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Acta Crystallographica Section E: Structure Reports Online logoLink to Acta Crystallographica Section E: Structure Reports Online
. 2009 Feb 25;65(Pt 3):o610–o611. doi: 10.1107/S1600536809006357

(4S,5R,6R)-Methyl 4-hydr­oxy-4,5-iso­propyl­idenedioxy-4,5,6,7-tetra­hydro-1,2,3-triazolo[1,5-a]pyridine-3-carboxyl­ate

Sarah F Jenkinson a,*, Jennifer R Fenton a, K Victoria Booth a, George W J Fleet a, David J Watkin b
PMCID: PMC2968499  PMID: 21582263

Abstract

X-ray crystallography confirmed the structure of the title triazole, C11H15N3O5, formed from a single-step reaction of a sugar azide with a brominated ylid. The absolute configuration was determined by the use of d-ribose as the starting material. The six-membered ring is in a half-chair conformation. The crystal structure exists as chains of O—H⋯O hydrogen-bonded moleclues running parallel to the b axis.

Related literature

For imino sugars, see: Asano et al. (2000 ▶); Watson et al. (2001 ▶). For sugar tetra­zoles, see: Brandstetter et al. (1995 ▶); Davis et al. (1995 ▶); Ermert et al. (1991 ▶). For sugar triazoles, see: Caravano et al. (2007 ▶); Krivopalov & Shkurko (2005 ▶); Krulle et al. (1997 ▶); Marco-Contelles & Rodriguez-Fernandez (2001 ▶, 2002 ▶); Oikonomakos (2002 ▶); Tatsuta et al. (1996 ▶). For related literature, see: Görbitz (1999 ▶); Larson (1970 ▶).graphic file with name e-65-0o610-scheme1.jpg

Experimental

Crystal data

  • C11H15N3O5

  • M r = 269.26

  • Monoclinic, Inline graphic

  • a = 8.0587 (3) Å

  • b = 7.3797 (3) Å

  • c = 10.9785 (5) Å

  • β = 96.2740 (18)°

  • V = 648.99 (5) Å3

  • Z = 2

  • Mo Kα radiation

  • μ = 0.11 mm−1

  • T = 150 K

  • 0.60 × 0.15 × 0.03 mm

Data collection

  • Nonius KappaCCD diffractometer

  • Absorption correction: multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1997 ▶) T min = 0.82, T max = 1.00 (expected range = 0.817–0.997)

  • 9525 measured reflections

  • 1595 independent reflections

  • 1219 reflections with I > 2σ(I)

  • R int = 0.059

Refinement

  • R[F 2 > 2σ(F 2)] = 0.037

  • wR(F 2) = 0.082

  • S = 0.96

  • 1595 reflections

  • 173 parameters

  • 1 restraint

  • H-atom parameters constrained

  • Δρmax = 0.30 e Å−3

  • Δρmin = −0.31 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

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809006357/lh2778sup1.cif

e-65-0o610-sup1.cif (15.9KB, cif)

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809006357/lh2778Isup2.hkl

e-65-0o610-Isup2.hkl (80.1KB, hkl)

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
O19—H191⋯O4i 0.84 1.96 2.782 (4) 163
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Symmetry code: (i) Inline graphic.

Acknowledgments

The authors wish to thank the Oxford University Crystallography Service for use of the instruments.

supplementary crystallographic information

Comment

Sugars with the ring oxygen replaced by nitrogen comprise a large family of both natural products and synthetic analogues which inhibit sugar metabolizing enzymes (Asano et al., 2000; Watson et al., 2001), including compounds which incorporate a tetrazole (Ermert et al., 1991; Davis et al., 1995; Brandstetter et al., 1995) or triazole (Tatsuta et al., 1996; Marco-Contelles & Rodriguez-Fernandez, 2002; Caravano et al., 2007; Krivpalov & Shkurko, 2007) fused to the pyranose ring. Some sugar triazoles have potential as glycogen phosphorylase inhibitors (Oikonomakos, 2002). Usually the synthesis of pyranose triazoles requires many steps (Marco-Contelles & Rodriguez-Fernandez, 2001; Krulle et al., 1997).

