Merging lithium carbenoid homologation and enzymatic reduction: A combinative approach to the HIV-protease inhibitor Nelfinavir. Issue 18 (3rd May 2018)

• Record Type: Journal Article
• Authors: Castoldi, Laura; Ielo, Laura; Hoyos, Pilar; Hernáiz, María J.; De Luca, Laura; Alcántara, Andrés R.; Holzer, Wolfgang; Pace, Vittorio
• Is Part Of: Tetrahedron. Volume 74:Issue 18(2018)
• Page Start: 2211
• Page End: 2217
• Publication Date: 2018-05-03
• Subjects: Homologation -- Lithium carbenoids -- Enzymatic reductions -- Drug Synthesis -- a-haloketones -- Halohydrins -- Selectivity; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2018.03.034
• Languages: English
• ISSNs: 0040-4020

Abstract

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 α-chloroketone via the homologation of a Weinreb amide with chloromethyllithium (LiCH2 Cl), followed by its erythro selective reduction into the corresponding chiral chlorohydrin. A commercially available enzyme P2-C02 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. Graphical abstract: