Abstract
Crambines A (7) (eight steps, 22%), B (45d) (eight steps, 19%), Cl (9d) (seven steps, 21%), and C2 (9a) (seven steps, 27%) 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 methoxydi- hydropyrimidine 37 followed by displacement of the methoxy group of 37 with ammonia. Hydrogenolysis of 40a and 40d afford crambines C2 and Cl, respectively. Mesylation of the alcohol of 39a or 40a followed by EtgN-catalyzed cyclization and hydrogenolysis affords crambine A (7). Aminal formation from 39d or 40d in CHCls 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 Cl have a seven rather than five-carbon guanidino alkyl chain.