307345-39-7Relevant articles and documents
Development of a large-scale synthesis of sulphostin, a dipeptidyl peptidase IV inhibitor
Abe, Masatoshi,Nagai, Masashi,Yamamoto, Keiichiro,Yamazaki, Hiroko,Koga, Ichiro,Satoh, Yoshitaka,Muraoka, Yasuhiko,Kurashige, Shuji,Ichikawa, Yuh-Ichiro
, p. 570 - 576 (2005)
For the progress of the in vivo study on sulphostin, a dipeptidyl peptidase IV inhibitor, its large-scale synthetic method was investigated. The optical resolution of (3S,RSP)-1-amino(sulfoamino)phosphinyl-3- benzyloxycarbonylamino-2-piperidinone, which was the most difficult step in the previous method, was simplified by using fractional crystallization. The use of 2 mol equiv of (1S,2R)-(+)-2-amino-1,2-diphenylethanol for optical resolution gave desired diastereomer 15 in good yield as a less soluble salt. In the present synthetic method, there were no requirements for purification using column chromatography, reaction at cryogenic temperature, and treatment using the haloalkane solvents. The total yield of the new method was 4.6%, which was an improvement of approximately 2-fold compared to the method reported previously.
First synthesis and determination of the absolute configuration of sulphostin, a novel inhibitor of dipeptidyl peptidase IV
Abe, Masatoshi,Akiyama, Tetsuo,Nakamura, Hikaru,Kojima, Fukiko,Harada, Shigeko,Muraoka, Yasuhiko
, p. 999 - 1004 (2007/10/03)
Sulphostin, a novel dipeptidyl peptidase IV (DPP-IV) inhibitor, was isolated from the culture broth of Streptomyces sp. MK251-43F3. Determination of the absolute configurations of two asymmetric atoms using the natural product was not achieved due to the small amount of the compound obtained. We synthesized four possible stereoisomers of sulphostin from D- or L-ornithine and compared their physicochemical and biological data to naturally isolated sulphostin. As a result, the absolute configurations at C-3 and the phosphorus atom of sulphostin were determined to be S and R, respectively, by X-ray crystallography. Synthetic sulphostin and its C-3 epimer have strong inhibitory activities against DPP-IV, IC50 values of which are 6.0 and 8.9 ng/mL, respectively. Thus it appears that the configuration of the phosphorus atom is primarily responsible for the activity; in contrast, the configuration of C-3 does not appear to affect the activity.
