Tryptamine condensation with unsaturated

The first total synthesis of D/E-trans annellated yohimbines, e.g., ( )-yohim-bine (74) and ( )-pseudoyohimbine (88), was published in preliminary form by van Tamelen and co-workers (218) in 1958, while full details (219) appeared only in 1969. Key building block 393, prepared from butadiene and p-quinone, was condensed with tryptamine, yielding unsaturated amide 394, which was subsequently transformed to dialdehyde derivative 396. Cyclization of the latter resulted in pseudoyohimbane 397. Final substitution of ring E was achieved via pyrolysis, oxidation, and esterification steps. As a result of the reaction sequence, ( )-pseudoyohimbine was obtained, from which ( )-yohimbine could be prepared via C-3 epimerization. 

The direct condensation of unsaturated oxazolones with tryptamine in hydrochloric acid is an important and interesting case that deserves special attention. The reaction occurs via in situ hydrolysis of the oxazolone to a keto acid followed by a Pictet-Spengler-like reaction with tryptamine. This protocol affords a tetrahydro-p-carboline wherein the oxazolone is the synthetic equivalent of an arylacetalde-hyde. The reaction has been extended to substituted tryptamines 500 thus, allowing access to 1,3,4-trisubstituted tetrahydro-p-carbolines 501 as shown in Scheme 7.159. Some of these compounds have shown promising central nervous system activity. 

Szdntay s later synthesis (343) of 3-oxovincadifformine consisted essentially of an independent synthesis (Scheme 75) of Kuehne s tetracyclic aminoester 562a, which on debenzylation cyclized to 3-oxovincadifformine (97). The double bond was then introduced at the 14,15-position via the thiolactam, in a procedure reminiscent of that adopted by Magnus in his synthesis of 3-oxotabersonine (107). Desulfurization of the intermediate unsaturated thiolactam 586 gave yet another synthesis of tabersonine, whereas oxidative removal of the si r atom gave 3-oxotabersonine (107). Alternatively, condensation of the starting tryptamine derivative 587 with... 

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