^3	Prism, colourless
Z = 4	0.40 × 0.36 × 0.30 mm
F(000) = 712

Data collection

Siemens P4 diffractometer	θmax = 25.0°, θmin = 2.0°
ω/2θ scans	h = −8→8
3472 measured reflections	k = −13→13
1748 independent reflections	l = −24→24
1525 reflections with I > 2σ(I)	3 standard reflections every 97 reflections
Rint = 0.013	intensity decay: none

Refinement

Refinement on F^2	H atoms treated by a mixture of independent and constrained refinement
Least-squares matrix: full	w = 1/[σ^2(Fo^2) + (0.031P)^2 + 0.3022P] where P = (Fo^2 + 2Fc^2)/3
R[F^2 > 2σ(F^2)] = 0.029	(Δ/σ)max < 0.001
wR(F^2) = 0.070	Δρmax = 0.16 e Å^−3
S = 1.06	Δρmin = −0.11 e Å^−3
1748 reflections	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
231 parameters	Extinction coefficient: 0.054 (2)

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	−0.4223 (2)	0.79237 (16)	0.88666 (9)	0.0566 (5)
O2	−0.2728 (2)	0.66717 (12)	0.82224 (8)	0.0491 (4)
O3	−0.3937 (2)	0.84340 (16)	0.73155 (8)	0.0504 (4)
O4	0.0100 (3)	1.08672 (15)	0.78474 (9)	0.0553 (5)
H4O	0.000 (5)	1.143 (3)	0.7567 (15)	0.074 (9)*
O5	−0.2572 (3)	1.25889 (15)	0.78843 (10)	0.0526 (5)
H5O	−0.359 (4)	1.282 (3)	0.7807 (14)	0.063 (9)*
N	−0.0940 (3)	0.84494 (17)	0.76384 (9)	0.0345 (4)
H	0.020 (4)	0.850 (2)	0.7516 (12)	0.048 (7)*
C1	0.0446 (3)	0.8040 (2)	0.87218 (12)	0.0438 (6)
H1	0.1071	0.7391	0.8513	0.053*
C2	−0.1312 (3)	0.84683 (18)	0.83492 (10)	0.0345 (5)
C3	−0.1556 (3)	0.97147 (18)	0.86306 (10)	0.0364 (5)
H3	−0.2697	0.9731	0.8895	0.044*
C4	0.0109 (4)	0.9823 (2)	0.91031 (12)	0.0503 (6)
H4	0.0472	1.0611	0.9202	0.060*
C5	−0.0270 (5)	0.9086 (2)	0.97168 (12)	0.0618 (8)
H5A	−0.1519	0.9211	0.9884	0.074*
H5B	0.0619	0.9248	1.0065	0.074*
C6	−0.0038 (4)	0.7858 (2)	0.94560 (12)	0.0544 (7)
H6A	−0.1181	0.7426	0.9505	0.065*
H6B	0.0957	0.7464	0.9685	0.065*
C7	0.1613 (3)	0.9121 (2)	0.87566 (14)	0.0540 (7)
H7A	0.1932	0.9419	0.8324	0.065*
H7B	0.2726	0.9029	0.9022	0.065*
C8	−0.2964 (3)	0.76988 (19)	0.85022 (11)	0.0396 (5)
C9	−0.4266 (4)	0.5888 (2)	0.82789 (15)	0.0659 (8)
H9A	−0.4352	0.5619	0.8726	0.099*
H9B	−0.4071	0.5253	0.7988	0.099*
H9C	−0.5399	0.6270	0.8161	0.099*
C10	−0.2261 (3)	0.84975 (19)	0.71729 (11)	0.0377 (5)
C11	−0.1621 (3)	0.86560 (19)	0.64807 (11)	0.0400 (5)
C12	−0.0215 (4)	0.9407 (2)	0.63307 (12)	0.0534 (7)
H12	0.0382	0.9805	0.6666	0.064*
C13	0.0316 (5)	0.9570 (2)	0.56801 (13)	0.0644 (8)
H13	0.1257	1.0086	0.5580	0.077*
