2-C-Hydro­xymethyl-2,3-O-iso­propyl­idene-d-ribono-1,5-lactam

Newton, C.R.; Michela, I.S.; Fleet, G.W.J..; Blériot, Y.; Watkin, D.J.

doi:10.1107/S1600536804008141

organic compounds

CRYSTALLOGRAPHIC

COMMUNICATIONS

ISSN: 2056-9890

Volume 60| Part 5| May 2004| Pages o909-o910

https://doi.org/10.1107/S1600536804008141

ADDENDA AND ERRATA

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2-C-Hydroxymethyl-2,3-O-isopropylidene-D-ribono-1,5-lactam

Christopher R. Newton,^a ^* Iezzi Simone Michela,^b George W. J. Fleet,^b Yves Blériot ^c and David J. Watkin ^a

^aDepartment of Chemical Crystallography, Chemistry Research Laboratory, Oxford OX1 3TA, England, ^bDepartment of Organic Chemistry, Chemistry Research Laboratory, Oxford OX1 3TA, England, and ^cEcole Normale Supérieure, Département de Chimie, UMR 8642, 24 rue Lhomond, 75231 Paris Cedex 05, France

^*Correspondence e-mail: [email protected]

(Received 22 March 2004; accepted 5 April 2004; online 30 April 2004)

The title compound, C₉H₁₄NO₅, was formed by catalytic hydrogenation of an azidolactone using Pd-black in 1,4-dioxane.

Comment

The replacement of the ring O atom of a carbohydrate by nitrogen gives a range of sugar mimics (Winchester & Fleet, 1992 ), many of which are natural products widely spread in plants (Asano et al., 2000 ). Because of the multitude of potential biological activities, interest in understanding the structures in the search for transition-state analogues continues (Heck et al., 2004 ). Almost all of the natural products and their synthetic analogues contain straight carbon chains; however, there are some very promising indications that carbohydrate mimics with hydroxymethyl branches (Ichikawa & Igarashi, 1995 ; Ichikawa et al., 1998 ), as well as their deoxygenated equivalents (Lillelund et al., 2003 ; Ostrowski et al., 2003 ), will show significant inhibition of sugar-metabolizing enzymes. However, the chemistry of simple branched sugars as starting materials is little explored. The title compound, (3), is a powerful intermediate in which a stereochemical ambiguity arises from an aldol reaction; additionally, information about the conformation of both protected and unprotected lactams may help to understand the basis of their biological activity.

The azidolactol (1) was prepared from D-ribose and submitted to the key aldol branching step. Subsequent oxidation of the aldol product with bromine water gave the branched azidolactone (2). Hydrogenation of (2) resulted in initial reduction of the azide to the corresponding amine which underwent subsequent isomerization to the title lactam (3). The X-ray crystal structure of (3) removes any ambiguity about the course of the aldol condensation.

Figure 1

The molecular structure of (3), with 50% probability displacement ellipsoids.

Experimental

2-C-Hydroxymethyl-2,3-O-isopropylidene-D-ribono-1,5-lactam was obtained on reduction of 5-azido-2,3-O-isopropylidene-D-hamamelono-1,4-lactone, (2), using Pd-black and hydrogen gas in 1,4-dioxane at low reaction concentration (2.5 mg ml⁻¹). A quantitative yield of the title compound was obtained. The title material was then recrystallized using solvent evaporation (methanol), appearing as colourless block crystals.

Crystal data

C₉H₁₄NO₅
M_r = 216.21
Orthorhombic, P2₁2₁2₁
a = 7.3137 (1) Å
b = 10.6657 (2) Å
c = 12.6476 (3) Å
V = 986.59 (3) Å³
Z = 4
D_x = 1.456 Mg m⁻³
Mo Kα radiation
Cell parameters from 1329 reflections
θ = 5–27°
μ = 0.12 mm⁻¹
T = 150 K
Block, colourless
0.20 × 0.10 × 0.10 mm

Data collection

Nonius KappaCCD diffractometer
ω scans
Absorption correction: multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1997 ) T_min = 0.976, T_max = 0.988
2272 measured reflections
1315 independent reflections
1195 reflections with I > 2σ(I)
R_int = 0.01
θ_max = 27.5°
h = −9 → 9
k = −13 → 13
l = −16 → 16

