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Preparation of a Key Intermediate En Route to the Anti-HIV Drug Lenacapavir.

ABSTRACT: A very efficient four-step synthesis of the main fragment of Gilead's anti-HIV drug lenacapavir is described. The route showcases a 1,2-addition to an intermediate aldehyde using an organozinc halide derived from a commercially available difluorobenzyl Grignard reagent. This sets the stage for the oxidation of the resulting secondary alcohol to the desired ketone, which relies solely on catalytic amounts of TEMPO together with NaClO as the terminal oxidant, affording the targeted ketone in 67% overall yield.

SUBMITTER: Caravez JC

PROVIDER: S-EPMC10949239 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Preparation of a Key Intermediate En Route to the Anti-HIV Drug Lenacapavir.

Caravez Juan C JC Hu Yuting Y Oftadeh Erfan E Mamo Kirubel T KT Lipshutz Bruce H BH

The Journal of organic chemistry 20240306 6

A very efficient four-step synthesis of the main fragment of Gilead's anti-HIV drug lenacapavir is described. The route showcases a 1,2-addition to an intermediate aldehyde using an organozinc halide derived from a commercially available difluorobenzyl Grignard reagent. This sets the stage for the oxidation of the resulting secondary alcohol to the desired ketone, which relies solely on catalytic amounts of TEMPO together with NaClO as the terminal oxidant, affording the targeted ketone in 67% o ...[more]

PMID: 38447077

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