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Acta Cryst. (2009). E65, o2418-o2419    [ doi:10.1107/S1600536809035636 ]

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

D. Best, S. F. Jenkinson, A. L. Thompson, D. J. Watkin, F. X. Wilson, R. J. Nash and G. W. J. Fleet

Abstract top

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.

Comment top

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.

Related literature top

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), Bashyal, Chow & 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, Fellows & Fleet (1987), 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 related literature, see: Flack (1983); Flack & Bernardinelli (2000); Flack & Shmueli (2007); Hooft et al. (2008); Prince (1982); Shinagawa et al. (1984, 1985); Thompson & Watkin (2009); Thompson et al. (2008); Watkin (1994).

Experimental top

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 top

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 Uiso(H) (in the range 1.2–1.5 times Ueq of the parent atom), after which the positions were refined with riding constraints.

Computing details top

Data collection: COLLECT (Nonius, 2001).; cell refinement: DENZO/SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO/SCALEPACK (Otwinowski & Minor, 1997); 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 (Betteridge et al., 2003).

Figures top
[Figure 1] Fig. 1. Synthetic scheme.
[Figure 2] Fig. 2. The title compound with displacement ellipsoids drawn at the 50% probability level. H atoms are shown as spheres of arbitary radius.
[Figure 3] Fig. 3. Packing diagram for the title compound projected along the b-axis.
[Figure 4] Fig. 4. Packing diagram for the title compound. The compound exists as an extensively hydrogen bonded nextwork.
(2S,3R,4R,5R)-3,4-Dihydroxy-5- (hydroxymethyl)pyrrolidine-2-carboxylic acid top
Crystal data top
C6H11NO5Z = 1
Mr = 177.16F(000) = 94
Triclinic, P1Dx = 1.569 Mg m−3
Hall symbol: P 1Melting point: not measured K
a = 5.4160 (2) ÅMo Kα radiation, λ = 0.71073 Å
b = 5.8236 (3) ÅCell parameters from 696 reflections
c = 6.6006 (3) Åθ = 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) Å30.25 × 0.17 × 0.06 mm
Data collection top
Area
diffractometer		814 reflections with I > 2σ(I)
graphiteRint = 0.025
ω scansθmax = 27.5°, θmin = 5.6°
Absorption correction: multi-scan
(DENZO/SCALEPACK; Otwinowski & Minor, 1997)		h = −7→7
Tmin = 0.94, Tmax = 0.99k = −6→7
2314 measured reflectionsl = −8→7
834 independent reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.027H-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 reflectionsΔρmax = 0.24 e Å−3
109 parametersΔρmin = −0.17 e Å−3
3 restraints
Crystal data top
C6H11NO5γ = 102.8244 (19)°
Mr = 177.16V = 187.50 (2) Å3
Triclinic, P1Z = 1
a = 5.4160 (2) ÅMo Kα radiation
b = 5.8236 (3) ŵ = 0.14 mm−1
c = 6.6006 (3) ÅT = 150 K
α = 102.836 (2)°0.25 × 0.17 × 0.06 mm
β = 104.776 (2)°
Data collection top
Area
diffractometer		834 independent reflections
Absorption correction: multi-scan
(DENZO/SCALEPACK; Otwinowski & Minor, 1997)		814 reflections with I > 2σ(I)
Tmin = 0.94, Tmax = 0.99Rint = 0.025
2314 measured reflectionsθmax = 27.5°
Refinement top
R[F2 > 2σ(F2)] = 0.027H-atom parameters constrained
wR(F2) = 0.066Δρmax = 0.24 e Å−3
S = 1.00Δρmin = −0.17 e Å−3
834 reflectionsAbsolute structure: ?
109 parametersFlack parameter: ?
3 restraintsRogers parameter: ?
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.1323 (3)0.4021 (3)0.0397 (3)0.0170
