(1R,5S,8R)-1,8-Di­hydroxy-6-oxa-3-aza­bi­cyclo­[3.2.1]­octan-2-one

Punzo, F.; Watkin, D.J.; Simone, M.I.; Fleet, G.W.J.

doi:10.1107/S1600536804028983

organic compounds

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ISSN: 2056-9890

Volume 60| Part 12| December 2004| Pages o2315-o2317

https://doi.org/10.1107/S1600536804028983

(1R,5S,8R)-1,8-Dihydroxy-6-oxa-3-azabicyclo[3.2.1]octan-2-one

Francesco Punzo,^a ^*‡ David J. Watkin,^b Michela Iezzi Simone ^c and George W. J. Fleet ^c

^aDipartimento di Scienze Chimiche, Facoltà di Farmacia, Università di Catania, Viale A. Doria 6, 95125 Catania, Italy, ^bDepartment of Chemical Crystallography, Chemical Research Laboratory, Mansfield Road, Oxford OX1 3TA, England, and ^cDepartment of Organic Chemistry, Chemical Research Laboratory, Mansfield Road, Oxford OX1 3TA, England
^*Correspondence e-mail: francesco.punzo@chemistry.oxford.ac.uk

(Received 4 November 2004; accepted 9 November 2004; online 13 November 2004)

The crystal structure of the title bicyclic lactam, C₆H₉NO₄, has firmly established the stereochemistry of the branched δ-sugar amino acid scaffold.

Comment

Sugar amino acids (SAA) have been extensively investigated as peptidomimetics (Chakraborty et al., 2004 ). δ-Tetrahydrofuran (THF) SAA have been shown to be dipeptide isosteres (Grotenberg et al., 2004 ; van Well et al., 2003 ); in particular, those THF SAA which have the carboxylic acid and amino methyl components cis to each other, as in (1) (see scheme), almost invariably induce β-turn-like structures in their homooligomers (Smith et al., 1998 , 2003 ).

Most such THF SAA have been derived from carbohydrates and all examples previously have contained a linear carbon chain. The branched THF SAA scaffold (2), prepared from a branched sugar lactone (Hotchkiss et al., 2004 ), spontaneously underwent an intramolecular cyclization to form the crystalline bicyclic lactam (3) (Figs. 1 and 2, and Table 1). A number of stereochemical and structural uncertainties in the synthesis of (2) are removed by the X-ray crystallographic analysis of (3).

Figure 1
The molecular structure of (3

), with displacement ellipsoids drawn at the 50% probability level. H-atom radii are arbitrary.

Figure 2
Packing diagram of (3

), viewed down the a axis.

Experimental

The bicyclic compound was dissolved in methanol in a flask and then crystallized as the solvent slowly evaporated to give colourless plate-like crystals. A suitable piece was cut from a larger crystal.

Crystal data

C₆H₉NO₄
M_r = 159.14
Orthorhombic, P2₁2₁2₁
a = 5.9624 (1) Å
b = 10.5889 (2) Å
c = 10.7089 (2) Å
V = 676.11 (2) Å³
Z = 4
D_x = 1.563 Mg m⁻³
Mo Kα radiation
Cell parameters from 1160 reflections
θ = 5–30°
μ = 0.13 mm⁻¹
T = 190 K
Block cut from plate, colourless
0.50 × 0.30 × 0.20 mm

Data collection

Nonius KappaCCD diffractometer
ω scans
Absorption correction: multi-scan DENZO/SCALEPACK (Otwinowski & Minor, 1997 ) T_min = 0.96, T_max = 0.97
1981 measured reflections
1158 independent reflections
1158 reflections with no I/σ(I) cutoff
R_int = 0.007
θ_max = 30.0°
h = −8 → 8
k = −14 → 14
l = −14 → 15

Refinement

Refinement on F²
R[F² > 2σ(F²)] = 0.028
wR(F²) = 0.069
S = 1.03
1158 reflections
119 parameters
H atoms treated by a mixture of independent and constrained refinement
w = 1/[σ²(F*) + 0.035p² + 0.136p] where p = [max(F_o²,0) + 2F_c²]/3
(Δ/σ)_max < 0.001
Δρ_max = 0.27 e Å⁻³
Δρ_min = −0.15 e Å⁻³
Extinction correction: Larson (1970 )
Extinction coefficient: 160 (40)

Table 1
Selected geometric parameters (Å, °)

C1—C2	1.5387 (17)
C1—C5	1.5292 (17)
C1—C8	1.5330 (16)
C1—O11	1.4028 (14)
C2—C3	1.5263 (18)
C2—O10	1.4080 (15)
C3—O4	1.4383 (17)
C3—C6	1.5125 (19)
O4—C5	1.4374 (16)
C6—N7	1.4651 (17)
N7—C8	1.3363 (16)
C8—O9	1.2348 (15)

