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Acta Crystallogr Sect E Struct Rep Online. 2009 August 1; 65(Pt 8): o1731–o1732.
Published online 2009 July 1. doi:  10.1107/S1600536809024283
PMCID: PMC2977186

(3aR,8aS,9S,9aR)-9-Hydroxy­perhydro­furo[3,2-f]indolizin-6-one

Abstract

In the title compound, C10H15NO3, the central six-membered ring of the indolizine system adopts a chair conformation, while the oxopyrrolidine and hydro­furan rings attached to the indolizine ring system have envelope conformations. In the crystal, the mol­ecules form chains parallel to the b axis via inter­molecular O—H(...)O hydrogen bonds. The absolute configuration was assigned from the synthesis.

Related literature

For general properties of indolizines see: Gundersen et al. (2007 [triangle]); Sundaram et al. (2007 [triangle]); Mikael (1999 [triangle]); Pyne (2005 [triangle]); Karanjule et al. (2006 [triangle]); Chaudhari et al. (2006 [triangle]); Martin et al. (2005 [triangle]). For the synthesis of the title compound see: Šafář et al. (2008 [triangle]). For related structures, see: Vrábel et al. (2004 [triangle]); Švorc et al. (2009 [triangle]). Camus et al. (2003 [triangle]) For puckering parameters, see: Cremer & Pople (1975 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o1731-scheme1.jpg

Experimental

Crystal data

  • C10H15NO3
  • M r = 197.23
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o1731-efi1.jpg
  • a = 6.2856 (1) Å
  • b = 6.4521 (1) Å
  • c = 11.7698 (2) Å
  • β = 98.631 (2)°
  • V = 471.92 (1) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.10 mm−1
  • T = 298 K
  • 0.45 × 0.29 × 0.04 mm

Data collection

  • Oxford Diffraction Gemini R CCD diffractometer
  • Absorption correction: analytical (Clark & Reid, 1995 [triangle]) T min = 0.962, T max = 0.996
  • 12197 measured reflections
  • 1359 independent reflections
  • 1151 reflections with I > 2σ(I)
  • R int = 0.024

Refinement

  • R[F 2 > 2σ(F 2)] = 0.032
  • wR(F 2) = 0.088
  • S = 1.09
  • 1359 reflections
  • 131 parameters
  • 1 restraint
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.18 e Å−3
  • Δρmin = −0.12 e Å−3

Data collection: CrysAlis CCD (Oxford Diffraction, 2006 [triangle]); cell refinement: CrysAlis RED (Oxford Diffraction, 2006 [triangle]); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: DIAMOND (Brandenburg, 2001 [triangle]); software used to prepare material for publication: enCIFer (Allen et al., 2004 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809024283/bg2263sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809024283/bg2263Isup2.hkl

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

Acknowledgments

The authors thank the Grant Agency of the Slovak Republic (grant Nos. 1/0161/08 and 1/0817/08) and the Structural Funds, Interreg IIIA for financial support in purchasing the diffractometer and the Development Agency under contract No. APVV-0210–07.

supplementary crystallographic information

Comment

Indolizines are electron-rich heterocycles with very low oxidation potential. Functionalized indolizines are common substructures found in biologically important natural products and synthetic pharmaceuticals. Due to the various biological functions associated with this skeleton, it has been frequently employed as a key scaffold in the drug industry (Gundersen et al., 2007). The indolizine derivatives show antibacterial, antiviral, antiherpes, anticancer, antifungal, antihelmintic and insecticidal activity (Sundaram et al., 2007). Indolizine alkaloids are excellent inhibitors of biologically important pathways. These include the binding and processing of glycoproteins, potent glycosidase inhibitory activities (Pyne, 2005), activity against AIDS virus HIV and some carcinogenic cells (Mikael, 1999). Castanospermine (Karanjule et al., 2006), swainsonine (Martin et al., 2005) and lentiginosine (Chaudhari et al., 2006) have shown respective glycosidase and mannosidase inhibitory activities, respectively. While an impressive number of total syntheses of polyhydroxylated indolizines and their non-natural analogues in chiral or racemic forms have been reported, the monohydroxylated indolizines have attracted far less attention.

