Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Total syntheses of arylindolizidine alkaloids (+)-ipalbidine and (+)-antofine.

ABSTRACT: This paper presents the first application of two recently developed reactions to natural product synthesis. The first method involves a 6-endo-trig cyclization to prepare a versatile chiral enaminone building block. The second is a direct C-H arylation reaction. As a showcase for the utility of these methods, (+)-antofine and (+)-ipalbidine were synthesized in only 8 steps and 24-26% overall yields.

SUBMITTER: Niphakis MJ

PROVIDER: S-EPMC2948484 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Total syntheses of arylindolizidine alkaloids (+)-ipalbidine and (+)-antofine.

Niphakis Micah J MJ Georg Gunda I GI

The Journal of organic chemistry 20100901 17

This paper presents the first application of two recently developed reactions to natural product synthesis. The first method involves a 6-endo-trig cyclization to prepare a versatile chiral enaminone building block. The second is a direct C-H arylation reaction. As a showcase for the utility of these methods, (+)-antofine and (+)-ipalbidine were synthesized in only 8 steps and 24-26% overall yields. ...[more]

PMID: 20704319

Similar Datasets

Total synthesis of (+)-antofine and (-)-cryptopleurine.

Project description:The tylophorine alkaloid anticancer compounds antofine and cryptopleurine have been synthesized in optically active form. Both syntheses employ optically pure α-amino acids as the starting materials, require only seven steps from known 2-ethynylpyrrolidine or 2-ethynylpiperidine derivatives, and are free of protecting groups. Key steps include an alkyne hydration and a chromium carbene complex based net [5+5]-cycloaddition step. Alkyne hydration was accompanied by racemization of the resulting β-aminoketone under most of the conditions examined, and successful minimization of this side reaction was achieved through careful pH control and choice of metal additive. Final ring closure involves a Bischler-Napieralski reaction using a carbamate (antofine) or urea (cryptopleurine) precursor.

| S-EPMC3864684 | biostudies-literature

Enantioselective Total Syntheses of Methanoquinolizidine-Containing Akuammiline Alkaloids and Related Studies.

Project description:The akuammiline alkaloids are a structurally diverse class of bioactive natural products isolated from plants found in various parts of the world. A particularly challenging subset of akuammiline alkaloids are those that contain a methanoquinolizidine core. We describe a synthetic approach to these compounds that has enabled the first total syntheses of (+)-strictamine, (-)-2( S)-cathafoline, (+)-akuammiline, and (-)-?-akuammigine. Our strategy relies on the development of the reductive interrupted Fischer indolization reaction to construct a common pentacyclic intermediate bearing five contiguous stereocenters, in addition to late-stage formation of the methanoquinolizidine framework using a deprotection-cyclization cascade. The total syntheses of (-)-?-akuammigine and (+)-akuammiline mark the first preparations of akuammiline alkaloids containing both a methanoquinolizidine core and vicinal quaternary centers. Lastly, we describe the bioinspired reductive rearrangements of (+)-strictamine and (+)-akuammiline to ultimately provide (-)-10-demethoxyvincorine and a new analogue thereof.

| S-EPMC6085837 | biostudies-literature

Calyciphylline B-Type Alkaloids: Total Syntheses of (-)-Daphlongamine H and (-)-Isodaphlongamine H.

Project description:The first total synthesis of the complex hexacylic Daphniphyllum alkaloid (-)-daphlongamine H has been accomplished. Key to the success of the strategy are a complexity-building Mannich reaction, efficient cyclizations, and a highly diastereoselective hydrogenation to assemble multigram quantities of the tricyclic core bearing four contiguous stereocenters. Following construction of the hydro-indene substructure by means of a Pauson-Khand reaction, endgame redox manipulations delivered the natural product. Importantly, the synthetic studies have also given access to (-)-isodaphlongamine H and led to a revision of the reported structure of deoxyisocalyciphylline B.

| S-EPMC6750003 | biostudies-literature

Concise total syntheses of the Lycopodium alkaloids (+/-)-nankakurines A and B via luciduline.

Project description:Total syntheses of the Lycopodium alkaloids nankakurines A and B have been accomplished in 6 and 7 steps, respectively, via a sequence that passes through a third Lycopodium alkaloid, luciduline, and forgoes the use of protecting groups on nitrogen. Key features include a short preparation of luciduline followed by a concise and stereoselective aminoallylation/ring-closing metathesis protocol to fashion the spiropiperidine ring common to nankakurines A and B.

| S-EPMC2804776 | biostudies-literature

Unified total syntheses of fawcettimine class alkaloids: fawcettimine, fawcettidine, lycoflexine, and lycoposerramine B.