C14	−0.0534 (5)	0.8978 (3)	0.51866 (13)	0.0671 (8)
H14	−0.0167	0.9085	0.4751	0.081*
C15	−0.1921 (5)	0.8230 (3)	0.53323 (14)	0.0770 (10)
H15	−0.2492	0.7820	0.4996	0.092*
C16	−0.2484 (4)	0.8077 (3)	0.59764 (13)	0.0648 (8)
H16	−0.3455	0.7578	0.6071	0.078*
C17	−0.1692 (3)	1.06546 (19)	0.81111 (11)	0.0387 (5)
H17	−0.2497	1.0385	0.7753	0.046*
C18	−0.2513 (4)	1.17388 (18)	0.83864 (13)	0.0489 (6)
H18A	−0.3760	1.1592	0.8548	0.059*
H18B	−0.1762	1.2006	0.8753	0.059*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0474 (10)	0.0585 (11)	0.0638 (11)	−0.0028 (9)	0.0193 (9)	0.0009 (9)
O2	0.0479 (10)	0.0376 (8)	0.0618 (10)	−0.0042 (8)	0.0006 (9)	−0.0017 (8)
O3	0.0325 (8)	0.0664 (11)	0.0525 (10)	−0.0016 (9)	−0.0039 (8)	−0.0020 (9)
O4	0.0560 (11)	0.0452 (10)	0.0649 (11)	0.0055 (9)	0.0220 (10)	0.0113 (9)
O5	0.0358 (9)	0.0488 (10)	0.0733 (12)	0.0085 (8)	0.0033 (9)	0.0182 (9)
N	0.0269 (10)	0.0401 (10)	0.0364 (10)	0.0008 (9)	0.0004 (8)	−0.0024 (8)
C1	0.0375 (12)	0.0438 (13)	0.0500 (14)	0.0104 (11)	−0.0072 (11)	0.0004 (11)
C2	0.0326 (11)	0.0369 (11)	0.0340 (11)	0.0051 (10)	−0.0008 (10)	−0.0008 (10)
C3	0.0361 (12)	0.0367 (12)	0.0364 (12)	0.0011 (10)	0.0022 (10)	−0.0008 (9)
C4	0.0571 (16)	0.0452 (13)	0.0486 (13)	−0.0019 (13)	−0.0148 (13)	−0.0045 (11)
C5	0.080 (2)	0.0651 (16)	0.0406 (13)	0.0112 (17)	−0.0131 (15)	−0.0023 (13)
C6	0.0636 (16)	0.0559 (14)	0.0436 (13)	0.0099 (15)	−0.0134 (13)	0.0082 (12)
C7	0.0360 (12)	0.0653 (16)	0.0608 (16)	0.0011 (13)	−0.0153 (13)	0.0013 (14)
C8	0.0390 (13)	0.0405 (12)	0.0392 (12)	0.0017 (11)	−0.0019 (11)	0.0053 (10)
C9	0.0648 (18)	0.0520 (15)	0.081 (2)	−0.0207 (16)	−0.0128 (16)	0.0063 (15)
C10	0.0345 (12)	0.0359 (11)	0.0427 (13)	−0.0021 (10)	−0.0026 (10)	−0.0020 (10)
C11	0.0415 (12)	0.0379 (12)	0.0407 (12)	0.0020 (11)	−0.0069 (11)	0.0006 (10)
C12	0.0615 (16)	0.0525 (14)	0.0461 (14)	−0.0108 (14)	0.0016 (13)	−0.0013 (11)
C13	0.075 (2)	0.0635 (17)	0.0544 (16)	−0.0129 (17)	0.0096 (16)	0.0099 (14)
C14	0.085 (2)	0.0762 (19)	0.0399 (15)	0.0061 (19)	0.0014 (16)	0.0081 (14)
C15	0.090 (2)	0.100 (2)	0.0408 (15)	−0.020 (2)	−0.0126 (17)	−0.0068 (15)
C16	0.0669 (17)	0.0782 (19)	0.0492 (15)	−0.0232 (17)	−0.0074 (15)	−0.0032 (14)
C17	0.0366 (11)	0.0403 (12)	0.0392 (12)	0.0000 (10)	0.0001 (10)	−0.0013 (10)
C18	0.0487 (14)	0.0438 (12)	0.0542 (14)	0.0059 (12)	0.0097 (13)	0.0071 (11)

Geometric parameters (Å, º)

