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

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 CH3OH/CH2Cl2/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,7S) or (aR,7S) instead of (aS,7S).