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

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.

Key indicators

• Single-crystal X-ray study
• T = 298 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.029
• wR factor = 0.081
• Data-to-parameter ratio = 8.8

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT910_ALERT_3_C Missing # of FCF Reflections Below Th(Min) .....          8
PLAT790_ALERT_4_C Centre of Gravity not Within Unit Cell: Resd.  #          2
              H2 O

Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           26.37
           From the CIF: _reflns_number_total               1308
           Count of symmetry unique reflns         1316
           Completeness (_total/calc)             99.39%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured         0
           Fraction of Friedel pairs measured     0.000
           Are heavy atom types Z>Si present         no
PLAT791_ALERT_4_G Note: The Model has Chirality at C5     (Verify)          S
PLAT791_ALERT_4_G Note: The Model has Chirality at C6     (Verify)          S
PLAT791_ALERT_4_G Note: The Model has Chirality at C7     (Verify)          S
PLAT791_ALERT_4_G Note: The Model has Chirality at C8     (Verify)          S
PLAT981_ALERT_1_G No non-zero f" Anomalous Scattering Values Found          ?

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   2 ALERT level C = Check and explain
   6 ALERT level G = General alerts; check

   1 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   1 ALERT type 3 Indicator that the structure quality may be low
   6 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

---

S1. 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).

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). For software used to analyse hydrogen bonds, see: Spek (2009). [Please check amended text]

S2. 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).

S3. Refinement

All H atoms were placed in geometrically idealized positions and constrained to ride on their parent atoms, with C—H distances in the range 0.93–0.98 Å and O—H distance 0.85 Å and U_iso set at 1.2U_eq 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; 907 total Friedel pairs have been merged. Due to the absence of anomalous dispersion the Flack parameter was not refined

Computing details

Data collection: CrysAlis CCD (Oxford Diffraction, 2006); cell refinement: CrysAlis RED (Oxford Diffraction, 2006); data reduction: CrysAlis RED (Oxford Diffraction, 2006); 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).

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. A packing of the molecule of (I), viewed along the b axis.

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

Crystal data

C10H17NO3·H2O	F(000) = 472
Mr = 217.26	Dx = 1.325 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 10421 reflections
a = 7.1398 (3) Å	θ = 3.4–29.5°
b = 7.3169 (2) Å	µ = 0.10 mm^−1
c = 20.8466 (9) Å	T = 298 K
V = 1089.05 (7) Å^3	Prism, colourless
Z = 4	0.55 × 0.25 × 0.09 mm

Data collection

Oxford Gemini R CCD diffractometer	1308 independent reflections
Radiation source: fine-focus sealed tube	1161 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.028
Detector resolution: 10.4340 pixels mm^-1	θmax = 26.4°, θmin = 4.1°
Rotation method data acquisition using ω and φ scans	h = −8→8
Absorption correction: analytical (Clark & Reid, 1995)	k = −9→9
Tmin = 0.945, Tmax = 0.991	l = −26→26
17428 measured reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.029	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.081	H atoms treated by a mixture of independent and constrained refinement
S = 1.06	w = 1/[σ^2(Fo^2) + (0.0511P)^2 + 0.0923P] where P = (Fo^2 + 2Fc^2)/3
1308 reflections	(Δ/σ)max < 0.001
148 parameters	Δρmax = 0.16 e Å^−3
0 restraints	Δρmin = −0.14 e Å^−3

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 (Ų)

