Total Synthesis of Eliglustat via Diastereoselective Amination of Chiral para-Methoxycinnamyl Benzyl Ether

Autor:	Younggyu Kong, Pulla Reddy Boggu, Gi Min Park, Yeon Su Kim, Seong Hwan An, In Su Kim, Young Hoon Jung
Jazyk:	angličtina
Rok vydání:	2022
Předmět:	amination eliglustat chlorosulfonyl isocyanate Sharpless asymmetric dihydroxylation total synthesis Organic chemistry QD241-441
Zdroj:	Molecules, Vol 27, Iss 8, p 2603 (2022)
Druh dokumentu:	article
ISSN:	1420-3049
DOI:	10.3390/molecules27082603
Popis:	Eliglustat (Cerdelga®, Genzyme Corp. Cambridge, MA, USA) is an approved drug for a non-neurological type of Gaucher disease. Herein, we describe the total synthesis of eliglustat 1 starting from readily available 1,4-benzodioxan-6-carbaldehyde via Sharpless asymmetric dihydroxylation and diastereoselective amination of chiral para-methoxycinnamyl benzyl ethers using chlorosulfonyl isocyanate as the key steps. Notably, the reaction between syn-1,2-dibenzyl ether 6 and chlorosulfonyl isocyanate in the mixture of toluene and hexane (10:1) afforded syn-1,2-amino alcohol 5 at a 62% yield with a diastereoselectivity > 20:1. This observation can be explained by competition between the SNi and the SN1 mechanisms, leading to the retention of stereochemistry.
Databáze:	Directory of Open Access Journals
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