Refinement

Refinement on F²
R[F² > 2σ(F²)] = 0.035
wR(F²) = 0.087
S = 0.98
1315 reflections
136 parameters
H-atom parameters constrained
w = 1/[σ²(F*) + (0.0403p)² + 0.549p] where p = 0.333max(F_o²,0) + 0.667F_c²
(Δ/σ)_max < 0.001
Δρ_max = 0.44 e Å⁻³
Δρ_min = −0.25 e Å⁻³

Table 1

Selected geometric parameters (Å, °)

C1—C14	1.528 (3)
C1—O11	1.428 (2)
C1—C6	1.531 (3)
C1—C2	1.521 (3)
C2—O9	1.432 (2)
C2—C3	1.513 (3)
C3—O8	1.431 (2)
C3—C4	1.517 (3)
C4—N5	1.473 (3)
N5—C6	1.331 (3)
C6—O7	1.259 (3)
O9—C10	1.438 (2)
C10—C13	1.513 (3)
C10—C12	1.512 (3)
C10—O11	1.444 (2)
C14—O15	1.419 (3)

C14—C1—O11	107.00 (17)
C14—C1—C6	110.38 (17)
O11—C1—C6	107.11 (16)
C14—C1—C2	114.23 (17)
O11—C1—C2	103.03 (16)
C6—C1—C2	114.30 (16)
O9—C2—C3	110.70 (16)
O9—C2—C1	102.89 (15)
C3—C2—C1	111.33 (17)
O8—C3—C4	109.83 (16)
O8—C3—C2	111.11 (16)
C4—C3—C2	109.97 (16)
N5—C4—C3	110.11 (16)
C6—N5—C4	125.82 (18)
O7—C6—N5	122.03 (19)
O7—C6—C1	118.13 (18)
N5—C6—C1	119.79 (18)
C10—O9—C2	108.04 (15)
C13—C10—C12	114.02 (19)
C13—C10—O11	107.24 (16)
C12—C10—O11	110.31 (17)
C13—C10—O9	111.49 (18)
C12—C10—O9	107.55 (17)
O11—C10—O9	105.94 (16)
C1—O11—C10	109.05 (14)
O15—C14—C1	109.28 (17)

H atoms were placed geometrically after each cycle, at a distance of 1.0 Å; U_iso values were set to 1.2 times the U_eq value of the parent atom. The absolute configuration was assumed to be the same as that of the sugar and the Friedel pairs were merged in the final refinement.

Data collection: COLLECT (Nonius, 1997–2001 ); cell refinement: DENZO/SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO/SCALEPACK; program(s) used to solve structure: SIR92 (Altomare et al., 1994 ); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003 ); molecular graphics: CAMERON (Watkin et al., 1996 ); software used to prepare material for publication: CRYSTALS.

Supporting information

Crystal structure: contains datablocks global, 3. DOI: https://doi.org/10.1107/S1600536804008141/na6312sup1.cif

Structure factors: contains datablock 3. DOI: https://doi.org/10.1107/S1600536804008141/na63123sup2.hkl

Computing details top

Data collection: COLLECT (Nonius, 1997); cell refinement: DENZO/SCALEPACK; data reduction: DENZO/SCALEPACK (Otwinowski & Minor, 1996); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003); molecular graphics: CAMERON (Watkin et al., 1996); software used to prepare material for publication: CRYSTALS.

2-C-Hydroxymethyl-2,3-O-isopropylidene-D-ribono-1,5-lactam top

Crystal data top

C₉H₁₄NO₅	D_x = 1.456 Mg m⁻³
M_r = 216.21	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P2₁2₁2₁	Cell parameters from 1329 reflections
a = 7.3137 (1) Å	θ = 5–27°
b = 10.6657 (2) Å	µ = 0.12 mm⁻¹
c = 12.6476 (3) Å	T = 150 K
V = 986.59 (3) Å³	Plate, colourless
Z = 4	0.20 × 0.10 × 0.10 mm
F(000) = 460