C2—C1—C5	100.65 (10)
C2—C1—C8	107.94 (9)
C5—C1—C8	110.19 (10)
C2—C1—O11	115.93 (10)
C5—C1—O11	109.32 (9)
C8—C1—O11	112.17 (10)
C1—C2—C3	98.03 (9)
C1—C2—O10	114.20 (10)
C3—C2—O10	111.84 (10)
C2—C3—O4	103.70 (10)
C2—C3—C6	110.98 (10)
O4—C3—C6	109.68 (11)
C3—O4—C5	109.17 (10)
C1—C5—O4	105.12 (10)
C3—C6—N7	110.52 (10)
C6—N7—C8	125.51 (10)
C1—C8—N7	116.23 (10)
C1—C8—O9	121.38 (11)
N7—C8—O9	122.35 (11)

As the data were collected with molybdenum radiation, there were no measurable anomalous differences, as a consequence of which it was admissible to merge Friedel pairs of reflections. The H atoms were all seen in a difference map but those attached to carbon were placed geometrically. Their positions and U_iso were regularized using slack restraints. The refinement was completed using riding constraints for the H atoms bonded to carbon, and retaining the slack restraints for the other H atoms.

Data collection: COLLECT (Nonius, 1997 ); 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/S1600536804028983/tk6196sup1.cif

Structure factors: contains datablock 3. DOI: https://doi.org/10.1107/S1600536804028983/tk61963sup2.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.

(1R,5S,8R)-1,8-Dihydroxy-6-oxa-3-azabicyclo[3.2.1]octan-2-one top

Crystal data top

C₆H₉NO₄	F(000) = 336
M_r = 159.14	D_x = 1.563 Mg m⁻³
Orthorhombic, P2₁2₁2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 1160 reflections
a = 5.9624 (1) Å	θ = 5–30°
b = 10.5889 (2) Å	µ = 0.13 mm⁻¹
c = 10.7089 (2) Å	T = 190 K
V = 676.11 (2) Å³	Plate, colourless
Z = 4	0.50 × 0.30 × 0.20 mm

Data collection top

Nonius KappaCCD diffractometer	1158 reflections with no I/σ(I) cutoff
Graphite monochromator	R_int = 0.007
ω scans	θ_max = 30.0°, θ_min = 5.2°
Absorption correction: multi-scan DENZO/SCALEPACK (Otwinowski & Minor, 1996)	h = −8→8
T_min = 0.96, T_max = 0.97	k = −14→14
1981 measured reflections	l = −14→15
1158 independent reflections

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F² > 2σ(F²)] = 0.028	Method: SHELXL97 (Sheldrick, 1997); w = 1/[σ²(F*) + 0.035p² + 0.136p] where p = 0.333max(F_o²,0) + (1-0.333)/F_c²
wR(F²) = 0.069	(Δ/σ)_max < 0.001
S = 1.03	Δρ_max = 0.27 e Å⁻³
1158 reflections	Δρ_min = −0.15 e Å⁻³
119 parameters	Extinction correction: Larson (1970). Crystallographic Computing eq 22
22 restraints	Extinction coefficient: 160 (40)
Primary atom site location: structure-invariant direct methods

