Stereospecificity in the Pictet-Spengler Reaction. Enantiospecific Synthesis of (6S,10S)-(-)-5-Methyl-9-oxo-12-benzyl-6,7,8,9,10,11-hexahydro-6,10-imino-5H-cyclooct[b]indole, a Template for Preparation of Macroline/Sarpagine Alkaloids

The synthesis [from D(+)-tryptophan] of the tetracyclic ketone [(-)-lb] was carried out in enantiospecific fashion (>98% ee) via the 1,341ansfer of chirality from Na-methyl, Nb-benzyl tryptophan methyl ester [(+)-I41 to the t m diastereomer [(-)4b] in the Pictet-Spengler reaction.Although the condensation of 14 with aldehyde (15) in refluxing benzene generated the tetrahydro Dcarbolines (4b/5b) in a kinetic ratio (72:28), epimerization (C-1) of the cir diastereomer [(+)-5b] into the tmm isomer [(-)4b] occurred stereospecifically under acidic conditions.Dieckmann cyclization of either the Na-methyl, Nbbenzylcir-(+)-5b or m-(-)-4b diastereomer provided the cir-bicyclo[3.3.1]azanonanesystem at approximately the same rate, although the D-keto esters were antipodal, in contrast to results reported in the Na-benzyl series by Magnus.Over fifty indole alkaloids isolated from Alstonia rnue~leriana,~ Alstonia rnacrophylla2 and other Alstonia species possess the basic tetracyclic skeleton (1) depicted in Scheme I.