A domino Kornblum-DeLaMare/aza-Michael reaction of 3,6-dihydro-1,2-dioxines and application to the synthesis of the ceramide transport inhibitor (+/-)-HPA-12

摘要

A Kornblum-DeLaMare/aza-Michael reaction of 3,6-dihydro-1,2-dioxines with primary and secondary amines has been developed which affords 4-hydroxy-3-aminoketones. The aza-Michael products were reduced using non-selective NaBH4/MeOH or diastereoselective (up to 92:8) SnCl4/NaBH4 conditions yielding (1R*,3S*)-3-amino-1,4-diols in up to 97% and 70% yield respectively. The major reduction product was converted in two steps to (+/-)-HPA-12, which is an inhibitor of the cytosolic ceramide transporting protein. (C) 2017 Elsevier Ltd. All rights reserved.