Data collection top

Nonius KappaCCD diffractometer	1195 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.01
ω scans	θ_max = 27.5°, θ_min = 5.2°
Absorption correction: multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1996)	h = −9→9
T_min = 0.976, T_max = 0.988	k = −13→13
2272 measured reflections	l = −16→16
1315 independent reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.035	H-atom parameters constrained
wR(F²) = 0.087	w = 1/[σ²(F*) + (0.0403p)² + 0.549p] where p = 0.333max(F_o²,0) + 0.667F_c²
S = 0.98	(Δ/σ)_max = 0.000238
1315 reflections	Δρ_max = 0.44 e Å⁻³
136 parameters	Δρ_min = −0.25 e Å⁻³
0 restraints

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C1	0.7866 (3)	0.0035 (2)	0.02895 (15)	0.0188
C2	0.7198 (3)	0.11166 (19)	−0.03931 (16)	0.0193
C3	0.6725 (3)	0.0679 (2)	−0.14980 (15)	0.0201
C4	0.5206 (3)	−0.0288 (2)	−0.14517 (16)	0.0229
N5	0.5697 (2)	−0.12992 (17)	−0.07111 (15)	0.0231
C6	0.6915 (3)	−0.1217 (2)	0.00682 (17)	0.0206
O7	0.7278 (2)	−0.21316 (13)	0.06611 (13)	0.0263
O8	0.6178 (2)	0.17082 (15)	−0.21510 (11)	0.0246
O9	0.5593 (2)	0.15309 (15)	0.01535 (11)	0.0233
C10	0.5842 (3)	0.1282 (2)	0.12615 (16)	0.0202
O11	0.7351 (2)	0.04121 (14)	0.13309 (11)	0.0213
C12	0.4107 (3)	0.0679 (2)	0.16656 (17)	0.0270
C13	0.6394 (3)	0.2453 (2)	0.18566 (19)	0.0292
C14	0.9941 (3)	−0.0134 (2)	0.02935 (16)	0.0218
O15	1.0513 (2)	−0.05872 (15)	−0.07082 (12)	0.0291
H21	0.8129	0.1802	−0.0492	0.0233*
H31	0.7838	0.0248	−0.1813	0.0262*
H41	0.4980	−0.0634	−0.2173	0.0283*
H42	0.4059	0.0146	−0.1199	0.0283*
H121	0.4229	0.0489	0.2435	0.0338*
H122	0.3890	−0.0127	0.1269	0.0338*
H123	0.3048	0.1253	0.1548	0.0338*
H131	0.6555	0.2262	0.2625	0.0368*
H132	0.7581	0.2780	0.1564	0.0368*
H133	0.5432	0.3116	0.1772	0.0368*
H141	1.0564	0.0687	0.0449	0.0264*
H142	1.0305	−0.0751	0.0866	0.0264*
H2	1.1000	−0.1353	−0.0668	0.0500*
H5	0.6767	0.1578	−0.2858	0.0500*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0176 (10)	0.0214 (9)	0.0176 (9)	−0.0002 (8)	0.0004 (8)	0.0006 (8)
C2	0.0184 (9)	0.0199 (9)	0.0194 (9)	0.0000 (8)	0.0014 (8)	−0.0007 (8)
C3	0.0200 (9)	0.0221 (10)	0.0182 (9)	0.0017 (8)	−0.0010 (8)	0.0019 (8)
C4	0.0229 (10)	0.0246 (11)	0.0213 (10)	−0.0012 (9)	−0.0052 (9)	0.0020 (8)
N5	0.0229 (8)	0.0226 (8)	0.0237 (8)	−0.0016 (8)	−0.0054 (8)	0.0017 (8)
C6	0.0189 (9)	0.0219 (9)	0.0209 (10)	0.0006 (8)	0.0004 (8)	0.0004 (8)
O7	0.0277 (8)	0.0214 (7)	0.0298 (8)	−0.0024 (7)	−0.0048 (7)	0.0043 (6)
O8	0.0267 (8)	0.0261 (8)	0.0209 (7)	0.0028 (7)	−0.0006 (6)	0.0043 (6)
O9	0.0232 (7)	0.0294 (8)	0.0172 (7)	0.0093 (7)	0.0018 (6)	0.0017 (6)
C10	0.0210 (10)	0.0226 (10)	0.0169 (9)	0.0027 (9)	−0.0016 (8)	0.0009 (8)
O11	0.0227 (7)	0.0248 (7)	0.0163 (6)	0.0055 (7)	−0.0009 (6)	−0.0005 (6)
C12	0.0222 (10)	0.0334 (12)	0.0254 (11)	0.0006 (10)	0.0011 (9)	0.0033 (10)
C13	0.0319 (12)	0.0249 (11)	0.0307 (11)	0.0028 (10)	−0.0048 (10)	−0.0046 (10)
C14	0.0180 (9)	0.0242 (10)	0.0231 (10)	0.0007 (9)	−0.0001 (9)	−0.0004 (9)
O15	0.0294 (8)	0.0325 (8)	0.0255 (8)	0.0114 (7)	0.0059 (7)	0.0040 (7)