Based on these facts and in contitutation of our interest in developing simple and efficient route for the synthesis of novel monohydroxylated indolizine derivatives, we report here the synthesis, molecular and crystal structure of the title compound, (I). The absolute configuration was established by synthesis and is depicted in the scheme and figure. The expected stereochemistry of atoms C5, C6, C7 and C10 was confirmed as S, S, R and R, respectively (Fig. 1). The central six-membered ring is not planar and adopts a chair conformation (Cremer & Pople, 1975). A calculation of least-squares planes shows that this ring is puckered in such a manner that the four atoms C5, C6, C10 and C11 are coplanar to within 0.019 (2) Å, while atoms N1 and C7 are displaced from this plane on opposite sides, with out-of-plane displacements of -0.591 (2) and 0.565 (1) Å, respectively. The oxopyrrolidine and hydrofuran rings are each distorted towards an envelope conformation, with atoms C4 and C10 as the flaps. The displacements of atoms C4 and C10 from the mean planes of the remaining four atoms are 0.316 (2) and 0.642 (2) Å, respectively. The central six-membered N-ring is approximately perpendicular to the hydrofuran ring (dihedral angle between plane defined by atoms C5, C6, C10 and C11 and plane defined by atoms C7, O3, C8 and C9) is 82.2 (1)°. As was mentioned in previous papers (Vrábel et al., 2004; Švorc et al., 2009), the N1—C5 and N1—C11 bonds are approximately equivalent and both are much longer than the N1—C2 bond. Atom N1 is sp2-hybridized, as evidenced by the sum of the valence angles around it (357.3 (2)°). These data are consistent with conjugation of the lone-pair electrons on N1 with the adjacent carbonyl, similar to what is observed for amides. Intermolecular O—H···O hydrogen bonds link the molecules of (I) into extended chains, which run parallel to the b axis (Fig. 2) and help to stabilize the crystal structure of the compound. Atom O2 participates as acceptor and atom O3 as donator in these intermolecular hydrogen bonds. Bond lengths and angles in the indolizine ring system are in good agreement with values from the literature (Camus et al., 2003).

Experimental

The title compound (3aR,8aS,9S,9aR)-9-hydroxyoctahydrofuro[3,2-f]indolizin- 6(4H)-one was prepared according literature procedures of Šafář et al. (2008).

Refinement

Atom H2 was refined isotropically. All other H atoms were positioned geometrically and treated as riding atoms, with C—H distances in the range 0.97 - 0.98Å and Uiso set at 1.2Ueq of the parent atom. The absolute configuration could not be reliably determined for this compound using Mo radiation, and has been assigned according to the synthesis; Friedel pairs have been merged.

Figures

Fig. 1.
Molecular structure of (I) with the atomic numbering scheme. Displacement ellipsoids are drawn at the 50% probability level (Brandenburg, 2001).
Fig. 2.
Packing view of (I), projected along a and showing the formation of chains running along b.

Crystal data

C10H15NO3F(000) = 212
Mr = 197.23Dx = 1.388 Mg m3
Monoclinic, P21Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ybCell parameters from 7268 reflections
a = 6.2856 (1) Åθ = 3.2–29.4°
b = 6.4521 (1) ŵ = 0.10 mm1
c = 11.7698 (2) ÅT = 298 K
β = 98.631 (2)°Block, white
V = 471.92 (1) Å30.45 × 0.29 × 0.04 mm
Z = 2

Data collection

Oxford Diffraction Gemini R CCD diffractometer1359 independent reflections
Radiation source: fine-focus sealed tube1151 reflections with I > 2σ(I)
graphiteRint = 0.024
Detector resolution: 10.4340 pixels mm-1θmax = 29.5°, θmin = 3.5°
Rotation method data acquisition using ω and [var phi] scansh = −8→8
Absorption correction: analytical (Clark & Reid, 1995)k = −8→8
Tmin = 0.962, Tmax = 0.996l = −16→16
12197 measured reflections

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.032Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.088H atoms treated by a mixture of independent and constrained refinement
S = 1.09w = 1/[σ2(Fo2) + (0.0589P)2 + 0.002P] where P = (Fo2 + 2Fc2)/3
1359 reflections(Δ/σ)max < 0.001
131 parametersΔρmax = 0.18 e Å3
1 restraintΔρmin = −0.12 e Å3

