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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: In the root extract of the curry leaf plant Murraya koenigii (Rutaceae), murrastifoline-F (3) was found to exist as a 56:44 mixture in favor of the M-enantiomer, by LC-CD coupling.
Abstract: The first total synthesis of the Murraya alkaloid murrastifoline-F (3), an unsymmetric, N,C-bonded heterobiarylic biscarbazole, is described. Starting from the likewise naturally occurring-but here synthetically prepared-"monomer" murrayafoline-A (6), lead tetraacetate-mediated oxidative non-phenolic biaryl coupling gives 3 as the main regioisomer. The existence of this natural product as a pair of stable atropo-enantiomers was demonstrated analytically through LC-CD investigations. Preparatively, the racemate resolution succeeded by O-demethylation, derivatization with Mosher's reagent, and chromatographic separation of the resulting diastereomers. The absolute configurations of the atropisomers were assigned by CD spectroscopy in combination with quantum chemical CD calculations at the stage of the alkaloid 3 and by ROESY experiments of the diastereomeric Mosher derivatives. In the root extract of the curry leaf plant Murraya koenigii (Rutaceae), murrastifoline-F (3) was found to exist as a 56:44 mixture in favor of the M-enantiomer, by LC-CD coupling.

171 citations

Journal ArticleDOI
18 Sep 2014-Nature
TL;DR: A facile multicomponent catalytic process that begins with a chemoselective, site-selective and diastereoselectively copper–boron addition to a monosubstituted allene and the resulting boron-substituting organocopper intermediates then participate in a similarly selective allylic substitution.
Abstract: Efficient catalytic reactions that can generate C–C bonds enantioselectively, and ones that can produce trisubstituted alkenes diastereoselectively, are central to research in organic chemistry. Transformations that accomplish these two tasks simultaneously are in high demand, particularly if the catalysts, substrates and reagents are inexpensive and if the reaction conditions are mild. Here we report a facile multicomponent catalytic process that begins with a chemoselective, site-selective and diastereoselective copper–boron addition to a monosubstituted allene; the resulting boron-substituted organocopper intermediates then participate in a similarly selective allylic substitution. The products, which contain a stereogenic carbon centre, a monosubstituted alkene and an easily functionalizable Z-trisubstituted alkenylboron group, are obtained in up to 89 per cent yield, with more than 98 per cent branch-selectivity and stereoselectivity and an enantiomeric ratio greater than 99:1. The copper-based catalyst is derived from a robust heterocyclic salt that can be prepared in multigram quantities from inexpensive starting materials and without costly purification procedures. The utility of the approach is demonstrated through enantioselective synthesis of gram quantities of two natural products, namely rottnestol and herboxidiene (also known as GEX1A). A catalytic process is reported that begins with a highly selective copper–boron addition to a monosubstituted allene, and in which the resulting boron-substituted organocopper intermediate then participates in a chemoselective, site-selective and enantioselective allylic substitution; this approach is used in the enantioselective synthesis of gram quantities of two natural products. This paper reports a catalytic process that combines two simple unsaturated organic molecules — a highly selective copper–diboron reagent and a monosubstituted allene — to produce a boron-substituted organocopper intermediate that then participates in a chemoselective, site-selective and enantioselective allylic substitution. The authors use this approach in the enantioselective synthesis of gram quantities of two natural products: the anti-tumour agent herboxidiene and stereoisomerically pure rottnestol, a hemiketal originally isolated from a marine sponge. Further development of this procedure should lead to economical protocols for the synthesis of other difficult-to-access alkenylboron-containing organocopper compounds.

171 citations

Journal ArticleDOI
TL;DR: An enantioselective total synthesis of (-)-rhazinilam highlights the potential utility of this reaction technology in target-oriented synthesis.
Abstract: Highly stereoselective Au(I)-catalyzed pyrrole additions to enantioenriched allenes afford a unique entry to optically active heterocycles. Asymmetric quaternary carbons can be installed with concurrent heterocycle annulation utilizing this methodology. The enantioenriched allenes are conveniently obtained by catalytic asymmetric acyl halide−aldehyde cyclocondensations and SN2‘ ring opening of the resulting enantioenriched β-lactones. An enantioselective total synthesis of (−)-rhazinilam highlights the potential utility of this reaction technology in target-oriented synthesis.

168 citations

Journal ArticleDOI
TL;DR: The first synthesis of the more complex, endoperoxide-containing members of this family of bioactive alkaloids, verruculogen and fumitremorgin A, is reported, proving to be a general way to functionalize the C6 position of an N,C3-disubstituted indole for the synthesis of indole-containing natural products and pharmaceuticals.
Abstract: Verruculogen and fumitremorgin A are bioactive alkaloids that contain a unique eight-membered endoperoxide. Although related natural products such as fumitremorgins B and C have been previously synthesized, we report the first synthesis of the more complex, endoperoxide-containing members of this family. A concise route to verruculogen and fumitremorgin A relied not only on a hydroperoxide/indole hemiaminal cyclization, but also on the ability to access the seemingly simple starting material, 6-methoxytryptophan. An iridium-catalyzed C–H borylation/Chan–Lam procedure guided by an N-TIPS group enabled the conversion of a tryptophan derivative into a 6-methoxytryptophan derivative, proving to be a general way to functionalize the C6 position of an N,C3-disubstituted indole for the synthesis of indole-containing natural products and pharmaceuticals.

168 citations


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