C20.3330 (4)0.5769 (4)0.1694 (3)0.0124
O30.3285 (3)0.7782 (3)0.2816 (3)0.0161
C40.6067 (4)0.5299 (3)0.1892 (3)0.0118
N50.8297 (3)0.7483 (3)0.3462 (3)0.0120
C60.8425 (4)0.7309 (4)0.5744 (3)0.0130
C71.1277 (4)0.8313 (4)0.7284 (3)0.0167
O81.2417 (3)1.0809 (3)0.7415 (3)0.0209
C90.7092 (4)0.4584 (4)0.5443 (3)0.0150
C100.6269 (4)0.3243 (4)0.2968 (3)0.0135
O110.8192 (3)0.2063 (3)0.2544 (3)0.0229
O120.4844 (4)0.4511 (3)0.6175 (3)0.0252
H410.63650.49600.04770.0144*
H610.73330.82620.62780.0169*
H721.12840.82030.87470.0191*
H711.23430.73540.67700.0194*
H910.83600.39040.62570.0183*
H1010.45660.20130.25490.0154*
H811.20481.17440.83680.0313*
H510.79540.88690.33320.0177*
H520.98170.74430.32040.0178*
H1110.89930.27340.18390.0347*
H1210.42060.31120.62240.0383*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0115 (7)0.0187 (7)0.0178 (7)0.0024 (5)0.0034 (5)0.0030 (6)
C20.0128 (9)0.0137 (9)0.0134 (9)0.0052 (7)0.0051 (7)0.0074 (7)
O30.0153 (7)0.0148 (7)0.0210 (7)0.0075 (6)0.0074 (5)0.0057 (6)
C40.0113 (9)0.0115 (8)0.0130 (9)0.0032 (7)0.0050 (7)0.0032 (7)
N50.0123 (8)0.0098 (7)0.0150 (8)0.0039 (6)0.0052 (6)0.0042 (6)
C60.0142 (9)0.0115 (8)0.0136 (9)0.0030 (7)0.0053 (7)0.0041 (7)
C70.0154 (9)0.0161 (9)0.0152 (9)0.0013 (8)0.0023 (7)0.0042 (8)
O80.0246 (8)0.0151 (8)0.0190 (7)−0.0019 (6)0.0100 (6)0.0020 (6)
C90.0173 (10)0.0130 (9)0.0165 (10)0.0042 (7)0.0066 (8)0.0067 (7)
C100.0121 (9)0.0124 (9)0.0176 (9)0.0049 (7)0.0058 (7)0.0050 (7)
O110.0280 (8)0.0223 (8)0.0356 (9)0.0180 (7)0.0218 (7)0.0179 (7)
O120.0325 (9)0.0164 (7)0.0304 (9)0.0018 (7)0.0222 (8)0.0056 (7)
Geometric parameters (Å, °) top
O1—C21.264 (3)C7—O81.421 (2)
C2—O31.249 (2)C7—H720.981
C2—C41.545 (2)C7—H710.959
C4—N51.498 (2)O8—H810.832
C4—C101.532 (3)C9—C101.545 (3)
C4—H410.972C9—O121.415 (2)
N5—C61.517 (2)C9—H910.972
N5—H510.885C10—O111.420 (2)
N5—H520.886C10—H1010.963
C6—C71.515 (3)O11—H1110.816
C6—C91.535 (3)O12—H1210.823
C6—H610.973
O1—C2—O3126.24 (18)C6—C7—O8111.22 (16)
O1—C2—C4115.43 (17)C6—C7—H72108.8
O3—C2—C4118.32 (17)O8—C7—H72109.4
C2—C4—N5110.92 (15)C6—C7—H71109.8
C2—C4—C10109.46 (14)O8—C7—H71108.5
N5—C4—C10103.55 (15)H72—C7—H71109.1
C2—C4—H41111.2C7—O8—H81110.0
N5—C4—H41108.5C6—C9—C10106.41 (15)
C10—C4—H41113.0C6—C9—O12106.33 (16)
C4—N5—C6106.33 (14)C10—C9—O12111.81 (16)
C4—N5—H51110.5C6—C9—H91110.0
C6—N5—H51109.1C10—C9—H91109.3
C4—N5—H52109.8O12—C9—H91112.7
C6—N5—H52111.2C9—C10—C4103.65 (15)
H51—N5—H52109.8C9—C10—O11109.89 (16)
N5—C6—C7110.92 (15)C4—C10—O11113.98 (15)
N5—C6—C9105.61 (15)C9—C10—H101108.3
C7—C6—C9114.30 (16)C4—C10—H101111.8
N5—C6—H61108.0O11—C10—H101109.0
C7—C6—H61109.9C10—O11—H111110.0
C9—C6—H61107.9C9—O12—H121109.5
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
C7—H71···O12i0.962.393.328 (3)166
C10—H101···O3ii0.962.473.199 (3)133
O8—H81···O1iii0.831.852.679 (3)175
N5—H51···O11iv0.882.032.873 (3)160
N5—H52···O3i0.891.932.814 (3)173
O11—H111···O1i0.821.892.696 (3)170
O12—H121···O8v0.821.912.668 (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.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O8—H81···O1i0.831.852.679 (3)175
N5—H51···O11ii0.882.032.873 (3)160
N5—H52···O3iii0.891.932.814 (3)173
O11—H111···O1iii0.821.892.696 (3)170
O12—H121···O8iv0.821.912.668 (3)154
Symmetry codes: (i) x+1, y+1, z+1; (ii) x, y+1, z; (iii) x+1, y, z; (iv) x−1, y−1, z.
references
References top

Altomare, A., Cascarano, G., Giacovazzo, C., Guagliardi, A., Burla, M. C., Polidori, G. & Camalli, M. (1994). J. Appl. Cryst. 27, 435.

