A Concise Synthesis of (-)-Cytoxazone via Regioselective and Stereoselective Introduction of Amino Group using Chlorosulfonyl Isocyanate

In 1998, Osada and co-workers isolated 140 mg of a novel cytokine modulator from 18 L of the culture broth of Streptomyces RK95- 31 isolated from a soil sample in Hiroshima Prefecture. This new immunosuppressant was named (-)-cytoxazone and its absolute configuration was determined on the basis of its NMR, CD and X -ray analysis. It interferes with cytokine IL4, IL10 and IgG production by selective inhibition of the signaling pathway of Th2 cells, but not Thl cells. Inhibitors of Th2-dependent cytokine production have potential as potent chemotherapeutic agents in the field of immunotherapy. The (-)-cytoxazone is different from known immunomodulators such as FK 506 and rapamycin in respect of structure and biological activity. As such cytoxazone should be a useful tool for understanding signaling pathways in Th2 cells, the synthesis of (-)-cytoxazone is of interest for the development of new cytokine modulators.