Strain-Release Heteroatom Functionalization: Development, Scope, and Stereospecificity.

Autor:	Lopchuk JM; Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States., Fjelbye K; Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States., Kawamata Y; Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States., Malins LR; Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States., Pan CM; Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States., Gianatassio R; Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States., Wang J; Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States., Prieto L; Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States., Bradow J; Pfizer Worldwide Research and Development , Eastern Point Road, Groton, Connecticut 06340, United States., Brandt TA; Pfizer Worldwide Research and Development , Eastern Point Road, Groton, Connecticut 06340, United States., Collins MR; Department of Chemistry, La Jolla Laboratories, Pfizer Inc. , 10770 Science Center Drive, San Diego, California 92121, United States., Elleraas J; Department of Chemistry, La Jolla Laboratories, Pfizer Inc. , 10770 Science Center Drive, San Diego, California 92121, United States., Ewanicki J; Department of Chemistry, La Jolla Laboratories, Pfizer Inc. , 10770 Science Center Drive, San Diego, California 92121, United States., Farrell W; Department of Chemistry, La Jolla Laboratories, Pfizer Inc. , 10770 Science Center Drive, San Diego, California 92121, United States., Fadeyi OO; Pfizer Worldwide Research and Development , Eastern Point Road, Groton, Connecticut 06340, United States., Gallego GM; Department of Chemistry, La Jolla Laboratories, Pfizer Inc. , 10770 Science Center Drive, San Diego, California 92121, United States., Mousseau JJ; Pfizer Worldwide Research and Development , Eastern Point Road, Groton, Connecticut 06340, United States., Oliver R; Pfizer Worldwide Research and Development , Eastern Point Road, Groton, Connecticut 06340, United States., Sach NW; Department of Chemistry, La Jolla Laboratories, Pfizer Inc. , 10770 Science Center Drive, San Diego, California 92121, United States., Smith JK; Pfizer Worldwide Research and Development , Eastern Point Road, Groton, Connecticut 06340, United States., Spangler JE; Department of Chemistry, La Jolla Laboratories, Pfizer Inc. , 10770 Science Center Drive, San Diego, California 92121, United States., Zhu H; Department of Chemistry, La Jolla Laboratories, Pfizer Inc. , 10770 Science Center Drive, San Diego, California 92121, United States., Zhu J; Department of Chemistry, La Jolla Laboratories, Pfizer Inc. , 10770 Science Center Drive, San Diego, California 92121, United States., Baran PS; Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Jazyk:	angličtina
Zdroj:	Journal of the American Chemical Society [J Am Chem Soc] 2017 Mar 01; Vol. 139 (8), pp. 3209-3226. Date of Electronic Publication: 2017 Feb 20.
DOI:	10.1021/jacs.6b13229
Abstrakt:	Driven by the ever-increasing pace of drug discovery and the need to push the boundaries of unexplored chemical space, medicinal chemists are routinely turning to unusual strained bioisosteres such as bicyclo[1.1.1]pentane, azetidine, and cyclobutane to modify their lead compounds. Too often, however, the difficulty of installing these fragments surpasses the challenges posed even by the construction of the parent drug scaffold. This full account describes the development and application of a general strategy where spring-loaded, strained C-C and C-N bonds react with amines to allow for the "any-stage" installation of small, strained ring systems. In addition to the functionalization of small building blocks and late-stage intermediates, the methodology has been applied to bioconjugation and peptide labeling. For the first time, the stereospecific strain-release "cyclopentylation" of amines, alcohols, thiols, carboxylic acids, and other heteroatoms is introduced. This report describes the development, synthesis, scope of reaction, bioconjugation, and synthetic comparisons of four new chiral "cyclopentylation" reagents.
Databáze:	MEDLINE
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