Geometric parameters (Å, º) top

C1—C14	1.528 (3)	O8—H5	1.002
C1—O11	1.428 (2)	O9—C10	1.438 (2)
C1—C6	1.531 (3)	C10—C13	1.513 (3)
C1—C2	1.521 (3)	C10—C12	1.512 (3)
C2—H21	1.007	C10—O11	1.444 (2)
C2—O9	1.432 (2)	C12—H123	0.998
C2—C3	1.513 (3)	C12—H122	1.007
C3—H31	1.016	C12—H121	0.998
C3—O8	1.431 (2)	C13—H133	1.003
C3—C4	1.517 (3)	C13—H132	1.006
C4—H42	1.010	C13—H131	0.999
C4—H41	0.998	C14—H142	1.013
C4—N5	1.473 (3)	C14—H141	1.007
N5—C6	1.331 (3)	C14—O15	1.419 (3)
C6—O7	1.259 (3)	O15—H2	0.892

C14—C1—O11	107.00 (17)	H5—O8—C3	106.752
C14—C1—C6	110.38 (17)	C10—O9—C2	108.04 (15)
O11—C1—C6	107.11 (16)	C13—C10—C12	114.02 (19)
C14—C1—C2	114.23 (17)	C13—C10—O11	107.24 (16)
O11—C1—C2	103.03 (16)	C12—C10—O11	110.31 (17)
C6—C1—C2	114.30 (16)	C13—C10—O9	111.49 (18)
H21—C2—O9	112.952	C12—C10—O9	107.55 (17)
H21—C2—C3	105.327	O11—C10—O9	105.94 (16)
O9—C2—C3	110.70 (16)	C1—O11—C10	109.05 (14)
H21—C2—C1	113.805	H123—C12—H122	109.083
O9—C2—C1	102.89 (15)	H123—C12—H121	109.798
C3—C2—C1	111.33 (17)	H122—C12—H121	109.056
H31—C3—O8	110.168	H123—C12—C10	109.863
H31—C3—C4	107.155	H122—C12—C10	109.099
O8—C3—C4	109.83 (16)	H121—C12—C10	109.920
H31—C3—C2	108.516	H133—C13—H132	108.752
O8—C3—C2	111.11 (16)	H133—C13—H131	109.264
C4—C3—C2	109.97 (16)	H132—C13—H131	109.064
H42—C4—H41	108.764	H133—C13—C10	109.966
H42—C4—N5	109.677	H132—C13—C10	109.488
H41—C4—N5	110.531	H131—C13—C10	110.279
H42—C4—C3	107.994	H142—C14—H141	107.835
H41—C4—C3	109.712	H142—C14—O15	109.835
N5—C4—C3	110.11 (16)	H141—C14—O15	109.681
C6—N5—C4	125.82 (18)	H142—C14—C1	109.874
O7—C6—N5	122.03 (19)	H141—C14—C1	110.317
O7—C6—C1	118.13 (18)	O15—C14—C1	109.28 (17)
N5—C6—C1	119.79 (18)	H2—O15—C14	112.190

Acknowledgements

Financial support (to MIS), provided through the European Community's Human Potential Programme under contract HPRN-CT-2002-00173, is gratefully acknowledged.

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