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Total synthesis

About: Total synthesis is a research topic. Over the lifetime, 25578 publications have been published within this topic receiving 489319 citations.


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Journal ArticleDOI
TL;DR: A convergent diastereo- and enantioselective total synthesis of anti-HIV agent chloropeptin I is reported, performed in the presence of four unprotected phenols, two of which reside on dichlorophenylglycines.
Abstract: A convergent diastereo- and enantioselective total synthesis of anti-HIV agent chloropeptin I is reported. Important features of the total synthesis include: (1) the use of Ti-catalyzed cyanide addition to imines to prepare a requisite amino acid moiety, (2) the discovery of the positive effect of MeOH in the Cu-mediated biaryl ether formation to afford one of the two macrocyclic peptide moieties, and (3) the discovery of the positive influence of collidine in the diastereoselective Pd-mediated cross-coupling to result in efficient formation of another macrocycle within this medicinally important molecule. This key step is performed in the presence of four unprotected phenols, two of which reside on dichlorophenylglycines.

150 citations

Journal ArticleDOI
TL;DR: An efficient stereoselective synthesis of the orally active NK(1) receptor antagonist Aprepitant is described, and the targeted clinical candidate was obtained in 55% overall yield over the longest linear sequence.
Abstract: An efficient stereoselective synthesis of the orally active NK1 receptor antagonist Aprepitant is described. A direct condensation of N-benzyl ethanolamine with glyoxylic acid yielded a 2-hydroxy-1,4-oxazin-3-one which was activated as the corresponding trifluoroacetate. A Lewis acid mediated coupling with enantiopure (R)-1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-ol afforded a 1:1 mixture of acetal diastereomers which was converted into a single isomer via a novel crystallization-induced asymmetric transformation. The resulting 1,4-oxazin-3-one was converted via a unique and highly stereoselective one-pot process to the desired α-(fluorophenyl)morpholine derivative. Interesting and unexpected [1,2]-Wittig and [1,3]-sigmatropic rearrangements were identified during the optimization of these key steps. In the final step, a triazolinone side chain was appended to the morpholine core. The targeted clinical candidate was thus obtained in 55% overall yield over the longest linear sequence.

150 citations

Journal ArticleDOI
TL;DR: A concise and efficient total synthesis of the acyl-CoA:cholesterol acyltransferase inhibitor gypsetin is described and the reaction of nucleophiles with in situ-generated 3-chloroindolenines provides a route to 2,3-disubstituted indoles from 3-substituting precursors.
Abstract: A concise and efficient total synthesis of the acyl-CoA:cholesterol acyltransferase inhibitor gypsetin (1) is described. The route features a straightforward method for the introduction of a reverse prenyl group into the C2-position of an N-phthaloyl-protected tryptophan (11). The total synthesis of gypsetin was completed by the dimethyldioxirane-promoted double-oxidative cyclization of a prefashioned diketopiperazine (19). Total syntheses of deoxybrevianamide E (24) and brevianamide E (25) following similar procedures are also described. The reaction of nucleophiles with in situ-generated 3-chloroindolenines provides a route to 2,3-disubstituted indoles from 3-substituted precursors. Indications of the scope and limitations of such reactions are provided. A total synthesis of tryprostatin B (41), a diketopiperazine derived from an l-tryptophan derivative (bearing a prenyl group at the α position of the indole) and l-proline, was accomplished. The key step involved the introduction of the prenyl function ...

150 citations

Journal ArticleDOI
TL;DR: In this article, a highly stereoselective and systematic strategy for the introduction of polysulfides in the synthesis of epipolythiodiketopiperazines is described.
Abstract: A highly stereoselective and systematic strategy for the introduction of polysulfides in the synthesis of epipolythiodiketopiperazines is described. We report the first total synthesis of dimeric epitri- and epitetrathiodiketopiperazines.

150 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
2023245
2022592
2021479
2020451
2019497
2018551