Synthetic studies on (S,S)-isodityrosine and biotin derivative

Abstract

A new stereoselective synthesis of (S,S)-isodityrosine 1 featuring bisaziridination as a key step was attempted. Bisolefin 43 was obtained via Ullmann coupling with olefin 47 and 48, and but 42 was provideded by Baeyer-Villiger oxidation of 43. But aziridination of 43 or 42 did not occur. Aziridination of olefin 47 and 51 was performed prior to biaryl ether formation, but conversion was not satisfactory. Alternatively, carbene addition to the diimine 61 was attempted, but the desired bisaziridine 60 was not furnished. Opening of aziridine 66b by organocuprate derived from 65 was performed. However, no promising result was found. Synthesis of biotin derivative 34 was studied. Our first attempts to construct amide linkage prior to carbamate formation were unsuccessful. Reaction of biotin benzyl ester 74 and chloroformate 76 afforded carbamate 77, of which hydrogenolysis is in progress.