A single step synthesis (see Fig. 1) has been developed in which an azidolactol 1 was reacted with Ph3P=CBrCOOMe; the open chain form 2 underwent a Wittig reaction to give 3 which was followed by an intramolecular 1,3-dipolar addition of the azide to the alkene to afford 4. Subsequent elimination of HBr gave the target compound 5. The structure of the product 5, including the relative configuration of the three chiral centers was confirmed by X-ray crystallographic analysis. The absolute configuration was determined by the use of D-ribose as the starting material for the preparation of azidolactol 1.

The crystal structure of 5 exisits as chains of O—H···O hydrogen bonded moleclues lying parallel to the b-axis. Only classical hydrogen bonding has been considered. The 6-membered ring exists in a half-chair conformation.

Experimental

The title compound was recrystallized by vapour diffusion from a mixture of ether and cyclohexane: m.p. 413–415 K; [α]D21 -140.7 (c, 1.01 in CHCl3).

Refinement

In the absence of significant anomalous scattering, Friedel pairs were merged and the absolute configuration was assigned from the starting material.

The relatively large ratio of minimum to maximum corrections applied in the multiscan process (1:1.21) reflect changes in the illuminated volume of the crystal. Changes in illuminated volume were kept to a minimum, and were taken into account (Görbitz, 1999) by the multi-scan inter-frame scaling (DENZO/SCALEPACK, Otwinowski & Minor, 1997).

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, 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.

Figures

Fig. 1.

Fig. 1.

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Synthetic Scheme.

Fig. 2.

Fig. 2.

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The molecluar structure showing the crystallographic labelling scheme and displacement ellipsoids drawn at the 50% probability level. H atoms are shown as spheres of arbitary radius.

Fig. 3.

Fig. 3.

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Part of the crystal structure of the title compound projected along the a-axis. Hydrogen bonds are indicated by dotted lines.

Crystal data

C11H15N3O5 F(000) = 284
Mr = 269.26 Dx = 1.378 Mg m−3
Monoclinic, P21 Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb Cell parameters from 1565 reflections
a = 8.0587 (3) Å θ = 5–27°
b = 7.3797 (3) Å µ = 0.11 mm−1
c = 10.9785 (5) Å T = 150 K
β = 96.2740 (18)° Plate, colourless
V = 648.99 (5) Å3 0.60 × 0.15 × 0.03 mm
Z = 2
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Data collection

Nonius KappaCCD diffractometer 1219 reflections with I > 2σ(I)
graphite Rint = 0.059
ω scans θmax = 27.5°, θmin = 5.2°
Absorption correction: multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1997) h = −10→10
Tmin = 0.82, Tmax = 1.00 k = −9→9
9525 measured reflections l = −14→14
1595 independent reflections
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Refinement

Refinement on F2 Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full H-atom parameters constrained
R[F2 > 2σ(F2)] = 0.037 Method = Modified Sheldrick w = 1/[σ2(F2) + (0.04P)2 + 0.06P], where P = [max(Fo2,0) + 2Fc2]/3
wR(F2) = 0.082 (Δ/σ)max = 0.0001
S = 0.97 Δρmax = 0.30 e Å−3
1595 reflections Δρmin = −0.31 e Å−3
173 parameters Extinction correction: Larson (1970), Equation 22
1 restraint Extinction coefficient: 120 (30)
Primary atom site location: structure-invariant direct methods
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Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

