Browse
Submit Data
Databases
API
Help

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Total Syntheses of Dihydroindole Aspidosperma Alkaloids: Reductive Interrupted Fischer Indolization Followed by Redox Diversification.

ABSTRACT: We report a novel reductive interrupted Fischer indolization process for the concise assembly of the 20-oxoaspidospermidine framework. This rapid complexity generating route paves the way toward various dihydroindole Aspidosperma alkaloids with different C-5 side chain redox patterns. The end-game redox modulations were accomplished by modified Wolff-Kishner reaction and photo-Wolff rearrangement, enabling the total synthesis of (-)-aspidospermidine, (-)-limaspermidine, and (+)-17-demethoxy-N-acetylcylindrocarine and the formal total synthesis of (-)-1-acetylaspidoalbidine.

SUBMITTER: Martin G

PROVIDER: S-EPMC7467818 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Total Syntheses of Dihydroindole <i>Aspidosperma</i> Alkaloids: Reductive Interrupted Fischer Indolization Followed by Redox Diversification.

Martin Gábor G Angyal Péter P Egyed Orsolya O Varga Szilárd S Soós Tibor T

Organic letters 20200604 12

We report a novel reductive interrupted Fischer indolization process for the concise assembly of the 20-oxoaspidospermidine framework. This rapid complexity generating route paves the way toward various dihydroindole <i>Aspidosperma</i> alkaloids with different C-5 side chain redox patterns. The end-game redox modulations were accomplished by modified Wolff-Kishner reaction and photo-Wolff rearrangement, enabling the total synthesis of (-)-aspidospermidine, (-)-limaspermidine, and (+)-17-demetho ...[more]

PMID: 32497431

Similar Datasets

Interrupted Fischer indolization approach toward the communesin alkaloids and perophoramidine.

Project description:A concise approach toward the total synthesis of the communesin alkaloids and perophoramidine is reported. The strategy relies on the use of the interrupted Fischer indolization to build the tetracyclic indoline core of the natural products. Studies to probe the scope and limitations of this plan are presented. Although the methodology does not tolerate a C8-allyl substituent en route to the challenging vicinal quaternary stereocenters, variation at C7 and on the C ring is permitted.

| S-EPMC3445034 | biostudies-literature

Exploration of the interrupted Fischer indolization reaction.

Project description:A convergent method to access the fused indoline ring system present in a multitude of bioactive molecules has been developed. The strategy involves the condensation of hydrazines with latent aldehydes to ultimately deliver indoline-containing products by way of an interrupted Fischer indolization sequence. The method is convergent, mild, operationally simple, broad in scope, and can be used to access enantioenriched products. In addition, our approach is amenable to the synthesis of furoindoline and pyrrolidinoindoline natural products as demonstrated by the concise formal total syntheses of physovenine and debromoflustramine B. The strategy will likely enable the synthesis of more complex targets such as the communesin alkaloids.

| S-EPMC2925302 | biostudies-literature

Synthesis of Fused Indolines by Interrupted Fischer Indolization in a Microfluidic Reactor.

Project description:This study describes our development of a microfluidic reaction scheme for the synthesis of fused indoline ring systems found in several bioactive compounds. We have utilized a continuous-flow microfluidic reactor for the reaction of hydrazines with latent aldehydes through the interrupted Fischer indolization reaction to form fused indoline and azaindoline products. We have identified optimal conditions and evaluated the scope of this microfluidic reaction using various hydrazine and latent aldehyde surrogates. This green chemistry approach can be of general utility to rapidly produce indoline scaffolds and intermediates in a continuous manner.

| S-EPMC6322698 | biostudies-literature

A FISCHER INDOLIZATION STRATEGY TOWARD THE TOTAL SYNTHESIS OF (-)-GONIOMITINE.

Project description:A Fischer indolization strategy toward the core of (-)-goniomitine is reported. Initial investigations into the Pd-catalyzed asymmetric allylic alkylation of dihydropyrido[1,2-a]indolone (DHPI) substrates are also discussed.

| S-EPMC5502790 | biostudies-literature

Homologation of the Fischer Indolization: A Quinoline Synthesis via Homo-Diaza-Cope Rearrangement.

