An important side reaction in the first stage of the two-step alkaloid synthesis scheme, involving the addition of carbon nucleophiles to l-alkyl-3-acylpyridinium salts and acid-catalyzed cyclization of the resultant 1,4-dihydropyridines, is shown to be the formation of 1,6-dihydropyridines, followed by pyridine ring opening. The dimer (or oligomer), prepared by the reaction of base with the salt from the N-alkylation of methyl ß-{ßpyridyl)acrylate with tryptophyl bromide, produces a 6-(trichloromethyl)-1,6-dihydropyridine and a 4-(trichloromethyl)-!,4-dihydropyridine on reaction with chloroform. Heating converts the former product into the latter, which on acid treatment undergoes ring closure. The two-step alkaloid synthesis procedure is shown to work well with the use of the lithio salt of methylthioacetic esters acting as the initial carbon nucleophile.The two-step reaction sequence of the addition of carbon nucleophiles to l-alkyl-3-acylpyridinium salts or their equivalents and the acid-induced cyclization of the resultant 1,4-dihydropyridines has been the foundation stone of total syntheses of a variety of indole alkaloids (Scheme I, path A).1 Whereas despite the structural complexity of the natural bases their syntheses were composed of a few, high-yielding reactions, the yields of the early two-step sequence were always low. Since the nucleophile-pyridine interaction, in principle, could take place at «-or 7-carbon sites on the pyridine nucleus, it had been assumed that, to the extent a kinetic «-addition product had been an intermediate, its equilibration with the thermodynamic 7-addition product had been blocked (partly or fully) by a competitive, irreversible side reaction of an undesirable decomposition mode. Whereas thus the major, albeit unwanted, products of the two-reaction procedure never

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The cleavage of NH2-tyrosine dipeptides with C6H51(OAc)2-MeOH-KOH yields 4-(methoxymethyl)phenol.We report a specific cleavage reaction of NH2-terminal tyrosyl peptides as expressed in Scheme 1 and summarised in Table 1.

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Abstract A synthesis of vincamine (1) and eburnamo-nine (2) is reported which involves a new route to the key intermediate (8).