Synthesis of thiogibberellins: X-ray molecular and crystal structure of 19,10-thio-3-epigibberellin A1

Abstract

The synthesis of thiogibberellins required for studies on structure–biological activity relationships is described. The 7 -thiogibberellin analogues (10), (11), and (13) were prepared via sulphydrolysis of the corresponding symmetric anhydrides (4)–(6). Photolysis of (10) and (13) led, under intramolecular functionalization, to the 7,15_α-thiolactones (15) and (17), respectively. For synthesis of 19,10-thiogibberellins, the Δ¹⁽¹⁰⁾-thiocarboxylic intermediate (22) was prepared in 4 steps from GA₃ methyl ester (18). The regio- and stereo-selective γ-thiolactone ring closure in (22) was achieved by intramolecular photoaddition or upon treatment with hydrogen sulphide–pyridine to give (23). Deacetylation of (23) with sodium methoxide led via simultaneous retro-aldol reaction to the 3α-hydroxylated thiolactone methyl ester (25), which was demethylated to 19,10-thio-3-epi-GA₁(26). The structure of the methyl ester (25) was independently confirmed by X-ray analysis.