	x	y	z	Uiso*/Ueq
C2	0.7971 (2)	0.5950 (2)	0.21098 (8)	0.0301 (4)
C3	0.7338 (3)	0.7182 (2)	0.26470 (8)	0.0347 (4)
H3B	0.8405	0.7649	0.2884	0.042*
H3A	0.6524	0.6529	0.2941	0.042*
C4	0.6288 (3)	0.8728 (3)	0.23202 (9)	0.0454 (5)
H4B	0.6617	0.9895	0.2510	0.054*
H4A	0.4946	0.8553	0.2358	0.054*
C5	0.6903 (2)	0.8652 (2)	0.16126 (8)	0.0314 (4)
H5A	0.5790	0.8736	0.1339	0.038*
C6	0.8300 (3)	1.0102 (2)	0.14059 (8)	0.0331 (4)
H6A	0.9284	1.0227	0.1731	0.040*
C7	0.9168 (3)	0.9620 (2)	0.07610 (9)	0.0359 (4)
H7A	0.8175	0.9664	0.0437	0.043*
C8	1.0011 (2)	0.7695 (3)	0.07524 (8)	0.0341 (4)
H8A	1.0387	0.7430	0.0310	0.041*
C9	0.8502 (3)	0.6316 (2)	0.09368 (8)	0.0339 (4)
H9B	0.7529	0.6298	0.0612	0.041*
H9A	0.9043	0.5102	0.0963	0.041*
C10	1.1765 (3)	0.7517 (3)	0.11756 (10)	0.0399 (4)
H10B	1.2577	0.8557	0.1098	0.048*
H10A	1.1390	0.7552	0.1623	0.048*
C11	1.2854 (3)	0.5778 (3)	0.10545 (10)	0.0514 (5)
H11C	1.3930	0.5743	0.1331	0.062*
H11B	1.3255	0.5745	0.0615	0.062*
H11A	1.2070	0.4741	0.1141	0.062*
N1	0.7703 (2)	0.68207 (18)	0.15522 (7)	0.0292 (3)
O21	0.8643 (2)	0.44131 (16)	0.21682 (6)	0.0420 (3)
O22	0.7283 (2)	1.17774 (17)	0.13508 (8)	0.0473 (4)
H22A	0.776 (4)	1.257 (4)	0.1571 (12)	0.057*
O23	1.0557 (2)	1.0928 (2)	0.05882 (8)	0.0565 (4)
H23A	1.015 (4)	1.177 (4)	0.0304 (13)	0.068*
O24	0.9507 (2)	1.3468 (3)	−0.03262 (8)	0.0559 (4)
H24A	1.013 (4)	1.312 (4)	−0.0684 (13)	0.067*
H24B	0.851 (4)	1.369 (4)	−0.0451 (13)	0.067*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C2	0.0274 (8)	0.0256 (8)	0.0373 (9)	−0.0042 (7)	−0.0022 (7)	−0.0007 (7)
C3	0.0365 (9)	0.0329 (8)	0.0346 (9)	−0.0024 (8)	0.0014 (7)	−0.0006 (7)
C4	0.0523 (11)	0.0395 (10)	0.0444 (11)	0.0134 (10)	0.0139 (9)	0.0010 (9)
C5	0.0312 (8)	0.0270 (8)	0.0359 (9)	0.0044 (7)	−0.0026 (7)	−0.0004 (7)
C6	0.0355 (9)	0.0251 (8)	0.0387 (9)	−0.0008 (8)	−0.0106 (7)	0.0016 (7)
C7	0.0325 (9)	0.0376 (9)	0.0375 (9)	−0.0057 (8)	−0.0061 (8)	0.0108 (8)
C8	0.0354 (9)	0.0404 (9)	0.0265 (8)	−0.0020 (8)	0.0011 (7)	0.0010 (7)
C9	0.0378 (9)	0.0327 (9)	0.0312 (9)	−0.0021 (8)	0.0004 (7)	−0.0064 (7)
C10	0.0323 (9)	0.0396 (10)	0.0478 (11)	−0.0019 (9)	−0.0005 (8)	0.0035 (9)
C11	0.0504 (12)	0.0576 (13)	0.0462 (12)	0.0150 (11)	−0.0002 (10)	0.0036 (10)
N1	0.0316 (7)	0.0230 (6)	0.0330 (7)	0.0003 (6)	0.0019 (6)	−0.0007 (6)
O21	0.0514 (8)	0.0282 (6)	0.0465 (7)	0.0091 (6)	−0.0047 (7)	0.0021 (6)
O22	0.0560 (9)	0.0234 (6)	0.0624 (9)	0.0034 (7)	−0.0181 (7)	−0.0010 (6)
O23	0.0418 (8)	0.0553 (9)	0.0726 (10)	−0.0098 (8)	−0.0016 (7)	0.0328 (8)
O24	0.0482 (9)	0.0650 (10)	0.0546 (9)	0.0009 (9)	0.0021 (7)	0.0157 (8)

Geometric parameters (Å, º)

