Dihydrocolchicine 8,12‐Endoperoxide: A Novel Starting Material for Convenient Syntheses of the Allocolchicinoids <i>N</i>‐Acetylcolchinol <i>O</i>‐Methyl Ether and Androbiphenyline

Abstract

Abstract Optically pure dihydrocolchicine‐8,12‐endoperoxide 2 is used as the starting material for the synthesis of some bioactive allocolchicinoids. Depending on the reaction conditions and reagents employed, different modifications of the C ring of colchicine ( 1 ) are achieved. Triphenylphosphane deoxygenation of 2 leads to the well known N ‐acetylcolchinol O ‐methyl ether (NCME, 6 , 40% yield from 1 ). Treatment of the endoperoxide 2 with CH 3 OH/CH 2 Cl 2 /silica gel provides the plant alkaloid androbiphenyline ( 11 ) in a yield of 60% from 1 . Triethylamine‐catalysed transformation of 2 yields (−)‐colchicine‐8,12‐dione ( 12 ) (17% yield), together with a mixture of interconverting tetracyclic hemiketals 8a and 8b . For the formation of the allo colchicinoids 6 and 11 plausible reaction pathways are suggested. In contrast to what is found in the literature, the assignment of the absolute configuration of natural (−)‐colchicine ( 1 ), and the allo‐congeners 6 and 11 , should be ( M ,7 S ) or (a R ,7 S ) instead of (a S ,7 S ).