Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A global and local desymmetrization approach to the synthesis of steroidal alkaloids: stereocontrolled total synthesis of paspaline.

ABSTRACT: A stereocontrolled total synthesis of the indole diterpenoid natural product paspaline is described. Key steps include a highly diastereoselective enzymatic desymmetrization, substrate-directed epoxidation, Ireland-Claisen rearrangement, and diastereotopic group selective C-H acetoxylation to assemble the target with excellent stereofidelity. The route and results described herein outline complementary conceptual disconnections in the arena of steroid natural product synthesis.

SUBMITTER: Sharpe RJ

PROVIDER: S-EPMC4409926 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

A global and local desymmetrization approach to the synthesis of steroidal alkaloids: stereocontrolled total synthesis of paspaline.

Sharpe Robert J RJ Johnson Jeffrey S JS

Journal of the American Chemical Society 20150409 15

A stereocontrolled total synthesis of the indole diterpenoid natural product paspaline is described. Key steps include a highly diastereoselective enzymatic desymmetrization, substrate-directed epoxidation, Ireland-Claisen rearrangement, and diastereotopic group selective C-H acetoxylation to assemble the target with excellent stereofidelity. The route and results described herein outline complementary conceptual disconnections in the arena of steroid natural product synthesis. ...[more]

PMID: 25856767

Similar Datasets

Stereocontrolled enantioselective total synthesis of the [2+2] quadrigemine alkaloids.

Project description:A unified strategy for enantioselective total synthesis of all stereoisomers of the 2+2 family of quadrigemine alkaloids is reported. In this approach, two enantioselective intramolecular Heck reactions are carried out at the same time on precursors fashioned in four steps from either meso- or (+)-chimonanthine to form the two critical quaternary carbons of the peripheral cyclotryptamine rings of these products. Useful levels of catalyst control are realized in either desymmetrizing a meso precursor or controlling diastereoselectivity in elaborating C2-symmetic intermediates. None of the synthetic quadrigemines are identical with alkaloids isolated previously and referred to as quadrigemines A and E. In addition, we report improvements in our previous total syntheses of (+)- or (-)-quadrigemine C that shortened the synthetic sequence to 10 steps and provided these products in 2.2% overall yield from tryptamine.

| S-EPMC4526107 | biostudies-literature

Stereocontrolled Total Synthesis of (-)-Stemaphylline.

Project description:Homologation of readily available ?-boryl pyrrolidines with metal carbenoids is especially challenging even when good leaving groups (Cl- ) are employed. By performing a solvent switch from Et2 O to CHCl3 , efficient 1,2-metalate rearrangement of the intermediate boronate occurs with both halide and ester leaving groups. The methodology was used in the total synthesis of the Stemona alkaloid (-)-stemaphylline in just 11 steps (longest linear sequence), with high stereocontrol (>20:1 d.r.) and 11?% overall yield. The synthesis also features a late-stage lithiation-borylation reaction with a tertiary amine containing carbenoid.

| S-EPMC5484348 | biostudies-literature

Bioinspired Diversification Approach Toward the Total Synthesis of Lycodine-Type Alkaloids.

Project description:Nitrogen heterocycles (azacycles) are common structural motifs in numerous pharmaceuticals, agrochemicals, and natural products. Many powerful methods have been developed and continue to be advanced for the selective installation and modification of nitrogen heterocycles through C-H functionalization and C-C cleavage approaches, revealing new strategies for the synthesis of targets containing these structural entities. Here, we report the first total syntheses of the lycodine-type Lycopodium alkaloids casuarinine H, lycoplatyrine B, lycoplatyrine A, and lycopladine F as well as the total synthesis of 8,15-dihydrohuperzine A through bioinspired late-stage diversification of a readily accessible common precursor, N-desmethyl-β-obscurine. Key steps in the syntheses include oxidative C-C bond cleavage of a piperidine ring in the core structure of the obscurine intermediate and site-selective C-H borylation of a pyridine nucleus to enable cross-coupling reactions.

| S-EPMC8017526 | biostudies-literature

Total synthesis of all (-)-Agelastatin alkaloids.

Project description:The pyrrole-imidazole family of marine alkaloids, derived from linear clathrodin-like precursors, constitutes a diverse array of structurally complex natural products. The bioactive agelastatins are members of this family that possess a tetracyclic molecular framework incorporating C4-C8 and C7-N12 bond connectivities. We provide a hypothesis for the formation of the unique agelastatin architecture that maximally exploits the intrinsic chemistry of plausible biosynthetic precursors. We report the concise enantioselective total syntheses of all known agelastatin alkaloids including the first total syntheses of agelastatins C, D, E, and F. Our gram-scale chemical synthesis of agelastatin A was inspired by our hypothesis for the biogenesis of the cyclopentane C-ring and required the development of new transformations including an imidazolone-forming annulation reaction and a carbohydroxylative trapping of imidazolones.

| S-EPMC3016719 | biostudies-literature

Total Synthesis of Dimeric HPI Alkaloids.

