| 12227788 |
Prashad M, Har D, Chen L, Kim HY, Repic O, Blacklock TJ: An efficient and large-scale enantioselective synthesis of PNP405: a purine nucleoside phosphorylase inhibitor. J Org Chem. 2002 Sep 20;67(19):6612-7.
An efficient and large-scale enantioselective synthesis of PNP405 (1), a purine nucleoside phosphorylase inhibitor, is described. This synthesis of 1 involved eight steps starting from o-fluorophenylacetic acid with a 21.6% overall yield and > 99.5% enantiopurity. The key stereogenic center with (R)-configuration was created using Evans' asymmetric alkylation methodology. This synthesis also features the racemization-free reductive removal of the chiral auxiliary in 5 using sodium borohydride, protection of the gamma-cyano alcohol 6 as the trityl ether by a new water-assisted tritylation with trityl chloride and triethylamine or with trityl alcohol and catalytic trifluoroacetic acid, and an efficient one-pot cyclo-guanidinylation of 10 using cyanamide as the guanidinylating agent. |
2(0,0,0,2) |