An enantioselective total synthesis of (+)-geissoschizine

[formula: see text] A concise asymmetric synthesis of the indole alkaloid (+)-geissoschizine (1) has been completed. The synthesis features the highly diastereoselective vinylogous Mannich reaction of 3 with 4 to give 5, which is elaborated into the key tetracyclic intermediate 7 in two steps. Following the stereoselective introduction of the ethylidene moiety to give 9, reduction of the lactam and radical decarboxylation via an acyl selenide gave 12, which was converted into (+)-geissoschizine by formylation. The synthesis requires only 11 chemical operations and proceeds in an overall yield of 17%.     

A new entry to Amaryllidaceae alkaloids from carbohydrates: total synthesis of (+)-vittatine

The stereoselective and chiral synthesis of the Amaryllidaceae alkaloid, (+)-vittatine 1, is described; the quaternary carbon in 1 was generated by Claisen rearrangement of a cyclohexenol derived from D-glucose by way of a Ferrier's carbocyclisation reaction and a hexahydroindole skeleton was effectively constructed by intramolecular aminomercuration-demercuration, followed by Chugaev reaction.     

Biomimetic synthesis of the antimalarial flindersial alkaloids

A biomimetic strategy for the synthesis of the antimalarial flindersial alkaloids is described. Flinderoles A, B, and C, desmethylflinderole C, isoborreverine, and dimethylisoborreverine were all synthesized in three steps from tryptamine. The key step is an acid-promoted dimerization of the natural product borrerine. This approach is thought to mirror the biosynthesis of these compounds.     

An asymmetric synthesis of indole alkaloids

Chiral formamidines derived from β-carbolines are metallated and alkylated stereoselectively opening a route to indole alkaloids and analogous compounds.     

A new synthetic entry to pentacyclic Strychnos indole alkaloids

Cyclization of the thionium ion generated by DMTSF treatment of dithioacetal 15 constitutes a new synthetic entry to the pentacyclic ring system of Strychnos indole alkaloids.     

Palladium-mediated domino oxidative amination of cyclohexadienes as an entry to indole alkaloids

A palladium-mediated double oxidative amination reaction on cyclohexa-2,5-dienes has been developed, leading to the tetracyclic indoline skeleton of aspidosperma and strychnos alkaloids. The allyl-palladium intermediate, generated after the double oxidative amination, could be trapped by an internal nucleophile to allow the construction of 3 rings in a single step. Approaches to the synthesis of strychnine and mossambine is finally reported.     

Tremorgenic indole alkaloids. The total synthesis of (-)-penitrem D

A convergent, stereocontrolled total synthesis of the architecturally complex tremorgenic indole alkaloid (-)-penitrem D (4) has been achieved. Highlights of the synthesis include an efficient, asymmetric synthesis of the western hemisphere; the stereocontrolled assembly of the I-ring; discovery of a novel autoxidation to introduce the C(22) tertiary hydroxyl group, required for tremorgenic activity; union of fully elaborated eastern and western hemispheres, exploiting an indole synthetic protocol developed expressly for this purpose; and a late-stage, stereoselective construction of the A and F rings exploiting a Sc(OTf)(3-)promoted reaction cascade. The longest linear sequence leading to (-)-penitrem D (4) was 43 steps.     

Total synthesis of the indole alkaloids ngouniensine and epingouniensine

The first total synthesis of ngouniensine and epingouniensine, by cyclization of a suitable 1-(3-indolylethyl)piperidine-2-carboxylic acid followed by the elaboration of the exocyclic methylene group, is reported.     

Towards a total synthesis of the manadomanzamine alkaloids: the first asymmetric construction of the pentacyclic indole core

We report a highly diastereoselective approach for the synthesis of the pentacyclic indole core of the manadomanzamine alkaloid skeleton, with complete control over the relative and absolute stereochemistries at the three contiguous stereocentres at ring positions 1, 10, and 24, from a readily available chiral template.     

Fluorous and traceless synthesis of substituted indole alkaloids

The fluorous traceless synthesis of substituted indole alkaloids is carried out first by attaching the 3-(perfluorooctyl)propanol with Boc protected L-tryptophan. The reaction of perfluoroalkyl (Rfh)-tagged tryptophan esters with various aldehydes undergoes Pictet-Spengler reaction to give cis and trans stereoisomers of tetrahydro-beta-carbolines. The nucleophilic addition of the piperidine nitrogen across various isocyanates is followed by the cyclization of ureas and simultaneous rupture of the fluorous tag to afford the hydantoin ring fused tetrahydro-beta-carbolines. All the fluorous-tag compounds are purified by solid-phase extraction (SPE) through Fluoro Flash cartridges.     

Total synthesis of the indole alkaloids henrycinol A and B

The total synthesis of new indole alkaloids henrycinol A and B were accomplished starting from l-tryptophan methyl ester. The key step is a stereochemically flexible Pictet–Spengler reaction governed by the presence or absence of an N-allyl group in the tryptophan precursor. The natural products henrycinol A and B were synthesized in good overall yield in eight and nine steps, respectively.     

A new entry into the synthesis of the strychnos indole alkaloids containing 19,20-double bond via the thio-claiser rearrangement

A simple and selective route to the Strychnos framework containing 19,20-double bond has been developed employing the thio-Claisen rearrangement.     

Transformation of indole alkaloids—I : Conversion of oxindole alkaloids into indole alkaloids

Chemical conversion of some natural oxindoles (pteropodine, isopteropodine and isorhynchophylline) into the corresponding indole alkaloids has been made by way of a sequence of reactions which include formation of iminoethers of the natural oxindoles with Meerwein's reagent, reduction of the iminoethers to 2,3-seco-indoles and cyclization of 2,3-seco-indoles to the desired natural indole alkaloids. Sodium borohydride in acetic acid was found to be a specific reagent for the reduction of oxindole-iminoethers to 2,3-seco-indoles which were the key intermediates in these transformations. Yohimbine-oxindole iminoether was similarly converted to yohimbine and pseudoyohimbine. A number of by-products were obtained and their structures were elucidated.     

Biomimetic total synthesis of (+)-gelsemine

Challenging: (+)-gelsemine was synthesized from (R,R)-aziridine 1 in 25 steps with approximately 1 % overall yield. A multistep, one-pot enol-oxonium cyclization cascade was used to construct, simultaneously, the E ring, F ring, C3 stereocenter, and C7 quaternary stereocenter. This synthesis using the enol-oxonium cyclization reaction as a key step to make the cage structure has demonstrated the proposed biosynthetic pathway of the gelsemine family.     

Biomimetic total synthesis of (+)-himbacine

On treatment with trifluoroacetic acid butenolide 14 undergoes N-Boc deprotection and condensation followed by an iminium ion activated intramolecular Diels-Alder cycloaddition to give the (+)-himbacine precursor 11 on reductive work up. Compound 11 was converted into (+)-himbacine in four synthetic steps. [reaction: see text]     

A new approach to the synthesis of pentacyclic indole derivatives related to Aspidosperma alkaloids

N-Indolylethyl-2-pyridones bearing appropriate β-dicarbonyl substituents in the 3-position have been cyclised to pentacyclic indoles via spirocyclic indolenines by catalysis with trifluoroacetic anhydride.