(2S,3R,4R,5R)-3,4-Dihydr­oxy-5-(hydroxy­meth­yl)pyrrolidine-2-carboxylic acid [(2S,3R,4R,5R)-3,4-dihydr­oxy-5-(hydroxy­meth­yl)proline]

Abstract

The crystal structure of the title compound, C₆H₁₁NO₅, establishes the relative configuration at the four stereogenic centres; the absolute configuration is determined by the use of d-glucuronolactone as the starting material for the synthesis. Mol­ecules are linked by inter­molecular O—H⋯O and N—H⋯O hydrogen bonds into a three-dimensional network, with each mol­ecule acting as a donor and acceptor for five hydrogen bonds.

Related literature

For related literature on imino­sugars, see: Asano et al. (2000 ▶); Watson et al. (2001 ▶). For related literature on pipecolic acids, see: Fleet et al. (1987 ▶); Booth et al. (2007 ▶); Bashyal, Chow, Fellows & Fleet (1987 ▶); Manning et al. (1985 ▶); di Bello et al. (1984 ▶); Yoshimura et al. (2008 ▶). For related literature on bulgecinine, see: Toumi et al. (2008 ▶); Bashyal et al. (1986 ▶); Bashyal, Chow & Fleet (1987 ▶); Shinagawa et al. (1984 ▶, 1985 ▶). For related literature on alexines, see: Pereira et al. (1991 ▶); Donohoe et al. (2008 ▶); Kato et al. (2003 ▶); Wormald et al. (1998 ▶). For absolute configuration, see: Flack (1983 ▶); Flack & Bernardinelli (2000 ▶); Flack & Shmueli (2007 ▶); Hooft et al. (2008 ▶); Thompson et al. (2008 ▶); Watkin (1994 ▶). For the weighting scheme, see: Prince (1982 ▶); Thompson & Watkin (2009 ▶).

Experimental

Crystal data

• C₆H₁₁NO₅

• M _r = 177.16

• Triclinic,

• a = 5.4160 (2) Å

• b = 5.8236 (3) Å

• c = 6.6006 (3) Å

• α = 102.836 (2)°

• β = 104.776 (2)°

• γ = 102.8244 (19)°

• V = 187.50 (2) ų

• Z = 1

• Mo Kα radiation

• μ = 0.14 mm⁻¹

• T = 150 K

• 0.25 × 0.17 × 0.06 mm

Data collection

• Area diffractometer

• Absorption correction: multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1997 ▶) T _min = 0.94, T _max = 0.99

• 2314 measured reflections

• 834 independent reflections

• 814 reflections with I > 2σ(I)

• R _int = 0.025

Refinement

• R[F ² > 2σ(F ²)] = 0.027

• wR(F ²) = 0.066

• S = 1.00

• 834 reflections

• 109 parameters

• 3 restraints

• H-atom parameters constrained

• Δρ_max = 0.24 e Å⁻³

• Δρ_min = −0.17 e Å⁻³

Data collection: COLLECT (Nonius, 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.

Supplementary Material

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O8—H81⋯O1i	0.83	1.85	2.679 (3)	175
N5—H51⋯O11ii	0.88	2.03	2.873 (3)	160
N5—H52⋯O3iii	0.89	1.93	2.814 (3)	173
O11—H111⋯O1iii	0.82	1.89	2.696 (3)	170
O12—H121⋯O8iv	0.82	1.91	2.668 (3)	154

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) .

supplementary crystallographic information

Comment

This paper firmly establishes the structure of the trihydroxyproline 1 (Fig. 1), the amino acid corresponding to DMDP 2. There are over 100 iminosugars that have been isolated as natural products [such as DMDP 2 and DNJ 4] that are the equivalent of carbohydrates with the ring oxygen replaced by nitrogen (Asano et al., 2000; Watson et al., 2001). In contrast, the pipecolic acid BR1 3 [related to DNJ 4 in the same way as 1 to 2] (Fleet et al.,1987; Booth et al., 2007; Bashyal, Chow, Fellows & Fleet, 1987) is among the rare examples of naturally occurring amino acid sugar analogues. BR1 3 was isolated from the seeds of Baphia racemosa (Manning et al., 1985) and is an inhibitor of glucuronidase and iduronidase (di Bello et al., 1984; Yoshimura et al., 2008). Bulgecinine 5 (Toumi et al., 2008; Bashyal et al., 1986; Bashyal, Chow & Fleet, 1987), a deoxy analogue of 1, is a constituent of the bulgecin glycopeptide antibiotics (Shinagawa et al., 1984; Shinagawa et al., 1985). 7a-Epialexaflorine 6, isolated from the leaves of Alexa grandiflora (Pereira et al., 1991), is the only example of an amino acid analogue of the alexines (Donohoe et al., 2008; Kato et al., 2003; Wormald et al., 1998).