C2—O21	1.228 (2)	C7—H7A	0.9800
C2—N1	1.339 (2)	C8—C9	1.525 (2)
C2—C3	1.507 (2)	C8—C10	1.538 (3)
C3—C4	1.518 (3)	C8—H8A	0.9800
C3—H3B	0.9700	C9—N1	1.452 (2)
C3—H3A	0.9700	C9—H9B	0.9700
C4—C5	1.540 (2)	C9—H9A	0.9700
C4—H4B	0.9700	C10—C11	1.513 (3)
C4—H4A	0.9700	C10—H10B	0.9700
C5—N1	1.462 (2)	C10—H10A	0.9700
C5—C6	1.519 (2)	C11—H11C	0.9600
C5—H5A	0.9800	C11—H11B	0.9600
C6—O22	1.429 (2)	C11—H11A	0.9600
C6—C7	1.522 (3)	O22—H22A	0.82 (3)
C6—H6A	0.9800	O23—H23A	0.90 (3)
C7—O23	1.425 (2)	O24—H24A	0.91 (3)
C7—C8	1.532 (3)	O24—H24B	0.78 (3)
O21—C2—N1	125.27 (16)	C8—C7—H7A	107.9
O21—C2—C3	126.23 (16)	C9—C8—C7	109.13 (14)
N1—C2—C3	108.50 (14)	C9—C8—C10	112.01 (14)
C2—C3—C4	105.09 (15)	C7—C8—C10	113.01 (15)
C2—C3—H3B	110.7	C9—C8—H8A	107.5
C4—C3—H3B	110.7	C7—C8—H8A	107.5
C2—C3—H3A	110.7	C10—C8—H8A	107.5
C4—C3—H3A	110.7	N1—C9—C8	109.40 (14)
H3B—C3—H3A	108.8	N1—C9—H9B	109.8
C3—C4—C5	105.20 (14)	C8—C9—H9B	109.8
C3—C4—H4B	110.7	N1—C9—H9A	109.8
C5—C4—H4B	110.7	C8—C9—H9A	109.8
C3—C4—H4A	110.7	H9B—C9—H9A	108.2
C5—C4—H4A	110.7	C11—C10—C8	113.21 (17)
H4B—C4—H4A	108.8	C11—C10—H10B	108.9
N1—C5—C6	111.06 (13)	C8—C10—H10B	108.9
N1—C5—C4	103.10 (13)	C11—C10—H10A	108.9
C6—C5—C4	115.70 (15)	C8—C10—H10A	108.9
N1—C5—H5A	108.9	H10B—C10—H10A	107.7
C6—C5—H5A	108.9	C10—C11—H11C	109.5
C4—C5—H5A	108.9	C10—C11—H11B	109.5
O22—C6—C5	106.74 (14)	H11C—C11—H11B	109.5
O22—C6—C7	109.57 (15)	C10—C11—H11A	109.5
C5—C6—C7	110.85 (14)	H11C—C11—H11A	109.5
O22—C6—H6A	109.9	H11B—C11—H11A	109.5
C5—C6—H6A	109.9	C2—N1—C9	126.13 (14)
C7—C6—H6A	109.9	C2—N1—C5	114.67 (13)
O23—C7—C6	110.54 (16)	C9—N1—C5	117.56 (13)
O23—C7—C8	109.97 (14)	C6—O22—H22A	110.7 (18)
C6—C7—C8	112.57 (14)	C7—O23—H23A	113.7 (16)
O23—C7—H7A	107.9	H24A—O24—H24B	104 (3)
C6—C7—H7A	107.9
O21—C2—C3—C4	−169.29 (17)	C6—C7—C8—C10	−68.92 (19)
N1—C2—C3—C4	11.57 (19)	C7—C8—C9—N1	−55.28 (18)
C2—C3—C4—C5	−17.83 (19)	C10—C8—C9—N1	70.64 (19)
C3—C4—C5—N1	17.48 (19)	C9—C8—C10—C11	69.5 (2)
C3—C4—C5—C6	−103.96 (16)	C7—C8—C10—C11	−166.77 (16)
N1—C5—C6—O22	167.96 (14)	O21—C2—N1—C9	−14.3 (3)
C4—C5—C6—O22	−74.98 (18)	C3—C2—N1—C9	164.90 (15)
N1—C5—C6—C7	48.69 (18)	O21—C2—N1—C5	−179.17 (16)
C4—C5—C6—C7	165.76 (15)	C3—C2—N1—C5	−0.02 (19)
O22—C6—C7—O23	65.90 (18)	C8—C9—N1—C2	−108.10 (19)
C5—C6—C7—O23	−176.56 (14)	C8—C9—N1—C5	56.43 (19)
O22—C6—C7—C8	−170.69 (13)	C6—C5—N1—C2	113.25 (16)
C5—C6—C7—C8	−53.14 (19)	C4—C5—N1—C2	−11.28 (19)
O23—C7—C8—C9	−179.85 (15)	C6—C5—N1—C9	−53.04 (19)
C6—C7—C8—C9	56.42 (18)	C4—C5—N1—C9	−177.56 (15)
O23—C7—C8—C10	54.81 (19)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O22—H22A···O21^i	0.82 (3)	1.94 (3)	2.7505 (19)	173 (3)
O24—H24A···O22^ii	0.91 (3)	2.07 (3)	2.919 (2)	155 (2)
O24—H24B···O23^iii	0.78 (3)	2.14 (3)	2.907 (2)	167 (3)

Symmetry codes: (i) x, y+1, z; (ii) x+1/2, −y+5/2, −z; (iii) x−1/2, −y+5/2, −z.