Project description:We disclose a new Brønsted acid promoted quinoline synthesis, proceeding via homo-diaza-Cope rearrangement of N-aryl-N'-cyclopropyl hydrazines. Our strategy can be considered a homologation of Fischer's classical indole synthesis and delivers 6-membered N-heterocycles, including previously inaccessible pyridine derivatives. This approach can also be used as a pyridannulation methodology toward constructing polycyclic polyheteroaromatics. A computational analysis has been employed to probe plausible activation modes and to interrogate the role of the catalyst.

| S-EPMC7693176 | biostudies-literature

Structural basis of cycloaddition in biosynthesis of iboga and aspidosperma alkaloids.

Project description:Cycloaddition reactions generate chemical complexity in a single step. Here we report the crystal structures of three homologous plant-derived cyclases involved in the biosynthesis of iboga and aspidosperma alkaloids. These enzymes act on the same substrate, named angryline, to generate three distinct scaffolds. Mutational analysis reveals how these highly similar enzymes control regio- and stereo-selectivity.

| S-EPMC7104359 | biostudies-literature

Concise and enantioselective total synthesis of (-)-mehranine, (-)-methylenebismehranine, and related Aspidosperma alkaloids.

Project description:We report an efficient and highly stereoselective strategy for the synthesis of Aspidosperma alkaloids based on the transannular cyclization of a chiral lactam precursor. Three new stereocenters are formed in this key step with excellent diastereoselectivity due to the conformational bias of the cyclization precursor, leading to a versatile pentacyclic intermediate. A subsequent stereoselective epoxidation followed by a mild formamide reduction enabled the first total synthesis of the Aspidosperma alkaloids (-)-mehranine and (+)-(6S,7S)-dihydroxy-N-methylaspidospermidine. A late-stage dimerization of (-)-mehranine mediated by scandium trifluoromethanesulfonate completed the first total synthesis of (-)-methylenebismehranine.

| S-EPMC4240000 | biostudies-literature

Antiproliferative Aspidosperma-Type Monoterpenoid Indole Alkaloids from Bousigonia mekongensis Inhibit Tubulin Polymerization.

Project description:Monoterpenoid indole alkaloids are structurally diverse natural products found in plants of the family Apocynaceae. Among them, vincristine and its derivatives are well known for their anticancer activity. Bousigonia mekongensis, a species in this family, contains various monoterpenoid indole alkaloids. In the current study, fourteen known aspidosperma-type monoterpenoid indole alkaloids (1?14) were isolated and identified from a methanol extract of the twigs and leaves of B. mekongensis for the first time. Among them, compounds 3, 6, 9, and 13 exhibited similar antiproliferative activity spectra against A549, KB, and multidrug-resistant (MDR) KB subline KB-VIN cells with IC50 values ranging from 0.5?0.9 ?M. The above alkaloids efficiently induced cell cycle arrest at the G2/M phase by inhibiting tubulin polymerization as well as mitotic bipolar spindle formation. Computer modeling studies indicated that compound 7 likely forms a hydrogen bond (H-bond) with ?- or ?-tubulin at the colchicine site. Evaluation of the antiproliferative effects and SAR analysis suggested that a 14,15-double bond or 3?-acetonyl group is critical for enhanced antiproliferative activity. Mechanism of action studies demonstrated for the first time that compounds 3, 4, 6, 7, and 13 efficiently induce cell cycle arrest at G2/M by inhibiting tubulin polymerization by binding to the colchicine site.

| S-EPMC6480704 | biostudies-literature

A Route to the C,D,E Ring System of the Aspidosperma Alkaloids.

Project description:A short synthetic sequence leading to the formation of the C,D,E-ring subunit of the Aspidosperma alkaloids is reported. This route is based on a ring fragmentation/intramolecular azomethine ylide 1,3-dipolar cycloaddition reaction sequence that gives the desired tricyclic product as a single diastereomer. A ?-amino-?-hydroxy-?-diazo carbonyl compound is shown to fragment in the presence of a Lewis acid to give an iminium product that can be directly reduced to the corresponding amine.

| S-EPMC4994716 | biostudies-literature

Formal synthesis of aspidosperma alkaloids via the intramolecular [3 + 2] cycloaddition of 2-azapentdienyllithiums.

Project description:[reaction: see text] A formal synthesis of the Aspidosperma alkaloids aspidospermidine, aspidospermine, and quebrachamine is reported through an efficient preparation of Stork's penultimate intermediate. The key step of the sequence involved an intramolecular [3 + 2] cycloaddition of the 2-azapentadienyllithium 21 formed in situ from the corresponding imine 1, which after N-alkylation of the resulting cycloadduct provided 2 in excellent yield. The synthesis represents a new disconnection of the classical tricyclic ketone used for appendage of the requisite indole.

| S-EPMC2538914 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data