Special details

Experimental. (face-indexed; Oxford Diffraction, 2006)
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

xyzUiso*/Ueq
C20.4873 (3)0.2817 (3)0.72325 (14)0.0411 (4)
C30.4877 (3)0.1873 (3)0.84157 (15)0.0459 (4)
H3B0.34670.13320.84940.055*
H3A0.59210.07590.85500.055*
C40.5484 (3)0.3645 (3)0.92481 (13)0.0387 (4)
H4B0.64700.31770.99120.046*
H4A0.42160.42250.95060.046*
C50.6564 (2)0.5248 (3)0.85636 (11)0.0332 (3)
H5A0.61050.66470.87420.040*
C60.9007 (2)0.5135 (3)0.87248 (12)0.0344 (3)
H6A0.94260.36840.86500.041*
C70.9925 (2)0.6393 (3)0.78316 (14)0.0380 (4)
H7A1.14730.61170.79000.046*
C80.9599 (3)0.9602 (3)0.69052 (17)0.0550 (5)
H8B1.08491.04940.69340.066*
H8A0.83151.04440.67230.066*
C90.9646 (3)0.7923 (4)0.60051 (16)0.0532 (5)
H9B1.10880.77320.58230.064*
H9A0.86800.82510.53060.064*
C100.8887 (3)0.5997 (3)0.65890 (13)0.0431 (4)
H10A0.94440.47260.62860.052*
C110.6434 (3)0.5962 (3)0.64646 (13)0.0468 (4)
H11B0.58980.73670.65000.056*
H11A0.58470.53830.57230.056*
N10.5732 (2)0.4730 (2)0.73730 (11)0.0396 (3)
O10.4241 (2)0.1993 (3)0.63124 (11)0.0624 (4)
O20.9924 (2)0.5850 (2)0.98351 (11)0.0487 (3)
H2A0.993 (4)0.493 (5)1.031 (2)0.060 (7)*
O30.9608 (2)0.85665 (19)0.79966 (10)0.0471 (3)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C20.0366 (7)0.0539 (10)0.0319 (7)−0.0097 (7)0.0025 (6)0.0024 (7)
C30.0520 (9)0.0514 (10)0.0339 (8)−0.0129 (8)0.0044 (7)0.0047 (7)
C40.0391 (7)0.0485 (10)0.0291 (7)−0.0010 (7)0.0071 (6)0.0031 (7)
C50.0373 (7)0.0380 (8)0.0242 (6)0.0012 (6)0.0045 (5)−0.0003 (6)
C60.0375 (7)0.0378 (8)0.0263 (7)0.0009 (6)−0.0004 (5)−0.0011 (7)
C70.0325 (7)0.0471 (10)0.0345 (8)0.0000 (7)0.0057 (6)0.0001 (7)
C80.0631 (11)0.0518 (11)0.0482 (10)−0.0164 (9)0.0025 (8)0.0130 (9)
C90.0532 (9)0.0700 (13)0.0378 (9)−0.0141 (10)0.0116 (7)0.0122 (9)
C100.0545 (9)0.0477 (10)0.0290 (7)−0.0050 (8)0.0129 (6)−0.0009 (7)
C110.0544 (9)0.0563 (10)0.0271 (7)−0.0143 (9)−0.0026 (6)0.0087 (8)
N10.0407 (7)0.0506 (8)0.0255 (6)−0.0095 (6)−0.0019 (5)0.0053 (6)
O10.0721 (8)0.0765 (10)0.0357 (6)−0.0308 (8)−0.0011 (6)−0.0067 (7)
O20.0583 (7)0.0559 (8)0.0275 (6)−0.0166 (6)−0.0082 (5)0.0040 (6)
O30.0619 (7)0.0427 (7)0.0362 (6)−0.0111 (6)0.0053 (5)0.0005 (6)

Geometric parameters (Å, °)