x y z Uiso*/Ueq
O1 0.2044 (2) 0.3385 (2) 0.12370 (17) 0.0348
C2 0.3680 (3) 0.2921 (3) 0.0939 (2) 0.0259
C3 0.4700 (3) 0.4559 (3) 0.14365 (19) 0.0263
O4 0.3535 (2) 0.6018 (2) 0.12971 (16) 0.0369
C5 0.1853 (3) 0.5296 (3) 0.1071 (3) 0.0371
C6 0.1173 (3) 0.5757 (4) −0.0230 (3) 0.0481
C7 0.0820 (4) 0.5983 (5) 0.2022 (3) 0.0711
C8 0.5404 (3) 0.4306 (3) 0.27502 (19) 0.0274
N9 0.5115 (2) 0.2809 (3) 0.33823 (15) 0.0314
N10 0.5960 (3) 0.2829 (4) 0.45255 (16) 0.0404
N11 0.6780 (2) 0.4367 (3) 0.46271 (17) 0.0393
C12 0.6470 (3) 0.5312 (3) 0.35555 (19) 0.0301
C13 0.7152 (3) 0.7105 (4) 0.3339 (2) 0.0347
O14 0.6759 (2) 0.7985 (3) 0.24224 (16) 0.0410
O15 0.8253 (2) 0.7650 (3) 0.42672 (17) 0.0493
C16 0.8993 (4) 0.9424 (5) 0.4125 (3) 0.0619
C17 0.4111 (3) 0.1253 (4) 0.2922 (2) 0.0340
C18 0.4225 (3) 0.1151 (3) 0.1552 (2) 0.0282
O19 0.3191 (2) −0.0250 (2) 0.10143 (15) 0.0345
H21 0.3716 0.2823 0.0030 0.0326*
H31 0.5628 0.4800 0.0923 0.0335*
H62 0.1213 0.7081 −0.0306 0.0684*
H61 0.0013 0.5339 −0.0390 0.0679*
H63 0.1873 0.5166 −0.0791 0.0683*
H72 0.0760 0.7296 0.1946 0.1122*
H71 −0.0294 0.5466 0.1898 0.1121*
H73 0.1367 0.5658 0.2826 0.1119*
H163 0.9999 0.9506 0.4700 0.0913*
H162 0.9284 0.9553 0.3294 0.0911*
H161 0.8193 1.0353 0.4304 0.0913*
H172 0.2930 0.1423 0.3074 0.0432*
H171 0.4592 0.0151 0.3327 0.0435*
H181 0.5417 0.0915 0.1425 0.0336*
H191 0.3489 −0.1327 0.1166 0.0521*
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Atomic displacement parameters (Å2)

U11 U22 U33 U12 U13 U23
O1 0.0270 (8) 0.0198 (9) 0.0582 (11) 0.0004 (7) 0.0067 (7) 0.0020 (7)
C2 0.0241 (11) 0.0212 (11) 0.0325 (11) 0.0008 (10) 0.0032 (8) −0.0010 (11)
C3 0.0298 (11) 0.0224 (12) 0.0259 (11) 0.0021 (10) −0.0007 (9) 0.0011 (10)
O4 0.0340 (9) 0.0205 (9) 0.0524 (11) 0.0020 (8) −0.0125 (7) −0.0004 (8)
C5 0.0267 (12) 0.0178 (12) 0.0658 (17) 0.0013 (10) 0.0007 (11) −0.0001 (12)
C6 0.0357 (13) 0.0268 (14) 0.0762 (19) −0.0026 (12) −0.0191 (13) 0.0064 (14)
C7 0.075 (2) 0.041 (2) 0.105 (3) 0.0097 (18) 0.0425 (19) −0.0053 (19)
C8 0.0270 (11) 0.0247 (12) 0.0305 (11) 0.0084 (11) 0.0040 (9) −0.0028 (11)
N9 0.0372 (10) 0.0314 (11) 0.0256 (9) 0.0035 (10) 0.0040 (8) 0.0024 (9)
N10 0.0491 (12) 0.0475 (14) 0.0241 (9) 0.0073 (12) 0.0023 (8) 0.0009 (11)
N11 0.0427 (11) 0.0465 (14) 0.0279 (10) 0.0110 (12) −0.0003 (8) −0.0067 (11)
C12 0.0294 (11) 0.0315 (14) 0.0283 (12) 0.0091 (10) −0.0011 (9) −0.0061 (11)
C13 0.0262 (11) 0.0346 (14) 0.0413 (14) 0.0068 (11) −0.0055 (10) −0.0129 (12)
O14 0.0382 (9) 0.0298 (10) 0.0524 (11) 0.0004 (9) −0.0062 (8) −0.0029 (10)
O15 0.0406 (10) 0.0451 (13) 0.0576 (11) 0.0030 (9) −0.0157 (8) −0.0195 (10)
C16 0.0454 (15) 0.0440 (19) 0.091 (2) −0.0055 (16) −0.0167 (14) −0.0262 (18)
C17 0.0404 (13) 0.0262 (13) 0.0366 (13) 0.0005 (11) 0.0099 (10) 0.0045 (11)
C18 0.0313 (11) 0.0196 (12) 0.0335 (12) 0.0020 (10) 0.0030 (9) 0.0005 (10)
O19 0.0413 (9) 0.0137 (8) 0.0481 (10) 0.0003 (7) 0.0036 (7) −0.0011 (7)
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Geometric parameters (Å, °)

