Direct conversion of amino acids to oxetanol bioisosteres via photoredox catalysis.

Autor:	Delos Reyes AMV; Pharmacology Graduate Program, Weill Cornell Graduate School of Medical Sciences, Memorial Sloan Kettering Cancer Center New York New York 10065 USA tand@mskcc.org.; Chemical Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center New York New York 10065 USA., Nieves Escobar CS; Tri-Institutional PhD Program in Chemical Biology, Memorial Sloan Kettering Cancer Center New York New York 10065 USA.; Chemical Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center New York New York 10065 USA., Muñoz A; Chemical Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center New York New York 10065 USA., Huffman MI; Chemical Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center New York New York 10065 USA.; Tri-Institutional Chemical Biology Summer Program, Memorial Sloan Kettering Cancer Center New York New York 10065 USA., Tan DS; Pharmacology Graduate Program, Weill Cornell Graduate School of Medical Sciences, Memorial Sloan Kettering Cancer Center New York New York 10065 USA tand@mskcc.org.; Tri-Institutional PhD Program in Chemical Biology, Memorial Sloan Kettering Cancer Center New York New York 10065 USA.; Chemical Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center New York New York 10065 USA.; Tri-Institutional Chemical Biology Summer Program, Memorial Sloan Kettering Cancer Center New York New York 10065 USA.; Tri-Institutional Research Program, Memorial Sloan Kettering Cancer Center New York New York 10065 USA.
Jazyk:	angličtina
Zdroj:	Chemical science [Chem Sci] 2023 Sep 15; Vol. 14 (38), pp. 10524-10531. Date of Electronic Publication: 2023 Sep 15 (Print Publication: 2023).
DOI:	10.1039/d3sc00936j
Abstrakt:	Carboxylic acids are an important structural feature in many drugs, but are associated with a number of unfavorable pharmacological properties. To address this problem, carboxylic acids can be replaced with bioisosteric mimics that interact similarly with biological targets but avoid these liabilities. Recently, 3-oxetanols have been identified as useful carboxylic acid bioisosteres that maintain similar hydrogen-bonding capacity while decreasing acidity and increasing lipophilicity. However, the installation of 3-oxetanols generally requires multistep de novo synthesis, presenting an obstacle to investigation of these promising bioisosteres. Herein, we report a new synthetic approach involving direct conversion of carboxylic acids to 3-oxetanols using a photoredox-catalyzed decarboxylative addition to 3-oxetanone. Two versions of the transformation have been developed, in the presence or absence of CrCl 3 and TMSCl cocatalysts. The reactions are effective for a variety of N -aryl α-amino acids and have excellent functional group tolerance. The Cr-free conditions generally provide higher yields and avoid the use of chromium reagents. Further, the Cr-free conditions were extended to a series of N , N -dialkyl α-amino acid substrates. Mechanistic studies suggest that the Cr-mediated reaction proceeds predominantly via in situ formation of an alkyl-Cr intermediate while the Cr-free reaction proceeds largely via radical addition to a Brønsted acid-activated ketone. Chain propagation processes provide quantum yields of 5 and 10, respectively. Competing Interests: There are no conflicts to declare. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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