(6S,7S,8S,8aS)-6-Ethyl-7,8-dihy­droxy-1,5,6,7,8,8a-hexa­hydro­indolizin-3(2H)-one monohydrate

Viktor Vrábel; Ľubomír Švorc; Peter Šafář; Jozefína Žúžiová

doi:10.1107/S1600536810044855

. 2010 Nov 10;66(Pt 12):o3112–o3113. doi: 10.1107/S1600536810044855

(6S,7S,8S,8aS)-6-Ethyl-7,8-dihydroxy-1,5,6,7,8,8a-hexahydroindolizin-3(2H)-one monohydrate

Viktor Vrábel ^a,^*, Ľubomír Švorc ^a, Peter Šafář ^b, Jozefína Žúžiová ^b

PMCID: PMC3011597 PMID: 21589417

Abstract

The absolute configuration of the title compound, C₁₀H₁₇NO₃·H₂O, was assigned from the synthesis. In the molecular structure, the central six-membered ring of the indolizine moiety adopts a chair conformation, with two atoms displaced by −0.578 (2) and 0.651 (1) Å from the plane of the other four atoms [maximum deviation 0.019 (2) Å] The conformation of the fused oxopyrrolidine ring is close to that of a flat envelope, with the flap atom displaced by 0.294 (1) Å from the plane through the remaining four atoms. In the crystal, one of the hydroxy groups is hydrogen-bonded to two water molecules, while the other hydroxy group exhibits an intermolecular hydrogen bond to the carbonyl O atom, resulting in a chain parallel to the b axis.

Related literature

For the uses of indolizine-based molecules, see: Weidner et al. (1989 ▶); Jaung & Jung (2003 ▶); Rotaru et al. (2005 ▶); Saeva & Luss (1988 ▶); Kelin et al. (2001 ▶). For biological activities of indolizines, see: Oslund et al. (2008 ▶); Asano et al. (2000 ▶); Tielmann & Hoenke (2006 ▶). For synthesis, see: Šafař et al. (2010 ▶). For ring-puckering and conformational analysis, see: Cremer & Pople (1975 ▶); Nardelli (1983 ▶).

Experimental

Crystal data

C₁₀H₁₇NO₃·H₂O
M _r = 217.26
Orthorhombic,
a = 7.1398 (3) Å
b = 7.3169 (2) Å
c = 20.8466 (9) Å
V = 1089.05 (7) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 298 K
0.55 × 0.25 × 0.09 mm

Data collection

Oxford Gemini R CCD diffractometer
Absorption correction: analytical (Clark & Reid, 1995 ▶) T _min = 0.945, T _max = 0.991
17428 measured reflections
1308 independent reflections
1161 reflections with I > 2σ(I)
R _int = 0.028

Refinement

R[F ² > 2σ(F ²)] = 0.029
wR(F ²) = 0.081
S = 1.06
1308 reflections
148 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.16 e Å⁻³
Δρ_min = −0.14 e Å⁻³

Data collection: CrysAlis CCD (Oxford Diffraction, 2006 ▶); cell refinement: CrysAlis RED (Oxford Diffraction, 2006 ▶); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: DIAMOND (Brandenburg, 2001 ▶); software used to prepare material for publication: enCIFer (Allen et al., 2004 ▶) and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810044855/fj2360sup1.cif

e-66-o3112-sup1.cif^{(18KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810044855/fj2360Isup2.hkl

e-66-o3112-Isup2.hkl^{(64.6KB, 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
O22—H22A⋯O21ⁱ	0.82 (3)	1.94 (3)	2.7505 (19)	173 (3)
O24—H24A⋯O22ⁱⁱ	0.91 (3)	2.07 (3)	2.919 (2)	155 (2)
O24—H24B⋯O23ⁱⁱⁱ	0.78 (3)	2.14 (3)	2.907 (2)	167 (3)

Open in a new tab

Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Acknowledgments

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

supplementary crystallographic information

Comment

Indolizines based molecules are known for their use as synthetic dyes (Weidner et al., 1989; Jaung & Jung, 2003), fluorescent materials (Rotaru et al., 2005; Saeva & Luss, 1988) and also as key intermediates for the synthesis of indolizine based molecules (Kelin et al., 2001). Indolizines both synthetic and natural have also been ascribed with a number of useful biological activities (Oslund et al., 2008; Asano et al., 2000; Tielmann & Hoenke, 2006) such as antibacterial, antiviral, CNS depressants, anti-HIV, anti-cancer and have been used for treating cardiovascular ailments.

Due to the diverse properties of indolizine derivatives, the structure of the title compound, (I), has been determined as part of our study of the conformational changes caused by different substituents at various positions on the indolizine ring system. The absolute configuration was established by synthesis and is depicted in the scheme and figure. The expected stereochemistry of atoms C5, C6, C7 and C8 was confirmed as S, S, S and S, 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, C8 and C9 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 -0.578 (2) and 0.651 (1) Å, respectively. The oxopyrrolidine ring attached to the indolizine ring system has flat-envelope conformation with atom C4 on the flap (Nardelli, 1983). The deviation of atom C4 from the mean plane of the remaining four atoms N1/C2/C3/C5 is 0.294 (1) Å. The N1—C5 and N1—C9 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 (358.4 (2)°). These data are consistent with conjugation of the lone-pair electrons on N1 with the adjacent carbonyl C2═O21. The H atoms (H24A and H24B) of the water molecule form O—H···O intermolecular hydrogen bonds with the O atoms (O22 and O23) of both present hydroxy groups, which may, in part, influence the molecular configuration. There have been observed also another intermolecular O—H···O hydrogen bonds, in which carbonyl oxygen O21 participates as acceptor and atom O22 as donator (Table 1). All the interactions demonstrated were found by PLATON (Spek, 2009).

Experimental

The title compound 6S,7S,8S,8aS)-6-ethyl-7,8-dihydroxyhexahydroindolizin-3(2H)-one monohydrate was prepared according literature procedures of Šafař et al. (2010).