Reference

Potential inhibitors of collagen biosynthesis

Potential inhibitors of collagen biosynthesis. 4,4-Difluoro-L-proline and 4,4-dimethyl-DL-proline and their activation by prolyl-tRNA ligase. Shirota, Frances N.; Nagasawa, Herbert T.; Elberling, James A. (Med. Res. Lab., VA Hosp., Minneapolis, Minn., USA). J. Med. Chem., 20(9), 1176-81 (English) 1977. CODEN: JMCMAR. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacodynamics) Section cross-reference(s): 34, 7 Condensation of 4-hydroxy-L-proline Me ester-HCl [40216-83-9] with N-carbobenzoxy-4-hydroxy-L-proline [13504-85-3] followed by hydrogenolysis and spontaneous cyclization gave octahydro-2,7-dihydroxy-5H,10H-dipyrrolo[1,2-a:1',2'-d]pyrazine-5,10-di one [52363-44-7] which was oxidized, fluorinated, and hydrolyzed to give 4,4-difluoro-L-proline (II) [52683-81-5]. Reductive cyclization of 4-cyano-2,2-dimethylbutyraldehyde [6140-61-0] followed by chlorination gave 3,3-dichloro-5,5-dimethyl-2-piperidone [63624-43-1], which upon monodeclorination by hydrogenolysis and hydrolytic rearrangement gave 4,4-dimethyl-DL-proline (II) [63624-41-9]. I stimulated the ATP-inorg. pyrophosphate exchange reaction in the presence of prolyl-tRNA ligase, but the Km value was 100 times that for L-proline.Several reagents such as 63624-44-2 is used here. II was a competitive inhibitor of exchange with Ki value of 1.5 .times. 10-2M. Neither I nor II inhibited growth of P-388 lymphocytic leukemia cells. .