Abstract
Evaluation of an hypothesis regarding the biomimetic synthesis of manzamine alkaloids from the stepwise condensation of malonate, aldehydes and primary amine derivatives is presented. The first part of this study was concentrated on the Knoevenagel reaction, with various aldehydes, of glutaconaldehydes 7 and their ester analogues 17 and 23, in order to prepare stable derivatives of dienes 8. This reaction, previously reported to work only with salicylaldehyde and glutaconic esters, appeared to be difficult to control in the case of the glutaconaldehyde derivative 7a, but was successful when starting from esters 17 and 23. This result allowed the preparation of new dienes 21, 22a−c, and 25. The second part of this paper reports preliminary results concerning the reactivity of diene 21 towards primary amines and aldehyde equivalents. Dienals such as 21 were found to react with primary amines to afford 1,2‐dihydropyridines such as 26 or 27. Diene 21 was also shown to give diastereoisomeric cycloadducts 30 or 32 with enamines or oxazolidine derivatives. The cycloadducts 30 were finally shown to react with n‐butylamine in acidic medium to give rearranged cyclopentenes 36 and 37. Although the synthesis of derivatives such as 9 or 10, corresponding to the AB ring system of manzamine A, by this approach have yet to be successful, the reported results reveal some new aspects of this multicomponent chemistry, some features of which are related to polyketide‐type condensations. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)