The main objective of the proposed research is to provide new and innovative synthetic methods that are applicable to efficient and selective syntheses of a wide variety or complex natural products and related organic compounds including those of medicinal and biological interest through development of organotransition metal chemistry, especially of palladium and zirconium. Methodological development during the proposed research period will be focused on (1) cross-coupling, (2) carbometallation and hydrometallation, (3) carbonylation and other migratory insertion reactions and (4) oxy- and aminometallation. Special emphasis will be placed on the development of synthetic protocols involving combined uses of (1) - (4), especially (1) and (2), In the proposed research, it is essential to have a research program and system in which methodological developments reciprocally interact with applications to the synthesis of natural products and related target molecules. Most of the target molecules in the proposed research are selected from this viewpoint, and execution of their synthesis primarily from this viewpoint constitutes the second main objective. In some select cases, however, efforts will be made to synthesize compounds of medicinal interest and provide their samples. This then is the third main objective of the proposed research. Both methodological developments and target syntheses will be performed in the following five areas: (1) conjugated oligoenes of defined stereo- and regiechemistry including carotenoids, oligoene macrolide antibiotics, and others, e.g., stipiamide and amphotericin B, (2) oligoenes containing 1,5- and 1,4-diene units including coenzymes Qn, where n is an integer, such as 3, 4, 9, 10, and so on, and other isoprenoids, e.g., mycolactones A and B, (3) chiral aliphatic chain-containing natural products and related compounds, e.g., scyphostatin and fluvircinine A, (4) bi- and oligocarbocycles obtainable via cyclic carbopalladation and acylpalladation, e.g., nagilactone F, and (5) heterocycles preparable via cross-coupling, carbonylation, and oxymetallation or aminometallation. As new and attractive targets become known in the literature, some such targets will also be selected and synthesized. This would necessitate omission of some of the proposed targets and/or deferment of their synthesis as well as deletion, addition, and/or modification of research topics to maximize PI's research contributions within the general areas of the proposed research.
Showing the most recent 10 out of 11 publications
