Synthesis And Crytal Structure Of Telaprevir

The total synthesis of telaprevir with six stereocentres, a highly selective and potent inhibitor of the HCV NS3-4A serine protease, has been completed through a concise synthetic route starting from the readily commercial-available compounds 2.2,2.11 and 2.9 in 4 steps with 63% overall yield.The convergent synthesis featured CuCl2-catalyzed peptide chemistry, mild hydrolysis, standard peptide chemistry reaction, and oxidation with DMP. The approach was of significant advantage in terms of reaction scale, reproducibility, and intermediate stability as well as excellent diastereoselectivity. The structure of synthetic telaprevir was validated by X-ray crystallographic analysis. Telaprevir crystallizes from a dichloromethane/ethyl acetate mixture in the orthorhombic space group P212121 with eight molecules in the unit cell. The unit cell parameters are:a= 10.5940(2) A, b= 19.4119(4) A, c= 37.6217(7) A; ?= 90°, ?= 90°, ?= 90° and V= 7736.9(3) A3. The intermolecular and intramolecular hydrogen bonds result in the stabilized helical chains crystal structure in this hybrid peptide compound.The study was done to contribute to understanding the properties of the drug at a molecular level, thus providing tools to develop novel formulations of the drug.