Natural product synthesis and development of synthetic methodology

该研究计划涉及(1)几个生物学上重要和复杂的天然产物的全合成计划，以及处理这些化合物所带来的结构问题的新合成方法的发展，以及(2)应该广泛适用于一系列目标物质的通用合成方法的发展。主要天然产物是(1)CP-225,917，一种抗癌和降胆固醇物质；(2)玛利诺吡咯B，一种前所未有的抗生素；(3)色素素B，一种参与细菌细胞壁合成的酶的抑制剂；(4)山梨酸内酯A，具有选择性抗白血病活性，同时具有抗病毒（HIV）和神经保护作用；(5) MPC1001，其对前列腺癌细胞系表现出非常强大的活性。这些天然产物，除了具有使其成为重要合成目标的生物学特性外，还会带来普遍存在的结构问题，这些问题的解决方案将填补当前技术的空白。针对这些靶分子，将研究生成吡咯、大内酰胺和三羰基化合物的新途径。

The research proposal deals with (1) plans for the total synthesis of several biologically important and complex natural products and with the development of new synthetic methodology to deal with the constructional problems posed by these compounds, and (2) the development of general synthetic methods that should have wide applicability to a range of target substances. The main natural products are (1) CP-225,917, an anticancer and cholesterol-lowering substance; (2) marinopyrrole B, an unprecedented class of antibiotic; (3) coleophomone B, an inhibitor of an enzyme involved in bacterial cell wall synthesis; (4) sorbicillactone A, which shows selective anti-leukemic activity, and also has antiviral (HIV) and neuroprotective properties; and (5) MPC1001, which exhibits very powerful activity against a prostate cancer cell line. These natural products, besides having biological properties that identify them as important synthetic targets, also pose constructional problems that are of general occurrence and the solution to these problems will fill gaps in current technology. In relation to these target molecules, new routes to pyrroles, macrolactams and tricarbonyl compounds will be studied.