First synthesis and determination of the absolute configuration of sulphostin, a novel inhibitor of dipeptidyl peptidase IV

Journal of Natural Products
Masatoshi AbeYasuhiko Muraoka

Abstract

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.

References

Jul 15, 1978·FEBS Letters·E Heymann, R Mentlein
Jan 1, 1997·International Journal of Immunopharmacology·S TanakaT Sugita
Nov 21, 2001·The Journal of Antibiotics·T AkiyamaT Takeuchi

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Citations

Jun 25, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Birgit WaltenbergerAtanas G Atanasov
Sep 20, 2017·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Christopher J Benway, John Iacomini
Apr 20, 2005·The Journal of Antibiotics·Masatoshi AbeTetsushi Saino
Mar 5, 2016·Acta Crystallographica. Section C, Structural Chemistry·Mojtaba KeikhaArie van der Lee
Jan 27, 2021·Chemistry : a European Journal·Shinichiro FuseHiroyuki Nakamura
Jan 25, 2018·Journal of Natural Products·Janusz J PetkowskiSara Seager

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