An effective stereocontrolled synthesis of the HIV protease inhibitor Nelfinavir is reported. Two transformations were identified crucial for achieving success: the formation of a densely functionalized alpha-chloroketone via the homologation of a Weinreb amide with chloromethyllithium (LiCH2Cl), followed by its erythro selective reduction into the corresponding chiral chlorohydrin. A commercially available enzyme P2-CO2 was particularly well suited for this purpose, affording the key alcohol (in an excellent 99% de), which was then smoothly converted into the active biologically active agent.

Merging lithium carbenoid homologation and enzymatic reduction: A combinative approach to the HIV-protease inhibitor Nelfinavir

Ielo, Laura
Secondo
;
De Luca, Laura;
2018-01-01

Abstract

An effective stereocontrolled synthesis of the HIV protease inhibitor Nelfinavir is reported. Two transformations were identified crucial for achieving success: the formation of a densely functionalized alpha-chloroketone via the homologation of a Weinreb amide with chloromethyllithium (LiCH2Cl), followed by its erythro selective reduction into the corresponding chiral chlorohydrin. A commercially available enzyme P2-CO2 was particularly well suited for this purpose, affording the key alcohol (in an excellent 99% de), which was then smoothly converted into the active biologically active agent.
2018
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/3126089
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