Design and synthesis of non-hydrolyzable homoisoprenoid alpha-monofluorophosphonate inhibitors of PPAPDC family integral membrane lipid phosphatases

摘要

An efficient, diversity oriented synthesis of homoisoprenoid alpha-monofluorophosphonates utilizing electrophilic fluorination is presented along with their activity as inhibitors of PPAPDC2 family integral membrane lipid phosphatases. These novel phosphatase-resistant analogues of isoprenoid monophosphates are a platform for further structure-activity relationship studies and provide access to other isoprenoid family members where the phosphate ester oxygen is replaced by a alpha-monofluoromethylene moiety. (C) 2014 Elsevier Ltd. All rights reserved.