Biomimetic Syntheses of (+/-)-Crambines A, B, C1, and C2. Revision of the Structures of Crambines B and C1

Article abstract of DOI:10.1021/jo00067a014

Crambines A (7) (eight steps, 22percent), B (45d) (eight steps, 19 percent), C1 (9d) (seven steps, 21 percent), and C2 (9a) (seven steps, 27percent) have been synthesized expediently and stereospecifically by a biomimetic route from methyl acetoacetate.Aminodihydropyrimidines 39 and 40 are formed efficiently from enone ester 36 by a two-step procedure involving addition of O-methylisourea to give methoxydihydropyrimidine 37 followed by displacement of the methoxy group of 37 with ammonia.Hydrogenolysis of 40a and 40d afford crambines C2 and C1, respectively.Mesylation of the alcohol of 39a or 40a followed by Et3N-catalyzed cyclization and hydrogenolysis affords crambine A (7).Aminal formation from 39d or 40d in CHCl3 followed by hydrogenolysis proceeds stereospecifically to provide crambine B (45d).The structure of crambine B has been revised to the stereochemistry shown in 45 and both crambines B and C1 have a seven rather than five-carbon guanidino alkyl chain.