O1—C2 1.434 (3) C8—C12 1.380 (3)
O1—C5 1.429 (3) N9—N10 1.361 (3)
C2—C3 1.529 (3) N9—C17 1.463 (3)
C2—C18 1.512 (3) N10—N11 1.312 (3)
C2—H21 1.004 N11—C12 1.367 (3)
C3—O4 1.426 (3) C12—C13 1.462 (4)
C3—C8 1.503 (3) C13—O14 1.211 (3)
C3—H31 1.000 C13—O15 1.338 (3)
O4—C5 1.452 (3) O15—C16 1.454 (4)
C5—C6 1.512 (4) C16—H163 0.973
C5—C7 1.494 (4) C16—H162 0.971
C6—H62 0.981 C16—H161 0.976
C6—H61 0.982 C17—C18 1.519 (3)
C6—H63 0.982 C17—H172 0.992
C7—H72 0.973 C17—H171 0.986
C7—H71 0.971 C18—O19 1.416 (3)
C7—H73 0.973 C18—H181 1.001
C8—N9 1.339 (3) O19—H191 0.842
C2—O1—C5 107.18 (19) C3—C8—C12 133.8 (2)
O1—C2—C3 101.66 (18) N9—C8—C12 104.07 (19)
O1—C2—C18 109.52 (18) C8—N9—N10 111.8 (2)
C3—C2—C18 113.92 (17) C8—N9—C17 126.16 (18)
O1—C2—H21 111.8 N10—N9—C17 122.0 (2)
C3—C2—H21 109.8 N9—N10—N11 106.53 (19)
C18—C2—H21 110.0 N10—N11—C12 108.96 (19)
C2—C3—O4 103.68 (16) C8—C12—N11 108.7 (2)
C2—C3—C8 112.1 (2) C8—C12—C13 127.0 (2)
O4—C3—C8 111.83 (18) N11—C12—C13 124.4 (2)
C2—C3—H31 110.2 C12—C13—O14 123.5 (2)
O4—C3—H31 109.2 C12—C13—O15 112.2 (2)
C8—C3—H31 109.6 O14—C13—O15 124.3 (3)
C3—O4—C5 109.44 (17) C13—O15—C16 115.8 (2)
O4—C5—O1 104.75 (19) O15—C16—H163 108.0
O4—C5—C6 108.3 (2) O15—C16—H162 109.4
O1—C5—C6 111.5 (2) H163—C16—H162 109.5
O4—C5—C7 109.7 (2) O15—C16—H161 108.8
O1—C5—C7 107.8 (2) H163—C16—H161 110.4
C6—C5—C7 114.3 (2) H162—C16—H161 110.6
C5—C6—H62 107.0 N9—C17—C18 106.86 (19)
C5—C6—H61 109.7 N9—C17—H172 110.3
H62—C6—H61 109.7 C18—C17—H172 109.6
C5—C6—H63 108.6 N9—C17—H171 108.5
H62—C6—H63 111.3 C18—C17—H171 110.0
H61—C6—H63 110.4 H172—C17—H171 111.4
C5—C7—H72 107.7 C17—C18—C2 110.60 (19)
C5—C7—H71 110.2 C17—C18—O19 110.65 (19)
H72—C7—H71 110.0 C2—C18—O19 108.43 (17)
C5—C7—H73 108.6 C17—C18—H181 108.0
H72—C7—H73 109.7 C2—C18—H181 108.9
H71—C7—H73 110.5 O19—C18—H181 110.2
C3—C8—N9 122.1 (2) C18—O19—H191 117.7
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Hydrogen-bond geometry (Å, °)

