Enantioselective Total Syntheses of (+)-Arborescidine A, (−)-Arborescidine B, and (−)-Arborescidine C

Abstract

Described are the first enantioselective total syntheses of (+)-arborescidine A ((+)-1), (-)-arborescidine B ((-)-2), and (-)-arborescidine C ((-)-3), via routes that proceeded in five steps and 50% overall yield, eight steps and 61% overall yield, and nine steps and 51% overall yield, respectively, from 6-bromotryptamine (7). The syntheses feature the use of the Noyori catalytic asymmetric hydrogen-transfer reaction to introduce chirality in dihydro-beta-carbolines 6 and 8. On the basis of an ample precedent from Noyori's work, the reduction produces dihydro-beta-carbolines, and ultimately the natural products, possessing the R absolute configuration. The synthetic arborescidines displayed optical rotations that were opposite in sign those of the natural products, thereby supporting the S configuration for natural arborescidines A (1) and B (2) and the (3S,17S) configuration for natural arborescidine C (3). Our results are in agreement with the initial stereochemical assignment by Païs and co-workers, and are counter to their recently revised assignment.

The asymmetric total synthesis of (+)- and (-)-trypargine via Noyori asymmetric transfer hydrogenation

“…18 The reaction is catalyzed by chiral N-sulfonated diamine-Ru(II)-h 6 arene complexes and has become the method of choice for the enantioselective reduction of cyclic imines due to the high yield and enantiomeric excess usually attained and the simplicity of the experimental protocol. 19,20 Despite the advantages of this methodology, relatively few examples of asymmetric synthesis of natural products containing the tetrahydro-b-carboline core have appeared since our first disclosure of the application of Noyori asymmetric transfer hydrogenation in the total synthesis of arborescidines A, B and C. 8,9,[21][22][23] The 16 electron catalytic active species II was generated upon treatment of pre-catalyst RuCl(S,S)-H 2 NCHPhCHPhNTs)(h-p-cymene) (I) in DMF at 80 o C in the presence of Et 3 N. 24,25 Then, a solution of prochiral imine 9 in DMF was added, followed by a 5:2 formic acid-triethylamine azeotropic mixture and the reaction mixture was kept at room temperature for 8 h. Under these conditions tetrahydro-b-carboline 10 was isolated in 75% overall yield from allyl carbamate 4. However, when longer reaction time was employed the hydrogenation of the allyloxy group present in 10 was also observed.…”

“…8, 2009 imine. 8 Recently, Drabowicz and co-workers 9 disclosed the total synthesis of (+)-trypargine (1) via the latter approach which prompted us to disclose our results in this topic. …”

Pharmacokinetics and Metabolism of Streptochlorin and Its Synthetic Derivative, 5-Hydroxy-2′-isobutyl Streptochlorin, in Mice

“…M4 itself was found in several marine sources, such as marine sponges Rhopaloeides odorabile and Hyritios sp., 43) marine sponge Spongosorites sp., 44) and marine bryozoan Cryptpsula pallasiana sp. 45) It is also known to be an intermediate in the synthesis of marine natural products, such as arborescidines, 46) and is an endogenous ligand for aryl hydrocarbon receptor for treatment of cancer or immune system diseases.…”

Indolo[2,3-a]quinolizidines and Derivatives: Bioactivity and Asymmetric Synthesis

“…The enantioselective formal synthesis of ()-deplancheine (90), in a 9-step sequence from glutamic acid in good overall yields and high enantiomeric purity, was recently reported by Argade (Scheme 13). [52] A carbodiimide-induced coupling reaction of Boc-protected tryptamine 124 with enantiomerically pure (S)-tetrahydro-5-oxo-2-furancarboxylic acid (125), prepared from (S)-glutamic acid furnished amidolactone 126 in 86% yield and 96% enantiomeric purity.…”