An Inexpensive and Scalable Synthesis of Shld

The Journal of Organic Chemistry
Frederik Præstholm Jørgensen, Mikael Bols

Abstract

A synthesis of the important FKBP ligand Shld is reported. The synthesis avoids stoichiometric use of expensive and chiral reagents, maintains enantioselectivity and provides a high overall yield (39%). The main features in the method are enantioselective alkylation for preparation of the phenyl acetic acid moiety (building block A), catalytic enantioselective reduction for obtaining the chiral diaryl-1-propanol (building block C), and direct acylation of S-pipecolic tartrate rather than use of expensive Fmoc-pipecolic acid. The assembly of the building blocks A-C is reversed in comparison to previous synthesis, which also eliminates the need for protective groups.

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Citations

Dec 21, 2018·Frontiers in Pharmacology·Jürgen M KolosFelix Hausch
Mar 6, 2021·Journal of Medicinal Chemistry·Michael BauderFelix Hausch
Apr 13, 2021·Angewandte Chemie·Andreas M VollFelix Hausch
Dec 31, 2020·ACS Central Science·Vedagopuram SreekanthAmit Choudhary
Feb 7, 2020·ACS Combinatorial Science·Daniel MadsenMorten Meldal

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