An efficient, diversity oriented synthesis of homoisoprenoid α-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 α-monofluoromethylene moiety.
|Number of pages||4|
|Journal||Bioorganic and Medicinal Chemistry Letters|
|State||Published - Sep 15 2014|
Bibliographical noteFunding Information:
We thank Drs. Jing Chen and Haining Zhu for assistance obtaining some of the mass spectra. This work was supported by NIH grants R01 GM66152 to H.P.S., R01 GM50388 , P20 GM103527 and with resources provided by the Lexington Veterans Affairs Medical Center to A.J.M.
© 2014 Elsevier Ltd. All rights reserved.
- Farnesyl diphosphate
- Mevalonate pathway
- Phosphatase inhibitor
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry