環状N, O-アセタールを利用するアルカロイド合成

抄録

Synthesis and reaction of cyclic N, O-acetals can be of potential use and versatility in construction of polycyclic nitrogen heterocycles and alkaloid synthesis, as demonstrated in this review. The cyclic N-acyl-N, O-acetals, readily accessible by condensation of hydroxy-amines with ketocarboxylic acids, was transformed into the 2-azaspirocycles via intramolecular olefin-iminium cyclization mediated by TiCl₄. Construction of the 6, 6-disubstituted 2-piperidone based on Lewis acid-mediated allylation of the cyclic N-acyl-N, O-acetals with allyltrimethylsilane led to a ladybird alkaloid adalinine in racemic form. This allylation reaction was performed with the cyclic N-acyl-N, O-acetal incorporating (R) -2- (1-aminoethyl) phenol as a chiral auxiliary to afford the (R) -6, 6-disubstituted 2-piperidone with high diastereoselectivity, which, on cleavage of the chiral auxiliary, provided (-) -adalinine. The enantioselective Lewis acid-mediated allylation of the cyclic N-acyl-N, O-acetals developed herein was successfully applied to the asymmetric syntheses of Dendrobatid alkaloids (-) -indolizidine 195B and 209D, and marine alkaloids (+) -stellettamide A and (-) -stellettamide B. On the other hand, intramolecular N, 0-acetalization of the keto-hydroxy-amines led to the one-step construction of the azabicyclononanes, which was then converted to the morphans. The azabicyclononane was subjected to bridgehead C-C bond formation with organometallic reagents via “anti-Bredt iminium ion” generated by treatment of aluminum reagents as Lewis acids. The 1-alkyl- and 1-vinylazabicyclononanes thus obtained were converted to the azatricyclododecane which is the core ring system of the novel immunosupressant FR 901483. The azabicyclononane formed by the N, O-acetalization of the keto-hydroxyamines was also elaborated into the diazatricyclododecane core of marine alkaloids madangamines.