C2—O11.218 (2)C7—C101.531 (2)
C2—N11.347 (2)C7—H7A0.9800
C2—C31.520 (2)C8—O31.447 (2)
C3—C41.517 (3)C8—C91.519 (3)
C3—H3B0.9700C8—H8B0.9700
C3—H3A0.9700C8—H8A0.9700
C4—C51.530 (2)C9—C101.531 (3)
C4—H4B0.9700C9—H9B0.9700
C4—H4A0.9700C9—H9A0.9700
C5—N11.4591 (18)C10—C111.527 (2)
C5—C61.5204 (19)C10—H10A0.9800
C5—H5A0.9800C11—N11.453 (2)
C6—O21.4238 (17)C11—H11B0.9700
C6—C71.510 (2)C11—H11A0.9700
C6—H6A0.9800O2—H2A0.82 (3)
C7—O31.433 (2)
O1—C2—N1125.45 (17)C6—C7—H7A108.9
O1—C2—C3126.54 (18)C10—C7—H7A108.9
N1—C2—C3108.00 (15)O3—C8—C9106.96 (17)
C4—C3—C2104.81 (15)O3—C8—H8B110.3
C4—C3—H3B110.8C9—C8—H8B110.3
C2—C3—H3B110.8O3—C8—H8A110.3
C4—C3—H3A110.8C9—C8—H8A110.3
C2—C3—H3A110.8H8B—C8—H8A108.6
H3B—C3—H3A108.9C8—C9—C10103.06 (14)
C3—C4—C5104.93 (12)C8—C9—H9B111.2
C3—C4—H4B110.8C10—C9—H9B111.2
C5—C4—H4B110.8C8—C9—H9A111.2
C3—C4—H4A110.8C10—C9—H9A111.2
C5—C4—H4A110.8H9B—C9—H9A109.1
H4B—C4—H4A108.8C11—C10—C9110.32 (16)
N1—C5—C6108.57 (12)C11—C10—C7111.95 (13)
N1—C5—C4103.15 (13)C9—C10—C7100.16 (14)
C6—C5—C4114.91 (13)C11—C10—H10A111.3
N1—C5—H5A110.0C9—C10—H10A111.3
C6—C5—H5A110.0C7—C10—H10A111.3
C4—C5—H5A110.0N1—C11—C10110.56 (13)
O2—C6—C7108.67 (13)N1—C11—H11B109.5
O2—C6—C5111.18 (13)C10—C11—H11B109.5
C7—C6—C5111.84 (12)N1—C11—H11A109.5
O2—C6—H6A108.4C10—C11—H11A109.5
C7—C6—H6A108.4H11B—C11—H11A108.1
C5—C6—H6A108.4C2—N1—C11124.84 (15)
O3—C7—C6110.87 (13)C2—N1—C5114.01 (14)
O3—C7—C10104.17 (14)C11—N1—C5118.47 (13)
C6—C7—C10114.99 (13)C6—O2—H2A110.8 (18)
O3—C7—H7A108.9C7—O3—C8108.27 (13)
O1—C2—C3—C4−171.33 (18)O3—C7—C10—C941.27 (16)
N1—C2—C3—C49.79 (19)C6—C7—C10—C9162.80 (14)
C2—C3—C4—C5−19.80 (18)C9—C10—C11—N1−156.02 (15)
C3—C4—C5—N122.25 (17)C7—C10—C11—N1−45.4 (2)
C3—C4—C5—C6−95.73 (16)O1—C2—N1—C11−12.7 (3)
N1—C5—C6—O2173.44 (14)C3—C2—N1—C11166.20 (16)
C4—C5—C6—O2−71.68 (18)O1—C2—N1—C5−173.78 (17)
N1—C5—C6—C751.76 (17)C3—C2—N1—C55.11 (19)
C4—C5—C6—C7166.64 (13)C10—C11—N1—C2−105.48 (18)
O2—C6—C7—O3−54.82 (17)C10—C11—N1—C554.8 (2)
C5—C6—C7—O368.30 (16)C6—C5—N1—C2104.77 (16)
O2—C6—C7—C10−172.63 (14)C4—C5—N1—C2−17.57 (17)
C5—C6—C7—C10−49.52 (19)C6—C5—N1—C11−57.6 (2)
O3—C8—C9—C1019.3 (2)C4—C5—N1—C11−179.96 (15)
C8—C9—C10—C1182.07 (18)C6—C7—O3—C8−154.92 (13)
C8—C9—C10—C7−36.05 (18)C10—C7—O3—C8−30.69 (17)
O3—C7—C10—C11−75.64 (18)C9—C8—O3—C77.04 (19)
C6—C7—C10—C1145.9 (2)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
O2—H2A···O3i0.82 (3)2.15 (3)2.9233 (19)157 (2)

Symmetry codes: (i) −x+2, y−1/2, −z+2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BG2263).

References

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