Synthesis of ambrox and its derivatives from nidorellol

Abstract

Herein synthesis of (+)-ambrox from (−)-nidorellol is reported. The key reaction in the synthesis involved acid-promoted cyclization of (−)-nidorellol, ozonolysis of the acid-promoted cyclized products and dehydroxylation of the 7-hydroxyl group. (+)-Ambrox has been obtained by a seven-step procedure in 53% overall yield from (−)-nidorellol. Since the ambrox synthesis from (−)-nidorellol gave (+)-ambrox, an ent-ambrox configuration, instead of the expected product, (−)-ambrox, the absolute configuration of (−)-nidorellol has thus been shown to be opposite to that illustrated in previous report. Therefore, the correct absolute configuration of (−)-nidorellol has been proved to be trans-(5R,7R,8R,9S,10R)-labda-12,14-diene-7α,8β-diol. In addition fixative property of (−)-nidorellol, (+)-ambrox and its derivatives were examined by smelling paper strip test and profiles of thermal gravimetric analysis (TGA) and (−)-ambrox was used as positive control. (−)-Nidorellol and (−)-ambrox exhibited fixative property while (+)-ambrox and its derivatives, did not show fixative property.