MACROLIDES, STEROIDS, PROSTANOIDS: SYNTHETIC DESIGNS

该计划的目的是展示适用性和发展 新的合成原理和反应的有机化学问题 与化疗重要化合物有关。 新航线 开发将导致大环化合物，前列腺素， 类固醇、β-内酰胺抗生素和相关系统。 使用 过渡金属模板作为“化学家的酶”来行使 化学选择性、区域选择性和立体控制， 相对意义是这一建议的一个主要方面。 大环 包括与红霉素相关的广谱抗生素和 多烯抗真菌化合物的阿替西菌素型。 的全碳 具有抗肿瘤活性的大环化合物的代表为 Aspochalasin。 手性合成与立体化学的创造 构象非刚性系统（即，非循环的）代表主要的 前列腺素类（广泛的临床 应用）和维生素D代谢物，在骨质疏松症的潜在用途。 新的键形成反应也将解决印防己毒素中的问题， 神经递质抑制剂和广谱β-内酰胺抗生素。

The aim of this program is to demonstrate the applicability and development of new synthetic principles and reactions to problems in organic chemistry related to chemotherapeutically important compounds. The new routes developed will lead to practical approaches to macrocycles, prostanoids, steroids, Beta-lactam antibiotics, and related systems. The use of transition metal templates as the "chemist's enzymes" to exercise chemoselectivity, regioselectivity, and stereocontrol in an absolute and relative sense constitutes a major aspect of this proposal. Macrolides include the broad spectrum antibiotics related to the erythromycins and the polyene antifungal compounds of the amphotericin type. An all carbon macrocycle that possesses antitumor activity is represented by aspochalasin. Chiral synthesis and creation of stereochemistry in conformationally non-rigid systems (ie. acyclic ones) represent major aspects of the proposed strategies to prostanoids (of broad clinical application) and Vitamin D metabolites, of potential use in osteoporosis. New bond forming reactions will also address problems in picrotoxins, neurotransmitter inhibitors, and broad spectrum Beta-lactam antibiotics.