Original scientific paper

Chemistry of 1,3-Dioxepins. XV.1 Syntheses and Structure of Nitroaryl Analogues of Antihyperglycaemic N-Sulphonyl-1a,2,6,6a-tetrahydro-1H,4H-[1,3]-dioxepino[5,6-b]azirines

Marina Orešić ; PLIVA d.d., Research and Development, Prilaz baruna Filipovića 25, 10000 Zagreb, Croatia
Darko Filić ; PLIVA d.d., Research and Development, Prilaz baruna Filipovića 25, 10000 Zagreb, Croatia
Biserka Prugovečki ; Laboratory of General and Inorganic Chemistry, Faculty of Science, University of Zagreb, Kralja Zvonimira 8, 10000 Zagreb, Croatia
Mladen Vinković ; PLIVA d.d., Research and Development, Prilaz baruna Filipovića 25, 10000 Zagreb, Croatia
Miljenko Dumić ; PLIVA d.d., Research and Development, Prilaz baruna Filipovića 25, 10000 Zagreb, Croatia

Abstract

Regio and stereocontrolled syntheses of novel nitrophenyl analogues of antihyperglycaemic N-sulphonyl-1a,2,6,6a-tetrahydro-1H,4H-[1,3]-dioxepino[5,6-b]azirines: N-nitrobenzenesulphonylcyclohepta[6]azirine 6, N-nitrobenzenesulphonyldioxepinoazirines 7-10, N-nitro-benzoyldioxepinoazirine 11 and N-nitrobenzyldioxepinoazirine 12, starting from cycloheptene (2), trans-6-acetylamino-2-isopropyl-5-chloro-1,3-dioxepane (13) and 5,6-epoxy-1,3-dioxepane (14), are described. Their crystallographic data show that: (a) boat-chair (BC) conformation of dioxepinoazirine and cyclohepta[b]azirine moieties dominates; (b) the substituent on aziridine nitrogen is always in trans and never in cis position in relation to the cycloheptane or dioxepane ring; (c) the sulphonyl group of sulphonylaziridines 6 and 8-10 adopts only one of the two possible conformations in relation to the aziridine ring, with torsion angles C1-S-N-C7 of ≅ 80° (corresponding angle O1-S-N-LP ≅ 180°, LP = lone pair) named by us conformation BC*; (d) orientation of the analogous carbonyl group of 11 and methylene group of 12 is defined by torsion angles C1-C0-N1-C7 of -78.3 (9)° and -93.9 (5)° respectively; (e) nitrogen atom in all studied N-sulphonyl-, acyl- and alkyl- aziridines is sp3 hybridised, in contrast to other sulphonamides where sp2 hybridisation is predominant; (f) nitrogen atom in alkylaziridine 12 is more pyramidal in relation to N-sulphonyl and N-acyl derivatives, and according to torsion angles 05-N2-C4-C5, the nitro group in all studied compounds is approximately coplanar to the phenyl ring plane. Obtained data will serve for further investigation of steric and electronic properties of studied compounds aimed at designing more antihyperglycaemically potent analogues.

Keywords

1,3-dioxepins; antihyperglycaemic activity; N-sulphonyl-1a,2,6,6a-tetrahydro-1H,4H-[1,3]dioxepino[5,6-b]azirines; nitroaryl analogues; regio and stereocontrolled syntheses

Hrčak ID:

131899

URI

https://hrcak.srce.hr/131899

Publication date:

1.8.2001.

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