Project description:The total syntheses of the lycopodium alkaloids fawcettimine, fawcettidine, lycoflexine, and lycoposerramine B have been accomplished through an efficient, unified, and stereocontrolled strategy that relies on a Diels-Alder reaction to construct the cis-fused 6,5-carbocycles with one all-carbon quaternary center. Access to the enantioselective syntheses of both antipodes of those alkaloids can be achieved by kinetic resolution of the earliest intermediate via a Sharpless asymmetric dihydroxylation (Sharpless AD). Compared to existing approaches to these alkaloids, our synthetic route possesses superior stereocontrol over the C-4 and C-15 stereogenic centers as well as allowing for more functional variation on the 6-membered ring.

| S-EPMC3448369 | biostudies-literature

Enantioselective Total Syntheses of Akuammiline Alkaloids (+)-Strictamine, (-)-2(S)-Cathafoline, and (-)-Aspidophylline A.

Project description:The akuammiline alkaloids are a family of natural products that have been widely studied for decades. Although notable synthetic achievements have been made recently, akuammilines that possess a methanoquinolizidine core have evaded synthetic efforts. We report an asymmetric approach to these alkaloids, which has culminated in the first total syntheses of (-)-2(S)-cathafoline and the long-standing target (+)-strictamine. Moreover, the first enantioselective total synthesis of aspidophylline A is described.

| S-EPMC5154302 | biostudies-literature

Total syntheses of the monoterpene indole alkaloids (±)-alstilobanine A and E and (±)-angustilodine.

Project description:A synthetic strategy has been developed culminating in stereoselective total syntheses of the small class of unusual monoterpenoid indole alkaloids exemplified by alstilobanines A (3) and E (2) and angustilodine (1). A pivotal step includes a novel intermolecular Michael-type addition of an indole ester dianion to a piperidine-derived nitrosoalkene to form the C15, C16 bond of the alkaloids. In addition, an application of the Romo protocol for effecting a stereoselective intramolecular nucleophile-assisted aldol-lactonization was employed, leading to a β-lactone incorporating the requisite cis-fused 2-azadecalin moiety and also setting the C15, C19, C20 relative stereochemistry of the metabolites. It was then possible to stereoselectively effect an aldolization of a dianion derived from this indole ester β-lactone intermediate with formaldehyde to introduce the requisite C16 hydroxymethyl group. Further manipulations of the system ultimately led to the three alkaloids in racemic form.

| S-EPMC3913098 | biostudies-literature

Total syntheses of indolactam alkaloids (-)-indolactam V, (-)-pendolmycin, (-)-lyngbyatoxin A, and (-)-teleocidin A-2.

Project description:We report the total syntheses of (-)-indolactam V and the C7-substituted indolactam alkaloids (-)-pendolmycin, (-)-lyngbyatoxin A, and (-)-teleocidin A-2. The strategy for preparing indolactam V relies on a distortion-controlled indolyne functionalization reaction to establish the C4-N linkage, in addition to an intramolecular conjugate addition to build the conformationally-flexible nine-membered ring. The total synthesis of indolactam V then sets the stage for the divergent synthesis of the other targeted alkaloids. Specifically, late-stage sp2-sp3 cross-couplings on an indolactam V derivative are used to introduce the key C7 substituents and the necessary quaternary carbons. These challenging couplings, in addition to other delicate manipulations, all proceed in the presence of a basic tertiary amine, an unprotected secondary amide, and an unprotected indole. Thus, our approach not only enables the enantiospecific total syntheses of four indolactam alkaloids, but also serves as a platform for probing complexity-generating and chemoselective transformations in the context of alkaloid total synthesis.

| S-EPMC4019407 | biostudies-literature

Total Syntheses and Biological Evaluation of Both Enantiomers of Several Hydroxylated Dimeric Nuphar Alkaloids.

Project description:Herein, we describe the first total syntheses of five members of the dimeric nuphar alkaloids: (+)-6,6'-dihydroxythiobinupharidine (+)-1?a, (+)-6-hydroxythiobinupharidine (+)-1?b, (-)-6,6'-dihydroxythionuphlutine (-)-2?a, (-)-6,6'-dihydroxyneothiobinupharidine (-)-3?a, and (+)-6,6'-dihydroxyneothionuphlutine (+)-4?a. The latter two have not been found in nature. We have also made each of their enantiomers (-)-1?a-b, (+)-2?a, (+)-3?a, and (-)-4?a. The key step in these syntheses was the dimerization of an ?-aminonitrile (a hydrolytically stable surrogate for its corresponding hemiaminal) with chiral Lewis acid complexes. We have also reassigned the literature structures of (+)-1?a-1?b—for those instances in which the NMR spectra were obtained in CD3OD—to their corresponding CD3O-adducts. Our efforts provide for the first time apoptosis data for (-)-3?a, (+)-4?a, and all five non-natural enantiomers prepared. The data indicate high apoptotic activity regardless of the enantiomer or relative stereochemical configuration at C7 and C7'.

| S-EPMC4691328 | biostudies-literature

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

Project description: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.

| S-EPMC7467818 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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