SYNTHESIS OF NOVEL BIOLOGICALLY ACTIVE NATURAL PRODUCTS

这项资助将在三个主要领域进行研究：1)完成降糖药Saudin的全合成工作(1)；试验1及其前体，以识别药效团，并确定是否可能引起降糖作用的机制（与山德士研究所合作）；根据先前的研究准备适当的类似物；2)继续研究应用Lewis酸催化的不对称[2+2]环加成反应和不对称SN2'取代反应作为获得手性乙烯基环丁烷前体(+)-Laurenyne(2)和(+)-Laurenyne(3)的一般方法。采用新颖的反克莱森重排，以对映体纯形式创建所需的氧新世环体系。3)研究了新型TiC14催化内环乙烯基烯丙基醚Claisen重排的机理、范围和局限性。这一过程允许修改相对于热重排过程的立体化学结果。关于适当配置氧功能的内部螯合物允许将环构象从半椅型修改为半船型的假设将进行测试。

The studies to be conducted under this grant fall in three major areas: 1) complete work on the total synthesis of the hypoglycemic agent Saudin (1); test 1 and its precursors to identify the pharmacophore, and determine if possible the mechanism by which the hypoglycemic effects are elicited (in collaboration with Sandoz Research Institute); prepare appropriate analogues as warranted by the preceding studies; 2) continue work directed at the application of Lewis acid catalyzed asymmetric [2+2] cycloaddition reactions and asymmetric SN2' substitutions as general methods to access the chiral vinylcyclobutane precursors for (+)-Laurencin (2) and (+)-Laurenyne (3). To employ the novel retro-Claisen rearrangement to create the required oxocene ring system in enantiomerically pure form. 3) investigate the mechanism, scope, and limitations of the novel TiC14 catalyzed Claisen rearrangement of endocyclic vinyl allyl ethers. This process permits modification of the stereochemical outcome of the process relative to the thermal rearrangement. The hypothesis that an internal chelate of suitably disposed oxygen functions permits the modification of the ring conformation from half-chair to half-boat will be tested.