Isotopically labeled compounds have numerous applications in drug discovery and development. (R)-9-(2-Hydroxypropyl)adenine 1 is an important intermediate in the synthesis of various acyclic nucleoside phosphonates including tenofovir. We have developed a short synthetic method to prepare deuterium and tritium labeled 1 using a ketoreductase enzyme catalyzed reduction as the key step to introduce the label in a highly efficient and enantioselective way. (C) 2016 Elsevier Ltd. All rights reserved.
Enzymatic approach toward the synthesis of isotopically labeled (R)-9-(2-hydroxypropyl)adenine