SYNTHESIS OF LEUCONOLIDE VIA BORONIC ESTERS

我们最新发现的基于硼酸的不对称合成方法 酯化学将应用于亮康内酯的合成 大环内酯类抗生素白霉素的苷元。所有七个手性中心 可以通过手性二醇的硼酸酯的反应来构建 使用(二卤甲基)锂，它将CHX基团插入碳- 具有99%绝对构型控制的硼键。硼促进了 邻近的卤化物被各种亲核试剂取代， 在这一过程中的动力学解析提供了额外的改进 已经非常出色的非对讲机选拔。计划中的合成构建 分子分为三个主要部分，其中两个部分将由一个 卤代硼酸酯与烷氧基锂的立体专一性偶联 从另一种硼酸酯衍生的试剂。剩余的细分市场将是 卤化乙烯的一端酯化和铃木偶联 在另一端提供二烯。酯化反应是 已经被认为是大环内酯封闭的一种手段。铃木二烯的合成 也将作为关闭环的一种手段进行测试。这种新的化学物质提供了 错综复杂化合物高效控制合成的重大机遇 手性结构，如亮内酯或其他大环内酯或离子载体 抗生素。

Our recently discovered method of asymmetric synthesis based on boronic ester chemistry will be applied to the synthesis of leuconolide, the aglycone of the macrolide antibiotic leucomycin. All seven chiral centers can be constructed via the reaction of a boronic ester of a chiral diol with a (dihalomethyl)lithium, which inserts a CHX group into the carbon- boron bond with >99% control of absolute configuration. Boron facilitates the displacement of the neighboring halide by a variety of nucleophiles, and kinetic resolution during this process provides additional improvement of the already excellent diastereoselection. The planned synthesis builds the molecule in three major segments, and two of these will be joined by a stereospecific coupling of halo boronic ester with an alkoxy lithium reagent derived from another boronic ester. The remaining segment will be connected via esterification at one end and Suzuki coupling of vinyl halide to boronic ester to provide the diene at the other. The esterification is already known as a means of macrolide closure. The Suzuki diene synthesis will also be tested as a means of ring closure. This new chemistry offers a major opportunity for the efficient controlled synthesis of intricate chiral structures such as leuconolide or other macrolide or ionophore antibiotics.