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Natural products are useful sources in the search for biochemical probes and drug leads because of their unique biological activities. However, synthetic studies or functional analyses of polycyclic complex natural products or conjugated lipids (e.g., glycolipids) are often hampered because of their synthesis and handling are challenging. On the basis of rational designs, synthetic studies, and chemical modifications, natural products need to be optimized to more potent compounds with improved activities, selectivities and/or physical properties. We have been synthesizing natural products and their derivatives for the elucidation of their biological mechanisms and discovery of drug leads. This review describes three topics for developing functional compounds derived from natural products for prospective involvement in pharmaceutical research: 1) direct construction of the ergot alkaloid scaffold by palladium catalyzed domino cyclization of amino allenes; 2) identification of novel sphingosine kinase inhibitors through a structure-activity relationship study of jaspine B; and 3) design, synthesis and biological evaluation of novel CD1d glycolipid ligands containing modified lipid moieties.

Due to the advent of multi-drug therapy (MDT) recommended by the WHO, for the treatment of leprosy, presently, leprosy is regarded as a "curable disease". The number of new cases in Japan is relatively very low, due to which the disease is likely to be neglected, but on scientific grounds, there is a necessity to perform in depth studies. Leprosy caused by M. leprae is still unclear on various aspects including transmission, immunology, nerve damage etc. Here we introduce the recent advances in the field of basic leprosy research.

Trehalose dimycolate (TDM) is a glycolipid contained in the cell walls of Mycobacteria, Nocardia and Corynebacteria. An intraperitoneal injection of TDM into mice has been known to produce hemorrhagic pneumonia without affecting any other organs. Thus, it provides a unique experimental model for studies of the mechanisms of alveolar hemorrhagic syndrome, including idiopathic pulmonary hemosiderosis. It has been reported that T lymphocytes are essential for the production of TDM-induced hemorrhagic pneumonia, however, the overall cellular mechanism is not yet clear. The purpose of this study is to re-examine and clarify the role of T lymphocytes in the pathogenesis of TDM-induced hemorrhagic pneumonia. To achieve it we considered 1) the dynamics of infiltrating lymphocytes to find out if there is a certain T lymphocyte subpopulation infiltrating predominantly into the lung, 2) the effect of in vivo depletion of T lymphocyte subpopulation by monoclonal antibodies, and 3) the effect of transfer of T lymphocytes into nude mice. The analysis of the dynamic change of the number of lymphocytes showed that the number of L3T4+ cells as well as Lyt2+ cells decreased on day 2 or 3 after TDM injection, thereafter increased, however, neither subpopulation infiltrated predominantly into the lung. Alveolar hemorrhages occurred in L3T4+ cell-depleted and/or Lyt2+ cell-depleted mice, and hemorrhages were enhanced in Lyt2+ cell-deplete mice. Alveolar hemorrhages occurred even in nude mice, and the intensity of hemorrhages or the cell numbers in the lung did not differ from those in T lymphocyte-reconstituted nude mice, however, hemorrhages were enhanced in L3T4+ cell-reconstituted nude mice. These results suggested that T lymphocytes are not primarily involved in the cellular mechanisms of the pathogenesis of TDM-induced hemorrhagic pneumonia, however, L3T4+ cells modify the process of the production of hemorrhagic pneumonia secondarily and enhance it.