Covalent reversible binding of alkoxides or thiolates to colchicinoids

Abstract

¹ H NMR spectroscopic monitoring in 28:1 (CD₃)₂SO–CD₃OD at room temp, shows that colchicine 1a reacts extensively with equimolar NaOCD₃ giving reversibly the σ-adduct 2a, via CD₃O^– addition at C-10, as proved by similar experiments with [8,11-²H₂]colchicine 1b, in which 2b was obtained. Under similar conditions, dithiocolchicine 1d also reacts extensively with equimolar NaSMe via MeS^– addition at C-10 to give adduct 4. In contrast, isocolchicine 8 and equimolar NaOCD₃ give only very little σ-adduct (of alternative structure 9 or 10) whereas in the case of thiocolchicine 1c and equimolar NaSEt only broadening of ring-C ¹H NMR signals, most markedly of 11-H, was observed, indicating rapid exchange at C-10. It is concluded that, among a few analogies, the behaviour of colchicinoids toward bases differs sharply from that of troponoids.