Development of Efficient and Selective Synthetic Routes to Bio-active Compounds Using Reductive Method with Novel Redox Systems

在氧化还原反应的基础上发展了一种新的合成方法，这些方法适用于关键反应或为生物活性化合物的合成提供了一条新的途径。1)通过还原去共轭反应开发了一条合成Patuolide A的新路线，该路线也被应用于含有β，γ-不饱和羰基或γ-氧代(或羟基)α，β-不饱和羰基的衍生物的系统合成。2)有效地利用过渡金属的单电子还原，可以开发新的自由基反应合成方法。GEM-二溴环丙烷与低价钒物种进行了基于单电子还原的高立体选择性的单脱溴反应。研究发现，在锌作为化学计量比共还原剂存在的情况下，该反应是催化进行的。二乙基膦酸根的存在对于这种转化是必不可少的。低价稀有金属具有还原GEM-二溴环丙烷的能力。3)采用催化片呐醇偶联的方法合成了一种有效的酶抑制剂A-77003。环戊二烯取代的钒化合物在化学计量比的氯硅烷和锌作为助还原剂的存在下，能够作为这样的催化剂。使用四氢呋喃作为溶剂得到了所需的二元醇，这与二甲氧基乙烷中二氧杂环戊烷的形成形成了对比。这一发现为还原偶联提供了一种有效的方法，因为使用钛催化剂只能生成二氧环己烷。非对映选择性依赖于起始醛的空间效应。高dl非对映选择性是在钒催化的空间大体积脂肪醛的片呐醇偶联反应中实现的。

Novel synthetic methods, which are applicable to key reactions or provide a new route for the synthesis of bio-active compounds, have been developed on the basis of redox reactions.1) A new route to Patuolide A has been developed by using reductive deconjugation, which was also applied to the systematic synthesis of their derivatives bearing beta, gamma-unsaturated carbonyl group or gamma-oxo-(or hydroxy-) alpha, beta-unsaturated carbonyl group.2) Efficient usage of one-electron reduction with transition metals is considered to permit the development of novel synthetic method for radical reactions. gem-Dibromocyclopropanes underwent the highly stereoselective monodebromination based on one-electron reduction with low valent vanadium species. The reaction was found to proceed catalytically in the presence of zinc as a stoichiometric co-reductant. The presence of diethyl phosphonate is essential for this transformation. Low valent rare metals were capable of reducing gem-dibromocyclopropanes.3) An efficent process for the synthesis of Protease Inhibitor A-77003 is allowed by catalytic pinacol coupling. Cyclopentadienyl-substituted vanadium compounds were able to serve as such a catalyst in the presence of a stoichiometric amount of chlorosilane and zinc as a co-reductant. Use of THF as a solvent gave the desired diols, being in contrast to the formation of dioxolanes in dimethoxyethane. This finding provided an eficient method for reductive coupling since only dioxolane was produced by using the titanium catalyst. The diastereoselectivity depended on the steric effect of the starting aldehydes. The high dl diastereoselectivity was achieved in the vanadium-catalyzed pinacol coupling of sterically bulky aliphatic aldehydes.