Synthesis of [C-11]all-trans-retinoic acid via an alkenylboron precursor by Pd(0)-mediated rapid C-[C-11]methylation

Retinoids are a class of chemical compounds which include both natural dietary vitamin A (retinol) metabolites and active synthetic analogs. Both experimental and clinical studies have revealed that retinoids regulate a wide variety of essential biological processes. In this study, we synthesized C-11-labeled all-trans-retinoic acid (ATRA), the most potent biologically active metabolite of retinol and used in the treatment of acute promyelocytic leukemia. The synthesis of C-11-labeled ATRA was accomplished by a combination of rapid Pd(0)-mediated C-[C-11]methylation of the corresponding pinacol borate precursor prepared by 8 steps and hydrolysis. [C-11]ATRA will prove useful as a PET imaging agent, particularly for elucidating the improved therapeutic activity of ATRA (natural retinoid) for acute promyelocytic leukemia by comparing with the corresponding PET probe [C-11]Tamibarotene (artificial retinoid). (C) 2014 Elsevier Ltd. All rights reserved.