Optically active 3-amino-2H-azirines as synthons for enantiomerically pure alpha,alpha-disubstituted alpha-amino acids: Syntheses of isovaline synthons and a segment of Trichotoxin A-50

The synthesis of a novel 3-amino-2-methyl-2-[2-(phenylsulfonyl)ethyl]-2H-azirine derivative 12 with a chiral substituent at the amino group is described. Chromatographic separation of the diastereoisomer mixture gave pure diastereoisomers which, after an electrochemical cleavage of the phenylsulfonyl group, yielded the (S)- and (R)-isovalin (Iva) synthons 13a and 13b, respectively. The absolute configuration of the precursor molecule 12b was established by X-ray crystallography. The Iva synthons were successfully used in the synthesis of the C-terminal pentapeptide Z-Leu-Aib-(R)-Iva-Gln-Valoi of the peptaibole Trichotoxin A-50 and its epimer.