D—H···A D—H H···A D···A D—H···A
C3—H31···O19i 1.00 2.42 3.339 (4) 152
C16—H161···N10ii 0.98 2.59 3.567 (4) 174
O19—H191···O4iii 0.84 1.96 2.782 (4) 163
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Symmetry codes: (i) −x+1, y+1/2, −z; (ii) x, y+1, z; (iii) x, y−1, z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: LH2778).

References

  1. Altomare, A., Cascarano, G., Giacovazzo, C., Guagliardi, A., Burla, M. C., Polidori, G. & Camalli, M. (1994). J. Appl. Cryst.27, 435.
  2. Asano, N., Nash, R. J., Molyneux, R. J. & Fleet, G. W. J. (2000). Tetrahedron Asymmetry, 11, 1645–1680.
  3. Betteridge, P. W., Carruthers, J. R., Cooper, R. I., Prout, K. & Watkin, D. J. (2003). J. Appl. Cryst.36, 1487.
  4. Brandstetter, T. W., Davis, B., Hyett, D., Smith, C., Hackett, L., Winchester, B. G. & Fleet, G. W. J. (1995). Tetrahedron Lett.36, 7511–7514.
  5. Caravano, A., Baillieul, D., Ansiaux, C., Pan, W. D., Kovensky, J., Sinay, P. & Vincent, S. P. (2007). Tetrahedron, 63, 2070–2077.
  6. Davis, B., Brandstetter, T. W., Smith, C., Hackett, L., Winchester, B. G. & Fleet, G. W. J. (1995). Tetrahedron Lett.36, 7507–7510.
  7. Ermert, P. & Vasella, A. (1991). Helv. Chim. Acta, 74, 2043–2053.
  8. Görbitz, C. H. (1999). Acta Cryst. B55, 1090–1098. [DOI] [PubMed]
  9. Krivopalov, V. P. & Shkurko, O. P. (2005). Usp. Khim.74, 369–410.
  10. Krulle, T. M., de la Fuente, C., Pickering, L., Aplin, R. A., Tsitsanou, K. E., Zographos, S. E., Oikonomakos, N. G., Nash, R. J., Griffiths, R. C. & Fleet, G. W. J. (1997). Tetrahedron Asymmetry, 8, 3807–3820.
  11. Larson, A. C. (1970). Crystallographic Computing, edited by F. R. Ahmed, S. R. Hall & C. P. Huber, pp. 291–294. Copenhagen: Munksgaard.
  12. Marco-Contelles, J. & Rodriguez-Fernandez, M. (2001). J. Org. Chem.66, 3717–3725. [DOI] [PubMed]
  13. Marco-Contelles, J. & Rodriguez-Fernandez, M. (2002). Tetrahedron Lett.41, 381–384.
  14. Nonius (2001). COLLECT Nonius BV, Delft, The Netherlands.
  15. Oikonomakos, N. G. (2002). Curr. Protein Peptide Sci.3, 561–586. [DOI] [PubMed]
  16. 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.
  17. Tatsuta, K., Ikeda, Y. & Miura, S. (1996). J. Antibiot.49, 836–838. [DOI] [PubMed]
  18. Watkin, D. J., Prout, C. K. & Pearce, L. J. (1996). CAMERON Chemical Crystallography Laboratory, Oxford, England.
  19. Watson, A. A., Fleet, G. W. J., Asano, N., Molyneux, R. J. & Nash, R. J. (2001). Phytochemistry, 56, 265–295. [DOI] [PubMed]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809006357/lh2778sup1.cif

e-65-0o610-sup1.cif (15.9KB, cif)

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809006357/lh2778Isup2.hkl

e-65-0o610-Isup2.hkl (80.1KB, hkl)

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

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography

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