Conversion of N-hydroxytryptophan into α-functionalised tryptophans. An approach to the sporidesmin series

Abstract

Reaction of the N-hydroxytryptophan derivative (5a) with pyruvoyl chloride gives access to the N-hydroxypiperazines (6a) and (13). O-Alkylation of the latter compounds, followed by base treatment in the presence or absence of methanol, affords the dioxopiperazines (7a) and (20), respectively. Subsequent oxidative ring closure using singlet oxygen yields the corresponding tetracyclic compounds (8a) and (25)–(29). The compounds (25) and (8a) having the skeleton and stereochemistry of the spirodesmins (1a–c) can be separated from their stereoisomers (26) and (27), respectively, by column chromatography. They are potential precursors of the fungal metabolites. Until now, attempts to replace the C-11 a methoxy group of (25) and (8a) by a sulphur substituent have failed.

Finally, the properly substituted N-hydroxytryptophan derivative (5b) has been prepared by cycloaddition of (2b) with the nitroso olefin (3), followed by aminolysis of the addition product and subsequent selective reduction of the oxime function.