A Concise Total Synthesis of (+)‐Heliotridine

Abstract

A practical synthesis of the necine base (+)‐heliotridine (1) is reported here. The present total synthesis is based on the highly selective 1,3‐dipolar cycloaddition of (S)‐3‐tert‐butoxypyrroline N‐oxide (2) to the commercially available ethyl 4‐bromocrotonate, followed by a suitable elaboration of the adduct. The synthesis gives a 17% overall yield from nitrone 2. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Expedient Pyrrolizidine Synthesis by Propargylsilane Addition toN-Acyliminium Ions followed by Gold-Catalyzed α-Allenyl Amide Cyclization

“…To illustrate the synthetic utility, we applied the sequence of N -acyliminium ion addition and gold-catalyzed cyclization to the synthesis of three pyrrolizidine alkaloids, supinidine 51 , heliotridine 54 , and retronecine 55 (Scheme ). Racemic supinidine was obtained by LiAlH 4 reduction of bicyclic 33 in a yield of 91%.…”

Pyrrolizidine alkaloids

“…Continuing previous work on (À)-rosmarinecine and other, non-natural pyrrolizidines, Brandi and Cordero used a cycloaddition strategy to synthesise (+)-heliotridine from chiral nitrone 351 (Scheme 47), derived from diethyl (S)-malate in ve steps. 135 The 1,3-dipolar cycloaddition with ethyl 4-bromocrotonate proceeded with complete regio-and diastereoselectivity to give the endo-product (not shown) exclusively. N-O reduction, and cyclisation onto the primary bromide was effected in a onepot procedure (step b) to give the pyrrolizidine core (352), then dehydration, ester reduction, and deprotection gave (+)-heliotridine.…”