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 (LiCH2Cl), 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.

Merging lithium carbenoid homologation and enzymatic reduction: A combinative approach to the HIV-protease inhibitor Nelfinavir / L. Castoldi, L. Ielo, P. Hoyos, M.J. Hernaiz, L. De Luca, A.R. Alcantara, W. Holzer, V. Pace. - In: TETRAHEDRON. - ISSN 0040-4020. - 74:18(2018 May 03), pp. 2211-2217. [10.1016/j.tet.2018.03.034]

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

L. Castoldi
Primo
;
2018

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 (LiCH2Cl), 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.
a-haloketones; Drug Synthesis; Enzymatic reductions; Halohydrins; Homologation; Lithium carbenoids; Selectivity;
Settore CHIM/06 - Chimica Organica
15-mar-2018
Article (author)
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S0040402018302771-main.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 657.41 kB
Formato Adobe PDF
657.41 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/890727
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 20
  • ???jsp.display-item.citation.isi??? 19
social impact