O1—C8	1.197 (3)	C5—H5B	0.9700
O2—C8	1.341 (3)	C6—H6A	0.9700
O2—C9	1.442 (3)	C6—H6B	0.9700
O3—C10	1.241 (3)	C7—H7A	0.9700
O4—C17	1.416 (3)	C7—H7B	0.9700
O4—H4O	0.87 (3)	C9—H9A	0.9600
O5—C18	1.424 (3)	C9—H9B	0.9600
O5—H5O	0.80 (3)	C9—H9C	0.9600
N—C10	1.340 (3)	C10—C11	1.488 (3)
N—C2	1.465 (3)	C11—C12	1.374 (3)
N—H	0.86 (3)	C11—C16	1.375 (3)
C1—C7	1.521 (4)	C12—C13	1.385 (4)
C1—C6	1.542 (4)	C12—H12	0.9300
C1—C2	1.555 (3)	C13—C14	1.361 (4)
C1—H1	0.9800	C13—H13	0.9300
C2—C8	1.523 (3)	C14—C15	1.360 (4)
C2—C3	1.578 (3)	C14—H14	0.9300
C3—C17	1.527 (3)	C15—C16	1.378 (4)
C3—C4	1.538 (3)	C15—H15	0.9300
C3—H3	0.9800	C16—H16	0.9300
C4—C7	1.529 (4)	C17—C18	1.508 (3)
C4—C5	1.538 (4)	C17—H17	0.9800
C4—H4	0.9800	C18—H18A	0.9700
C5—C6	1.542 (4)	C18—H18B	0.9700
C5—H5A	0.9700
C8—O2—C9	116.2 (2)	C1—C7—H7B	112.8
C17—O4—H4O	108 (2)	C4—C7—H7B	112.8
C18—O5—H5O	114 (2)	H7A—C7—H7B	110.3
C10—N—C2	124.19 (19)	O1—C8—O2	123.6 (2)
C10—N—H	118.1 (17)	O1—C8—C2	125.8 (2)
C2—N—H	117.2 (17)	O2—C8—C2	110.29 (19)
C7—C1—C6	101.2 (2)	O2—C9—H9A	109.5
C7—C1—C2	101.65 (18)	O2—C9—H9B	109.5
C6—C1—C2	109.2 (2)	H9A—C9—H9B	109.5
C7—C1—H1	114.4	O2—C9—H9C	109.5
C6—C1—H1	114.4	H9A—C9—H9C	109.5
C2—C1—H1	114.4	H9B—C9—H9C	109.5
N—C2—C8	109.48 (17)	O3—C10—N	121.5 (2)
N—C2—C1	108.91 (18)	O3—C10—C11	121.8 (2)
C8—C2—C1	110.10 (17)	N—C10—C11	116.71 (19)
N—C2—C3	112.92 (18)	C12—C11—C16	118.9 (2)
C8—C2—C3	112.82 (18)	C12—C11—C10	121.1 (2)
C1—C2—C3	102.34 (18)	C16—C11—C10	120.0 (2)
C17—C3—C4	114.78 (19)	C11—C12—C13	120.1 (2)
C17—C3—C2	115.21 (18)	C11—C12—H12	120.0
C4—C3—C2	102.40 (17)	C13—C12—H12	120.0
C17—C3—H3	108.0	C14—C13—C12	120.3 (3)
C4—C3—H3	108.0	C14—C13—H13	119.9
C2—C3—H3	108.0	C12—C13—H13	119.9
C7—C4—C3	102.71 (18)	C15—C14—C13	119.9 (3)
C7—C4—C5	101.2 (2)	C15—C14—H14	120.1
C3—C4—C5	108.6 (2)	C13—C14—H14	120.1
C7—C4—H4	114.3	C14—C15—C16	120.3 (3)
C3—C4—H4	114.3	C14—C15—H15	119.8
C5—C4—H4	114.3	C16—C15—H15	119.8
C4—C5—C6	103.2 (2)	C11—C16—C15	120.5 (3)
C4—C5—H5A	111.1	C11—C16—H16	119.8
C6—C5—H5A	111.1	C15—C16—H16	119.8
C4—C5—H5B	111.1	O4—C17—C18	110.30 (19)
C6—C5—H5B	111.1	O4—C17—C3	109.21 (18)
H5A—C5—H5B	109.1	C18—C17—C3	112.21 (19)
C5—C6—C1	103.1 (2)	O4—C17—H17	108.3
C5—C6—H6A	111.2	C18—C17—H17	108.3