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

	x	y	z	U_iso*/U_eq
C1	0.46908 (19)	0.57839 (11)	0.38206 (11)	0.0155
C2	0.3993 (2)	0.53163 (12)	0.51244 (11)	0.0189
C3	0.1674 (2)	0.48138 (12)	0.47830 (12)	0.0222
O4	0.07521 (16)	0.57859 (10)	0.39976 (11)	0.0281
C5	0.2554 (2)	0.64695 (12)	0.34158 (13)	0.0214
C6	0.1851 (2)	0.35936 (13)	0.40555 (13)	0.0251
N7	0.35777 (19)	0.36957 (10)	0.30873 (10)	0.0225
C8	0.5087 (2)	0.46236 (11)	0.29935 (11)	0.0177
O9	0.66711 (17)	0.45784 (10)	0.22519 (9)	0.0280
O10	0.53826 (18)	0.43619 (9)	0.56141 (9)	0.0264
O11	0.65015 (14)	0.66291 (8)	0.37860 (9)	0.0214
H21	0.389 (2)	0.6029 (13)	0.5712 (13)	0.0227*
H31	0.068 (2)	0.4703 (14)	0.5491 (13)	0.0261*
H51	0.258 (3)	0.7354 (13)	0.3728 (13)	0.0251*
H52	0.237 (3)	0.6469 (13)	0.2507 (12)	0.0251*
H61	0.221 (3)	0.2901 (13)	0.4609 (14)	0.0304*
H62	0.039 (2)	0.3439 (15)	0.3661 (14)	0.0304*
H9	0.7732	0.6178	0.3838	0.0500*
H11	0.5929	0.4673	0.6253	0.0500*
H1	0.3644	0.3088	0.2554	0.0500*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0115 (4)	0.0152 (4)	0.0197 (5)	−0.0004 (4)	−0.0014 (4)	0.0014 (4)
C2	0.0194 (5)	0.0198 (5)	0.0177 (5)	0.0005 (5)	−0.0002 (4)	−0.0013 (4)
C3	0.0167 (5)	0.0264 (6)	0.0234 (5)	−0.0017 (5)	0.0041 (5)	0.0011 (5)
O4	0.0121 (4)	0.0292 (5)	0.0430 (6)	0.0011 (4)	0.0002 (4)	0.0057 (4)
C5	0.0134 (5)	0.0204 (5)	0.0305 (6)	0.0018 (5)	−0.0026 (5)	0.0033 (5)
C6	0.0210 (6)	0.0235 (6)	0.0308 (7)	−0.0081 (5)	0.0017 (5)	0.0002 (5)
N7	0.0228 (5)	0.0201 (5)	0.0245 (5)	−0.0026 (4)	0.0013 (5)	−0.0066 (4)
C8	0.0166 (5)	0.0205 (5)	0.0160 (5)	0.0019 (5)	−0.0015 (4)	0.0005 (4)
O9	0.0227 (4)	0.0349 (5)	0.0263 (4)	0.0006 (4)	0.0083 (4)	−0.0029 (4)
O10	0.0319 (5)	0.0240 (4)	0.0233 (4)	0.0012 (4)	−0.0098 (4)	0.0033 (4)
O11	0.0124 (4)	0.0167 (4)	0.0352 (5)	−0.0020 (3)	−0.0031 (4)	0.0042 (4)

Geometric parameters (Å, º) top

C1—C2	1.5387 (17)	C5—H51	0.994 (13)
C1—C5	1.5292 (17)	C5—H52	0.979 (13)
C1—C8	1.5330 (16)	C6—N7	1.4651 (17)
C1—O11	1.4028 (14)	C6—H61	0.967 (13)
C2—C3	1.5263 (18)	C6—H62	0.979 (14)
C2—O10	1.4080 (15)	N7—C8	1.3363 (16)
C2—H21	0.985 (13)	N7—H1	0.861
C3—O4	1.4383 (17)	C8—O9	1.2348 (15)
C3—C6	1.5125 (19)	O10—H11	0.826
C3—H31	0.969 (13)	O11—H9	0.877
O4—C5	1.4374 (16)

C2—C1—C5	100.65 (10)	C1—C5—H51	109.7 (9)
C2—C1—C8	107.94 (9)	O4—C5—H51	109.9 (9)
C5—C1—C8	110.19 (10)	C1—C5—H52	111.9 (9)
C2—C1—O11	115.93 (10)	O4—C5—H52	110.4 (9)
C5—C1—O11	109.32 (9)	H51—C5—H52	109.7 (11)
C8—C1—O11	112.17 (10)	C3—C6—N7	110.52 (10)
C1—C2—C3	98.03 (9)	C3—C6—H61	110.3 (9)
C1—C2—O10	114.20 (10)	N7—C6—H61	109.6 (9)
C3—C2—O10	111.84 (10)	C3—C6—H62	107.6 (9)
C1—C2—H21	110.5 (8)	N7—C6—H62	109.3 (9)
C3—C2—H21	111.3 (9)	H61—C6—H62	109.5 (12)
O10—C2—H21	110.4 (8)	C6—N7—C8	125.51 (10)
C2—C3—O4	103.70 (10)	C6—N7—H1	116.531
C2—C3—C6	110.98 (10)	C8—N7—H1	117.916
O4—C3—C6	109.68 (11)	C1—C8—N7	116.23 (10)
C2—C3—H31	114.0 (9)	C1—C8—O9	121.38 (11)
O4—C3—H31	108.2 (9)	N7—C8—O9	122.35 (11)
C6—C3—H31	110.0 (9)	C2—O10—H11	104.724
C3—O4—C5	109.17 (10)	C1—O11—H9	107.130
C1—C5—O4	105.12 (10)

Footnotes

‡Current address: Visiting Scientist at the Department of Chemical, Crystallography, Chemical Research Laboratory, Mansfield Road, Oxford OX1 3TA, England

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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