Redetermined structure of oxaline: absolute configuration using Cu Kα radiation

Peng Qu; Zhi-Yong Wu; Wei-Ming Zhu

doi:10.1107/S1600536812019423

. 2012 May 5;68(Pt 6):o1626. doi: 10.1107/S1600536812019423

Redetermined structure of oxaline: absolute configuration using Cu Kα radiation

Peng Qu ^a, Zhi-Yong Wu ^a, Wei-Ming Zhu ^a,^*

PMCID: PMC3379231 PMID: 22719429

Abstract

In the title compound, C₂₄H₂₅N₅O₄, the stereogenic C atom bonded to three N atoms and one C atom has an S configuration and its directly bonded neighbour has an R configuration. An intramolecular N—H⋯O hydrogen bond supports the near coplanarity of the two C₃N₂-five-membered rings [dihedral angle = 5.64 (10)°]. In the crystal, molecules are linked by N—H⋯N hydrogen bonds, forming a C(8) chain propagating in [001]. The chains are connected by C—H⋯O interactions, generating a three-dimensional network. The previous study [Nagel et al. (1974 ▶). Chem. Commun. pp. 1021–1022] did not establish the absolute structure and no atomic coordinates were published or deposited.

Related literature

For the previous structure, see: Nagel et al. (1974 ▶). For background to oxaline and its properties, see: Steyn (1970 ▶); Koizumi et al. (2004 ▶). For puckering parameters, see: Cremer & Pople (1975 ▶). graphic file with name e-68-o1626-scheme1.jpg

Experimental

Crystal data

C₂₄H₂₅N₅O₄
M _r = 447.49
Orthorhombic,
a = 10.7897 (2) Å
b = 13.2457 (3) Å
c = 15.6436 (4) Å
V = 2235.74 (9) Å³
Z = 4
Cu Kα radiation
μ = 0.76 mm⁻¹
T = 100 K
0.60 × 0.20 × 0.12 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2003 ▶) T _min = 0.658, T _max = 0.914
11202 measured reflections
3786 independent reflections
3766 reflections with I > 2σ(I)
R _int = 0.034

Refinement

R[F ² > 2σ(F ²)] = 0.035
wR(F ²) = 0.089
S = 1.08
3786 reflections
379 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.64 e Å⁻³
Δρ_min = −0.26 e Å⁻³
Absolute structure: Flack (1983 ▶), 1403 Friedel pairs
Flack parameter: −0.05 (18)

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: SAINT (Bruker, 2004 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: XP in SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812019423/hb6738sup1.cif

e-68-o1626-sup1.cif^{(25.3KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812019423/hb6738Isup2.hkl

e-68-o1626-Isup2.hkl^{(181.9KB, 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
N17—H17⋯O13	0.89 (2)	1.85 (2)	2.6562 (19)	151 (2)
N14—H14⋯N19ⁱ	0.83 (2)	1.97 (2)	2.798 (2)	175 (2)
C4—H4⋯O9ⁱⁱ	0.97 (2)	2.54 (2)	3.154 (2)	121.5 (16)
C20—H20⋯O13ⁱⁱⁱ	1.00 (2)	2.54 (2)	3.353 (2)	137.9 (16)
C24—H24C⋯O13^iv	0.98 (3)	2.47 (3)	3.382 (2)	154 (2)

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

Acknowledgments

This work was supported by grants from the NSFC (No. 21172204), the Special Fund for Marine Scientific Research in the Public Interest of China (No. 2010418022–3) and the PCSIRT (No. IRT0944).

supplementary crystallographic information

Comment

Oxaline is a member of a class of biologically active indole alkaloids, characterized by a unique indoline spiroaminal framework and substitution of a 1,1-dimethylallyl ("reverse-prenyl") group at the benzylic ring junction. Oxaline was originally isolated from the culture broth of Penicillium oxalicum HK14–01 containing several unique structural features, including the N-OMe group, the unusual coupling of tryptophan and histidine, a single carbon atom bearing three nitrogen functionalities and a reversed prenyl group (Steyn, 1970). Besides, oxaline was found to inhibit tubulin polymerization in Jarkat cells, resulting in cell cycle arrest at the M phase (Koizumi et al., 2004). The X-ray structure of oxaline on Mo—Kα data was determined without definite absolute configuration (Nagel, et al., 1974). We isolated oxaline as part of our ongoing studies on characterizing bioactive metabolites from marine-derived halotolerant fungi. And the crystal structure on Cu—Kα and the absolute configuration are reported here.

The title compound I contains a four fused rings structure as illustrated in Fig. 1. Two chiral atoms of C2 and C3 have the absolute configurations of S and R, respectively. Atom of N1 is S but it can invert in solution. Atom O1 in I (S-) has a short intra-contact of O1···N14 [2.7018 (19) Å]. While in R- one, the short contact are 2.882(C3), 2.581(C8), 2.390(C9), 2.662(C10) and 2.675 Å(N11), which indicates a unfavorable configuration. Both bonds of C8═C9 and C12═C15 are E but cis conformation. The five-membered ring of N1—C2—C3—C3A—C7A adopts envelope conformation with the puckering parameters (Cremer and Pople, 1975) of Q[0.3968 (17) Å] and φ[34.8 (2)°]. The six-membered ring of C2—C3—C8—C9—C10—N11 has the puckering parameters of Q = 0.4342 (17) Å, θ = 69.0 (2)° and φ = 76.8 (2)°, which implies a conformation among boat, twist-boat and half-chair.

In the crystal, there are a one-dimensional classical hydrogen bonding chain parallel to the c axis (Fig. 2, Table 2) and a non-classical one along the b axis. These two kinds of chains together weave a three-dimensional supramolecular structure (Fig. 3).

Experimental

The halotolerant fugal strain Penicillium chrysogenum HK14–01, was isolated from the sediments collected in the Yellow River Delta, Dongying, Shandong, China. The working strain was cultured under static conditions at 298 K for 35 days in two hundred 1L conical flasks containing the liquid medium (300 ml/flask) composed of glucose (10 g/L), peptone (5 g/L), yeast extract (3 g/L), malt extract (1.5 g/L), marinum salt (100 g/L). The fermented whole broth (60 L) was filtered through cheese cloth to separate into supernatant and mycelia. The mycelia was extracted three times with acetone. The acetone solution was concentrated under reduced pressure to afford an aqueous solution. The acetone solution was extracted three times with ethyl acetate to give an ethyl acetate solution which was concentrated under reduced pressure to give a crude extract (39 g). The crude extract, which was subjected to chromatography over silica gel column using a stepwise gradient elution of CH₂Cl₂/petroleum ether(50–100%,V/V) and CH₂Cl₂/MeOH (0–100%,V/V),to yield twelve fractions (Fr.1-Fr.12). Fr.9, was fractionated on a C-18 ODS column using a step gradient elution of MeOH/H₂O (60–100%,V/V) and was separated into 6 subfractions (Fr.9.1-Fr.9.6). Fr.9.3 was applied on Sephadex LH-20 using CH₂Cl₂/MeOH (1:1) to yield the title compound (145.0 mg). Colourless blocks were obtained by slow evaporation of petroleum ether/acetone (1:1) solution at 298 K.