C1—C6—H6A	111.2	C3—C17—H17	108.3
C5—C6—H6B	111.2	O5—C18—C17	109.7 (2)
C1—C6—H6B	111.2	O5—C18—H18A	109.7
H6A—C6—H6B	109.1	C17—C18—H18A	109.7
C1—C7—C4	94.5 (2)	O5—C18—H18B	109.7
C1—C7—H7A	112.8	C17—C18—H18B	109.7
C4—C7—H7A	112.8	H18A—C18—H18B	108.2
C10—N—C2—C8	42.8 (3)	C9—O2—C8—O1	11.4 (3)
C10—N—C2—C1	163.2 (2)	C9—O2—C8—C2	−174.77 (19)
C10—N—C2—C3	−83.8 (3)	N—C2—C8—O1	−136.3 (2)
C7—C1—C2—N	83.3 (2)	C1—C2—C8—O1	104.0 (3)
C6—C1—C2—N	−170.3 (2)	C3—C2—C8—O1	−9.6 (3)
C7—C1—C2—C8	−156.65 (19)	N—C2—C8—O2	50.1 (2)
C6—C1—C2—C8	−50.2 (2)	C1—C2—C8—O2	−69.6 (2)
C7—C1—C2—C3	−36.5 (2)	C3—C2—C8—O2	176.72 (18)
C6—C1—C2—C3	70.0 (2)	C2—N—C10—O3	−8.2 (4)
N—C2—C3—C17	9.8 (3)	C2—N—C10—C11	170.5 (2)
C8—C2—C3—C17	−115.0 (2)	O3—C10—C11—C12	137.0 (3)
C1—C2—C3—C17	126.7 (2)	N—C10—C11—C12	−41.7 (3)
N—C2—C3—C4	−115.51 (19)	O3—C10—C11—C16	−40.7 (4)
C8—C2—C3—C4	119.7 (2)	N—C10—C11—C16	140.6 (2)
C1—C2—C3—C4	1.4 (2)	C16—C11—C12—C13	−0.1 (4)
C17—C3—C4—C7	−91.6 (2)	C10—C11—C12—C13	−177.8 (3)
C2—C3—C4—C7	34.0 (2)	C11—C12—C13—C14	−0.9 (5)
C17—C3—C4—C5	161.8 (2)	C12—C13—C14—C15	0.6 (5)
C2—C3—C4—C5	−72.6 (2)	C13—C14—C15—C16	0.7 (5)
C7—C4—C5—C6	−35.3 (3)	C12—C11—C16—C15	1.3 (4)
C3—C4—C5—C6	72.4 (3)	C10—C11—C16—C15	179.0 (3)
C4—C5—C6—C1	0.0 (3)	C14—C15—C16—C11	−1.6 (5)
C7—C1—C6—C5	35.5 (3)	C4—C3—C17—O4	43.2 (3)
C2—C1—C6—C5	−71.2 (3)	C2—C3—C17—O4	−75.4 (2)
C6—C1—C7—C4	−56.2 (2)	C4—C3—C17—C18	−79.5 (3)
C2—C1—C7—C4	56.3 (2)	C2—C3—C17—C18	161.9 (2)
C3—C4—C7—C1	−56.0 (2)	O4—C17—C18—O5	56.9 (3)
C5—C4—C7—C1	56.2 (2)	C3—C17—C18—O5	178.93 (19)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O4—H4O···N^i	0.87 (3)	2.50 (3)	3.239 (3)	143 (3)
O4—H4O···O2^i	0.87 (3)	2.55 (3)	3.026 (2)	116 (3)
O5—H5O···O3^ii	0.80 (3)	1.93 (3)	2.728 (3)	175 (3)
N—H···O5^iii	0.86 (3)	2.17 (3)	2.917 (3)	146 (2)
O4—H4O···O5	0.87 (3)	2.39 (3)	2.787 (3)	109 (2)
C3—H3···O1	0.98	2.39	2.882 (3)	111
C7—H7A···O4	0.97	2.36	2.960 (3)	120
C12—H12···O4	0.93	2.70	3.524 (3)	148
C12—H12···O2^i	0.93	2.77	3.513 (3)	138
C7—H7B···O1^iv	0.97	2.57	3.313 (4)	134
C9—H9B···O3^v	0.96	2.64	3.375 (3)	134

Symmetry codes: (i) −x, y+1/2, −z+3/2; (ii) −x−1, y+1/2, −z+3/2; (iii) −x, y−1/2, −z+3/2; (iv) x+1, y, z; (v) −x−1, y−1/2, −z+3/2.