| Abstract
| - Stereoselective total syntheses of the racemic form and the natural enantiomer of the tricyclic marinealkaloid lepadiformine (6) have been accomplished using a novel intramolecular spirocyclizationof an N-acyliminium ion with an allylsilane to form the A/C rings as the key step. Introduction ofthe hydroxymethyl group at C-13 of the racemic spirocycle 11 was achieved using our methodologyfor oxidative radical-based remote functionalization of o-aminobenzamides, followed by copper-catalyzed addition of Grignard reagent 16 to the N-acyliminium ion intermediate derived from 15.Subsequent Tamao oxidation of silane 17 then afforded the requisite hydroxymethyl compound19, which was converted to the dimethyl acetal 25 via hydroformylation followed by aldehydeprotection. Hydrolysis of the benzamide moiety of 25 and subsequent protection of the primaryalcohol gave amino acetal 27. The synthesis was concluded from 27 by a four-step procedure: acid-catalyzed ring closure, amino nitrile formation, introduction of the hexyl chain by a Grignard reactionto an iminium salt, and removal of the O-benzyl protecting group to give (±)-lepadiformine (6).The enantioselective total synthesis of 6 started from known optically pure bromide 37, derivedfrom (S)-pyroglutamic acid, and followed a similar sequence involving the key spirocyclization ofN-acyliminium ion 42. This synthesis has established the absolute configuration of naturallyoccurring lepadiformine to be 2(R),5(S),10(S),13(S).
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