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Keywords = zinc carbenoids

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16 pages, 3066 KiB  
Article
Synthesis of Novel C/D Ring Modified Bile Acids
by Roselis A. Landaeta Aponte, Andreas Luxenburger, Scott A. Cameron, Alex Weymouth-Wilson, Richard H. Furneaux, Lawrence D. Harris and Benjamin J. Compton
Molecules 2022, 27(7), 2364; https://doi.org/10.3390/molecules27072364 - 6 Apr 2022
Cited by 3 | Viewed by 3224
Abstract
Bile acid receptors have been identified as important targets for the development of new therapeutics to treat various metabolic and inflammatory diseases. The synthesis of new bile acid analogues can help elucidate structure–activity relationships and define compounds that activate these receptors selectively. Towards [...] Read more.
Bile acid receptors have been identified as important targets for the development of new therapeutics to treat various metabolic and inflammatory diseases. The synthesis of new bile acid analogues can help elucidate structure–activity relationships and define compounds that activate these receptors selectively. Towards this, access to large quantities of a chenodeoxycholic acid derivative bearing a C-12 methyl and a C-13 to C-14 double bond provided an interesting scaffold to investigate the chemical manipulation of the C/D ring junction in bile acids. The reactivity of this alkene substrate with various zinc carbenoid species showed that those generated using the Furukawa methodology achieved selective α-cyclopropanation, whereas those generated using the Shi methodology reacted in an unexpected manner giving rise to a rearranged skeleton whereby the C ring has undergone contraction to form a novel spiro–furan ring system. Further derivatization of the cyclopropanated steroid included O-7 oxidation and epimerization to afford new bile acid derivatives for biological evaluation. Full article
(This article belongs to the Special Issue Organic Synthesis in Drug Discovery)
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14 pages, 37014 KiB  
Article
Unveiling the Reaction Mechanism of the Das/Chechik/Marek Synthesis of Stereodefined Quaternary Carbon Centers
by Pedro J. Silva and Carlos E. P. Bernardo
Appl. Sci. 2021, 11(11), 5002; https://doi.org/10.3390/app11115002 - 28 May 2021
Viewed by 2192
Abstract
The reaction mechanism of the Cu+-catalyzed introduction of two all-carbon-substituted stereocenters in an ynamide system using a Grignard reagent, a zinc carbenoid, and an aldehyde, was investigated using density-functional theory. In contrast to the formation of an organocopper(I) compound and subsequent [...] Read more.
The reaction mechanism of the Cu+-catalyzed introduction of two all-carbon-substituted stereocenters in an ynamide system using a Grignard reagent, a zinc carbenoid, and an aldehyde, was investigated using density-functional theory. In contrast to the formation of an organocopper(I) compound and subsequent carbocupration reaction, previously postulated as the initial step, the reaction proved to instead proceed through an initial complexation of the substrate alkyne bond by the Cu+-catalyst, which primes this bond for reaction with the Grignard reagent. Subsequent addition of the zinc carbenoid then enables the nucleophilic attack on the incoming aldehyde, which is revealed as the rate-limiting step. Our computations have also identified the factors governing the regio- and setereoselectivity of this interesting reaction, and suggest possible paths for its further development. Full article
(This article belongs to the Special Issue The Application of Quantum Mechanics in Reactivity of Molecules II)
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