Synthesis and crystal structure of 17-deaza-17-methyl thionium isomorphinan (isosulforphanol) perchlorate, an isostere of the opiate isolevorphanolBernard Belleau, Ugo Gulini, Barbara Gour-Salin, F. R. AhmedCan. J. Chem. 63, 1268 (1985)
(
https://www.thevespiary.org/rhodium/Rhodium/pdf/isosulforphanol.pdf)
AbstractNo morphinan analog carrying a heteroatom other than nitrogen at position 17 has yet been synthesized. The synthesis of the position 17 sulfur analog of the perchlorate salt of (±)-isolevorphanol is described. The strategy adopted is based on the classical Grewe synthesis of morphinans and, under narrowly defined conditions, the title compound isosulforphanol (
3a) and an intermediate by-product 13 resulting from an unusual non-bridged head ring closure of
11a were obtained. The X-ray structures of both 3a and 13 were determined. Crystals of
13 are monoclinic. The crystals of 3a are orthorhombic. The C
17H
23OS
+ molecule has been identified by this X-ray analysis as S-methyl isosulforphanol (Fig. 2). The structure of
13 is shown in Fig. 1. The stereochemical outcome of the Grewe-like synthesis is thus established as proceeding in a reversed manner when sulfur replaces the nitrogen in the final cyclization step. Preliminary pharmacological studies showed that
3a is a potent agonist in the central nervous system but a potent antagonist on the guinea-pig ileum.