Project description:In this paper, we report a full account of the synthesis of dimeric hexahydropyrroloindole alkaloids and its analogues. The key feature of our new strategy is the novel catalytic copper (10 %) mediated intramolecular arylations of o-haloanilides followed by intermolecular oxidative dimerization of the resulting oxindoles in one pot. This sequential reaction leads to the key intermediates for the synthesis of (+)-chimonanthine, (+)-folicanthine, (-)-calycanthine and (-)-ditryptophenaline. In the presence of catalytic amount of cuprous iodide (10 %), an intramolecular arylation of o-haloanilides followed by an intermolecular oxidative dimerization of the resulting oxindoles leads to a common intermediate for the synthesis of (+)-chimonanthine, (+)-folicanthine and (-)-calycanthine. Based on this cascade sequence, we also developed a flexible strategy towards the asymmetric syntheses of dimeric HPI alkaloids (-)-ditryptophenaline and its analogues.

| S-EPMC4805652 | biostudies-literature

Total synthesis and cytotoxicity of Leucetta alkaloids.

Project description:The total synthesis of a number of representative natural products isolated from Leucetta and Clathrina sponges containing a polysubstituted 2-aminoimidazole are described. These syntheses take advantage of the site specific metallation reactions of 4,5-diiodoimidazoles resulting in the syntheses of three different classes of Leucetta derived natural products. The cytotoxicities of these natural products, along with several precursors in MCF7 cells were determined through an MTT growth assay. For comparative purposes a series of naphthimidazole-containing family members are included.

| S-EPMC5596918 | biostudies-literature

Enantioselective total synthesis of tricyclic myrmicarin alkaloids.

Project description:[reaction: see text] An enantioselective gram-scale synthesis of a key dihydroindolizine intermediate for the preparation of myrmicarin alkaloids is described. Key transformations in this convergent approach include a stereospecific palladium-catalyzed N-vinylation of a pyrrole with a vinyl triflate, a copper-catalyzed enantioselective conjugate reduction of a beta-pyrrolyl enoate, and a regioselective Friedel-Crafts reaction. The synthesis of optically active and isomerically pure samples of (4aR)-myrmicarins 215A, 215B, and 217 in addition to their respective C4a-epimers is presented.

| S-EPMC2992882 | biostudies-literature

Total synthesis and study of myrmicarin alkaloids.

Project description:The myrmicarins are a family of air- and temperature-sensitive alkaloids that possess unique structural features. Our concise enantioselective synthesis of the tricyclic myrmicarins enabled evaluation of a potentially biomimetic assembly of the complex members via direct dimerization of simpler structures. These studies revealed that myrmicarin 215B undergoes efficient and highly diastereoselective Brønsted acid-induced dimerization to generate a new heptacyclic structure, isomyrmicarin 430A. Mechanistic analysis demonstrated that heterodimerization between myrmicarin 215B and a conformationally restricted azafulvenium ion precursor afforded a functionalized isomyrmicarin 430A structure in a manner that was consistent with a highly efficient, non-concerted ionic process. Recent advancement in heterodimerization between tricyclic derivatives has enabled the preparation of strategically functionalized hexacyclic structures. The design and synthesis of structurally versatile dimeric compounds has greatly facilitated manipulation of these structures en route to more complex myrmicarin derivatives.

| S-EPMC2987668 | biostudies-literature

Total Synthesis of Novel Skeleton Flavan-Alkaloids.

Project description:The first total synthesis of novel skeleton natural compounds kinkeloids A and B, a group of newly discovered flavan alkaloids isolated from the African plant Combretum micranthum, are described in this study. The key and final step are achieved by Mannich reaction, through which the piperidine moiety couples to the flavan moiety. The identities of synthesized kinkeloids were further confirmed through a comparison with the ones in the plant leaves extract using LC/MS.

| S-EPMC7582810 | biostudies-literature

Studies for the synthesis of xenicane diterpenes. A stereocontrolled total synthesis of 4-hydroxydictyolactone.

Project description:The stereocontrolled total synthesis of 4-hydroxydictyolactone (4), a member of the xenicane diterpene family of natural products, is described. These studies feature the development of the B-alkyl Suzuki cross-coupling reaction for direct access to (E)-cyclononenes from acyclic precursors. The Ireland-Claisen rearrangement is effectively utilized to establish the backbone asymmetry of the contiguous C(2), C(3), C(10) stereotriad of 4. The synthesis strategy has devised an intramolecular Nozaki-Hiyama reductive allylation of a formate ester for the stereoselective formation of five-membered lactols 22. In addition, an internally directed S(E)' propargylation using allenylmagnesium bromide is described to establish the stereochemistry of the C(4) alcohol in 27, and the terminal alkyne is subsequently functionalized via a regioselective syn-silylstannylation to yield 30. Finally, the stereocontrolled phenylselenylation of the ester enolate derived from 43 leads to the desired syn-oxidative elimination to yield the natural product 4.

| S-EPMC2785454 | 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