Indoloquinolizidine ester

The structures of ebumaminol (155) and larutensine (154) have been confirmed by a synthesis reported by Lounasmaa from the previously available indoloquinolizidine ester 154 (Scheme 8). Successive reduction, acetylation and Fuji oxidation of 156 yielded the enamine 157 which was alkylated with iodoacetic ester followed by NaBH4 reduction to give a mixture of four products. Treatment of two of these, the epimeric esters 158, with ethanolic sodium ethoxide resulted in cyclization to 18-hydroxyebumamonine (159) accompanied by its C(20) epimer. Reduction of 18-hydroxyebumamonine furnished ( )-ebumaminol and 16-epiebumami-nol (160) which on overnight treatment with acid gave ( )-larutensine [114]. 

Two routes to (124) were developed, the shorter of which simply involved the reduction of the pyridinium salt (125) by means of sodium borohydride, followed by reduction of the tetrahydropyridine derivative (126) so obtained. The C n.m.r. spectra of a number of indoloquinolizidine esters prepared earlier in this programme of research have been determined, and complete assignments made. "... 

The naturally occurring indoloquinolizidine 499 was prepared by the reduction of the nicotinic ester salt 497 followed by cyclization, hydrolysis, and decarboxylation of the enaminone 498 (65JA5461). A number of quino-lizidines, including yohimboid, ajmalicinoid, and corynantheioid alkaloids. 

Lounasmaa et al. ° have continued their investigations into the synthesis of indoloquinolizidine derivatives, with particular reference to vallesiachotamine models. The most advanced work in this area to date involves synthesis (Scheme 9) of the closely related vallesiachotamine derivative (75). The critical stage in this synthesis was the reduction of the pyridinium salt (76) by means of sodium dithionite, which, in buffered (NaHC03) solution, allowed the isolation of the dihydropyridine derivative (77). Cyclization of (77) in the presence of acid gave, preferentially, the desired 3H,15H-trans-isomer (75), as had previously been established " in model systems. Alternatively, alkylation of the unsaturated ester (78) with tryptophyl bromide gave the pyridinium salt (79), which, on reduction with sodium dithionite in aqueous methanol, gave a mixture of (75) and the uncyclized tetrahydropyridine derivative (80). >yhen the sodium dithionite reduction medium was buffered (with NaHCOa), and the dihydropyridines so obtained were cyclized in acid, the products were the tetracyclic geometrical isomers of structure (81) (Scheme 9). 

Lounasmaa prepared various isomers in indoloquinolizidine series of alkaloids with orthoester rearrangement [88], Isositsirikine 371 derivatives were synthesized by the same group and NMR methods were applied to determine the configuration at C-16[89] (Scheme 6.62). Similarly, Lounasmaa extended these rearrangements to other functionalized orthoesters [90]. For instance, indoUc ketene acetal 374 afforded after rearrangement a mixture of diastereoisomeric esters 376 and... 

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