SYNTHESES OF TREHAZOLIN, TREHALAMINE, AND THE AMINOCYCLITOL MOIETY OF TREHAZOLIN - DETERMINATION OF ABSOLUTE-CONFIGURATION OF TREHAZOLIN

The syntheses and determination of the absolute configurations of trehazolin (1), its aglycon (trehalamine (3)), and its aminocyclitol hexaacetate moiety (5) are described. An important intermediate, optically active epoxide 16 alpha, was obtained from an 11-step synthesis starting from D-glucose. The route has [3+2] cycloaddition and Sharpless epoxidation reactions as the key steps. Trehazolin and trehalamine were subsequently synthesized from 16 alpha, utilizing 2-chloro-3-ethyl-benzoxazolium tetrafluoroborate to construct aminooxazoline frameworks via the carbodiimide derivatives 30 and 27 derived from thioureas 29 and 26, respectively. The absolute configurations of the trehazolin aglycon and aminocyclitol moieties were determined to be [3aR-(3a alpha,4 alpha,5 beta,6 alpha,6a alpha)] and [1R-(1 alpha,2 beta,3 alpha,4 beta,5 beta)], respectively. Alternatively, the synthesis of trehazolin could be completed through nonprotected aminocyclitol 32, which was obtainable from deprotection of compound 5 or degradation of natural trehazolin.