30 TOTAL SYNTHESIS OF ERGOT ALKALOIDS HAVING AN ERGOLINE NUCLEUS

Kiguchi T., Hashimoto C., Naito T., Ninomiya I.

doi:10.24496/tennenyuki.27.0_222

According to the strategy of synthesizing all members of one group of alkaloids by one methodology, we have successfully applied reductive photocyclization of N-furoylenamines to the synthesis of ergoline group of alkaloids. Reductive photocyclization of the N-furoylenamines (2a, b) afforded the C/D-trans-lactams (3a, b) and cis-lactams (4a, b) respectively. Cleavage of the dihydrofuran ring of these lactams was performed by two routes to afford useful key compounds, 1,3-diols (8) and (10-12). Constructions of the ring D-structures characteristic to respective alkaloids were accomplished as follows. Regioselective dehydration of 9α-hydroxy group in the synthetic intermediates (15, 16, 19, and 22) with thionyl chloride afforded the 8-ergolenes (24, 27, and 29) and the 9-ergolenes (21, 25, and 28) respectively. Inversion of 9α-hydroxy group of the monomesylate (30) with potassium superoxide and double elimination of the dimesylates (32 and 33) with potassium t-butoxide gave the indolines (31 and 34) respectively. A convenient procedure for dehydrogenation of indolines into indoles by the reaction with phenylseleninic anhydride in the presence of indole was developed and successfully applied to the final steps in total synthesis of eight ergot alkaloids, lysergol, isolysergol, elymoclavine, isolysergine, agroclavine, agroclavine-I, fumigaclavine B, and lysergene, as racemates, with 80-97% yields.

30 TOTAL SYNTHESIS OF ERGOT ALKALOIDS HAVING AN ERGOLINE NUCLEUS

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