Asano, N., Nash, R. J., Molyneux, R. J. & Fleet, G. W. J. (2000). Tetrahedron Asymmetry, 11, 1645–1680.

Bashyal, B. P., Chow, H.-F., Fellows, L. E. & Fleet, G. W. J. (1987). Tetrahedron, 43, 415–422.

Bashyal, B. P., Chow, H.-F. & Fleet, G. W. J. (1986). Tetrahedron Lett. 27, 3205–3208.

Bashyal, B. P., Chow, H.-F. & Fleet, G. W. J. (1987). Tetrahedron, 43, 423–430.

Betteridge, P. W., Carruthers, J. R., Cooper, R. I., Prout, K. & Watkin, D. J. (2003). J. Appl. Cryst. 36, 1487.

Booth, K. V., Jenkinson, S. F., Watkin, D. J., Sharp, H., Jones, P. W., Nash, R. J. & Fleet, G. W. J. (2007). Acta Cryst. E63, o3783–o3784.

di Bello, I. C., Dorling, P., Fellows, L. & Winchester, B. (1984). FEBS Lett. 176, 61–64.

Donohoe, T. J., Cheeseman, M. D., O'Riordan, T. J. C. & Kershaw, J. A. (2008). Org. Biomol. Chem. pp. 3896–3898.

Flack, H. D. (1983). Acta Cryst. A39, 876–881.

Flack, H. D. & Bernardinelli, G. (2000). J. Appl. Cryst. 33, 1143–1148.

Flack, H. D. & Shmueli, U. (2007). Acta Cryst. A63, 257–265.

Fleet, G. W. J., Fellows, L. E. & Smith, P. W. (1987). Tetrahedron, 43, 979–990.

Hooft, R. W. W., Straver, L. H. & Spek, A. L. (2008). J. Appl. Cryst. 41, 96–103.

Kato, A., Kano, E., Adachi, I., Molyneux, R. J., Watson, A. A., Nash, R. J., Fleet, G. W. J., Wormald, M. R., Kizu, H., Ikeda, K. & Asano, N. (2003). Tetrahedron Asymmetry, 14, 325–331.

Manning, K. S., Lynn, D. G., Shabanowitz, J., Fellows, L. E., Singh, M. & Schrire, B. D. (1985). J. Chem. Soc. Chem. Commun. pp. 127–129.

Nonius (2001). COLLECT. Nonius BV, Delft, The Netherlands.

Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307–326. New York: Academic Press.

Pereira, A. C. D., Kaplan, M. A. C., Maia, J. G. S., Gottlieb, O. R., Nash, R. J., Fleet, G., Pearce, L., Watkin, D. J. & Scofield, A. M. (1991). Tetrahedron, 47, 5637–5640.

Prince, E. (1982). Mathematical Techniques in Crystallography and Materials Science. New York: Springer-Verlag.

Shinagawa, S., Kasahara, F., Harada, S. & Asai, M. (1984). Tetrahedron, 40, 3465–3470.

Shinagawa, S., Maki, M., Kintaka, K., Imada, A. & Asai, M. (1985). J. Antibiot. 38, 17–23.

Thompson, A. L. & Watkin, D. J. (2009). Tetrahedron Asymmetry, 20, 712–717.

Thompson, A. L., Watkin, D. J., Gal, Z. A., Jones, L., Hollinshead, J., Jenkinson, S. F., Fleet, G. W. J. & Nash, R. J. (2008). Acta Cryst. C64, o649–o652.

Toumi, M., Couty, F. & Evano, G. (2008). Tetrahedron Lett. 49, 1175–1179.

Watkin, D. (1994). Acta Cryst. A50, 411–437.

Watkin, D. J., Prout, C. K. & Pearce, L. J. (1996). CAMERON. Chemical Crystallography Laboratory, Oxford, England.

Watson, A. A., Fleet, G. W. J., Asano, N., Molyneux, R. J. & Nash, R. J. (2001). Phytochemistry, 56, 265–295.

Wormald, M. R., Nash, R. J., Hrnciar, P., White, J. D., Molyneux, R. J. & Fleet, G. W. J. (1998). Tetrahedron Asymmetry, 9, 2549–2558.

Yoshimura, Y., Ohara, C., Imahori, T., Saito, Y., Kato, A., Miyauchi, S., Adachi, I. & Takahata, H. (2008). Bioorg. Med. Chem. 16, 8273–8286.