The title compound (Fig. 2) was seen to adopt an envelope conformation with C4 out of the plane. The absolute configuration was determined by the use of D-glucuronolactone as the starting material for the synthesis. The molecule exists as an extensively hydrogen bonded nextwork with each molecule acting as a donor and acceptor for 5 hydrogen bonds (Fig. 3, Fig. 4). Only classical hydrogen bonding has been considered.

Experimental

The title compound was recrystallized from a mixture of hot ethanol and water: m.p. 449 K - decomposed; [α]_D²⁵ +14.7 (c, 1.13 in H₂O).

Refinement

Initial refinement of the Flack x parameter gave a value of -0.5 (10), suggesting that the absolute configuration could not be determined (Flack, 1983; Flack & Bernardinelli, 2000). Analysis of the Bijvoet differences using CRYSTALS gave the Hooft y parameter as -0.2 (7), and the probability the configuration is correct assuming the material is enantiopure was determioned to be 78.7% (Hooft et al., 2008; Thompson et al. 2008; Thompson & Watkin 2009). In the absence of significant anomalous scattering (FRIEDIF = 6.71; Flack & Shmueli, 2007), Friedel pairs were merged for the final refinement.

The H atoms were all located in a difference map, but those attached to carbon atoms were repositioned geometrically. The H atoms were initially refined with soft restraints on the bond lengths and angles to regularize their geometry (C—H in the range 0.93–0.98, N—H in the range 0.86–0.89 N—H to 0.86 O—H = 0.82 Å) and U_iso(H) (in the range 1.2–1.5 times U_eq of the parent atom), after which the positions were refined with riding constraints.

Figures

Fig. 1.

Synthetic scheme.

Fig. 2.

The title compound with displacement ellipsoids drawn at the 50% probability level. H atoms are shown as spheres of arbitary radius.

Fig. 3.

Packing diagram for the title compound projected along the b-axis.

Fig. 4.

Packing diagram for the title compound. The compound exists as an extensively hydrogen bonded nextwork.

Crystal data

C6H11NO5	Z = 1
Mr = 177.16	F(000) = 94
Triclinic, P1	Dx = 1.569 Mg m−3
Hall symbol: P 1	Melting point: not measured K
a = 5.4160 (2) Å	Mo Kα radiation, λ = 0.71073 Å
b = 5.8236 (3) Å	Cell parameters from 696 reflections
c = 6.6006 (3) Å	θ = 5–27°
α = 102.836 (2)°	µ = 0.14 mm−1
β = 104.776 (2)°	T = 150 K
γ = 102.8244 (19)°	Plate, clear_pale_colourless
V = 187.50 (2) Å3	0.25 × 0.17 × 0.06 mm

Data collection

Area diffractometer	814 reflections with I > 2σ(I)
graphite	Rint = 0.025
ω scans	θmax = 27.5°, θmin = 5.6°
Absorption correction: multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1997)	h = −7→7
Tmin = 0.94, Tmax = 0.99	k = −6→7
2314 measured reflections	l = −8→7
834 independent reflections

Refinement

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)] = 0.027	H-atom parameters constrained
wR(F2) = 0.066	Method, part 1, Chebychev polynomial, (Watkin, 1994, Prince, 1982) [weight] = 1.0/[A0*T0(x) + A1*T1(x) ··· + An-1]*Tn-1(x)] where Ai are the Chebychev coefficients listed below and x = F /Fmax Method = Robust Weighting (Prince, 1982) W = [weight] * [1-(deltaF/6*sigmaF)2]2 Ai are: 22.5 35.8 21.7 10.1 2.91
S = 1.00	(Δ/σ)max = 0.0001
834 reflections	Δρmax = 0.24 e Å−3
109 parameters	Δρmin = −0.17 e Å−3
3 restraints

