Synthesis and stereochemistry of stereoisomeric 1,2,3-oxathiazino[4,3-a]isoquinolines

Abstract

The ring-closures of homocalycotomine and its 1′- and 2′-methyl-substituted diastereomers 3, 4 and 7, 8 with thionyl chloride or with sulfuryl chloride led to 1,2,3-oxathiazino[4,3-a]isoquinoline derivatives 9–11 and 18, 19 or to 15, 17 and 22, 23, respectively. The relative configurations and the predominant conformations of the cis¹–trans–cis² conformational equilibrium were studied by means of ¹H- and ¹³C-NMR spectroscopy, with the application of DNOE, 2D HSC and 2D-COSY measurements. In good agreement with the liquid-phase results, the X-ray investigations revealed that 9 and 10 have the cis¹, while 18 has the trans-anellated stereostructure.