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	0.1323 (3)	0.4021 (3)	0.0397 (3)	0.0170
C2	0.3330 (4)	0.5769 (4)	0.1694 (3)	0.0124
O3	0.3285 (3)	0.7782 (3)	0.2816 (3)	0.0161
C4	0.6067 (4)	0.5299 (3)	0.1892 (3)	0.0118
N5	0.8297 (3)	0.7483 (3)	0.3462 (3)	0.0120
C6	0.8425 (4)	0.7309 (4)	0.5744 (3)	0.0130
C7	1.1277 (4)	0.8313 (4)	0.7284 (3)	0.0167
O8	1.2417 (3)	1.0809 (3)	0.7415 (3)	0.0209
C9	0.7092 (4)	0.4584 (4)	0.5443 (3)	0.0150
C10	0.6269 (4)	0.3243 (4)	0.2968 (3)	0.0135
O11	0.8192 (3)	0.2063 (3)	0.2544 (3)	0.0229
O12	0.4844 (4)	0.4511 (3)	0.6175 (3)	0.0252
H41	0.6365	0.4960	0.0477	0.0144*
H61	0.7333	0.8262	0.6278	0.0169*
H72	1.1284	0.8203	0.8747	0.0191*
H71	1.2343	0.7354	0.6770	0.0194*
H91	0.8360	0.3904	0.6257	0.0183*
H101	0.4566	0.2013	0.2549	0.0154*
H81	1.2048	1.1744	0.8368	0.0313*
H51	0.7954	0.8869	0.3332	0.0177*
H52	0.9817	0.7443	0.3204	0.0178*
H111	0.8993	0.2734	0.1839	0.0347*
H121	0.4206	0.3112	0.6224	0.0383*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
O1	0.0115 (7)	0.0187 (7)	0.0178 (7)	0.0024 (5)	0.0034 (5)	0.0030 (6)
C2	0.0128 (9)	0.0137 (9)	0.0134 (9)	0.0052 (7)	0.0051 (7)	0.0074 (7)
O3	0.0153 (7)	0.0148 (7)	0.0210 (7)	0.0075 (6)	0.0074 (5)	0.0057 (6)
C4	0.0113 (9)	0.0115 (8)	0.0130 (9)	0.0032 (7)	0.0050 (7)	0.0032 (7)
N5	0.0123 (8)	0.0098 (7)	0.0150 (8)	0.0039 (6)	0.0052 (6)	0.0042 (6)
C6	0.0142 (9)	0.0115 (8)	0.0136 (9)	0.0030 (7)	0.0053 (7)	0.0041 (7)
C7	0.0154 (9)	0.0161 (9)	0.0152 (9)	0.0013 (8)	0.0023 (7)	0.0042 (8)
O8	0.0246 (8)	0.0151 (8)	0.0190 (7)	−0.0019 (6)	0.0100 (6)	0.0020 (6)
C9	0.0173 (10)	0.0130 (9)	0.0165 (10)	0.0042 (7)	0.0066 (8)	0.0067 (7)
C10	0.0121 (9)	0.0124 (9)	0.0176 (9)	0.0049 (7)	0.0058 (7)	0.0050 (7)
O11	0.0280 (8)	0.0223 (8)	0.0356 (9)	0.0180 (7)	0.0218 (7)	0.0179 (7)
O12	0.0325 (9)	0.0164 (7)	0.0304 (9)	0.0018 (7)	0.0222 (8)	0.0056 (7)

Geometric parameters (Å, °)

O1—C2	1.264 (3)	C7—O8	1.421 (2)
C2—O3	1.249 (2)	C7—H72	0.981
C2—C4	1.545 (2)	C7—H71	0.959
C4—N5	1.498 (2)	O8—H81	0.832
C4—C10	1.532 (3)	C9—C10	1.545 (3)
C4—H41	0.972	C9—O12	1.415 (2)
N5—C6	1.517 (2)	C9—H91	0.972
N5—H51	0.885	C10—O11	1.420 (2)
N5—H52	0.886	C10—H101	0.963
C6—C7	1.515 (3)	O11—H111	0.816
C6—C9	1.535 (3)	O12—H121	0.823
C6—H61	0.973
O1—C2—O3	126.24 (18)	C6—C7—O8	111.22 (16)
O1—C2—C4	115.43 (17)	C6—C7—H72	108.8
O3—C2—C4	118.32 (17)	O8—C7—H72	109.4
C2—C4—N5	110.92 (15)	C6—C7—H71	109.8
C2—C4—C10	109.46 (14)	O8—C7—H71	108.5
N5—C4—C10	103.55 (15)	H72—C7—H71	109.1
C2—C4—H41	111.2	C7—O8—H81	110.0
N5—C4—H41	108.5	C6—C9—C10	106.41 (15)
C10—C4—H41	113.0	C6—C9—O12	106.33 (16)
C4—N5—C6	106.33 (14)	C10—C9—O12	111.81 (16)
C4—N5—H51	110.5	C6—C9—H91	110.0
C6—N5—H51	109.1	C10—C9—H91	109.3
C4—N5—H52	109.8	O12—C9—H91	112.7
C6—N5—H52	111.2	C9—C10—C4	103.65 (15)
H51—N5—H52	109.8	C9—C10—O11	109.89 (16)
N5—C6—C7	110.92 (15)	C4—C10—O11	113.98 (15)
N5—C6—C9	105.61 (15)	C9—C10—H101	108.3
C7—C6—C9	114.30 (16)	C4—C10—H101	111.8
N5—C6—H61	108.0	O11—C10—H101	109.0
C7—C6—H61	109.9	C10—O11—H111	110.0
C9—C6—H61	107.9	C9—O12—H121	109.5

Hydrogen-bond geometry (Å, °)

D—H···A	D—H	H···A	D···A	D—H···A
C7—H71···O12i	0.96	2.39	3.328 (3)	166
C10—H101···O3ii	0.96	2.47	3.199 (3)	133
O8—H81···O1iii	0.83	1.85	2.679 (3)	175
N5—H51···O11iv	0.88	2.03	2.873 (3)	160
N5—H52···O3i	0.89	1.93	2.814 (3)	173
O11—H111···O1i	0.82	1.89	2.696 (3)	170
O12—H121···O8v	0.82	1.91	2.668 (3)	154

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