Shoji Mitsuru, Imai Hiroki, Mukaida Makoto, Sakai Ken, Kakeya Hideaki, Osada Hiroyuki, Hayashi Yujiro
Department of Industrial Chemistry, Faculty of Engineering, Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan.
J Org Chem. 2005 Jan 7;70(1):79-91. doi: 10.1021/jo048425h.
Full details of two versions of the total synthesis of epoxyquinols A, B, and C and epoxytwinol A (RKB-3564D) are described. In the first-generation synthesis, the HfCl(4)-mediated diastereoselective Diels-Alder reaction of furan with Corey's chiral auxiliary has been developed. In the second-generation synthesis, a chromatography-free preparation of an iodolactone, by using acryloyl chloride as the dienophile in the Diels-Alder reaction of furan, and the lipase-mediated kinetic resolution of a cyclohexenol derivative have been developed. This second-generation synthesis is suitable for large-scale preparation. A biomimetic cascade reaction involving oxidation, 6pi-electrocyclization, and then Diels-Alder dimerization is the key reaction in the formation of the complex heptacyclic structure of epoxyquinols A, B, and C. Epoxytwinol A is synthesized by the cascade reaction composed of oxidation, 6pi-electrocyclization, and formal [4 + 4] cycloaddition reactions. A 2H-pyran, generated by oxidation/6pi-electrocyclization, acts as a good diene, reacting with several dienophiles to afford polycyclic compounds in one step. An azapentacyclic compound is synthesized by a similar cascade reaction composed of the four successive steps: oxidation, imine formation, 6pi-azaelectrocyclization, and Diels-Alder dimerization.
本文描述了环氧喹诺醇A、B、C以及环氧孪醇A（RKB - 3564D）两种全合成版本的详细信息。在第一代合成中，开发了HfCl(4)介导的呋喃与科里手性助剂的非对映选择性狄尔斯-阿尔德反应。在第二代合成中，开发了一种无需柱色谱的碘内酯制备方法，即在呋喃的狄尔斯-阿尔德反应中使用丙烯酰氯作为亲双烯体，以及脂肪酶介导的环己烯醇衍生物的动力学拆分。这种第二代合成方法适用于大规模制备。涉及氧化、6π-电环化，然后是狄尔斯-阿尔德二聚化的仿生级联反应是形成环氧喹诺醇A、B和C复杂七环结构的关键反应。环氧孪醇A是通过由氧化、6π-电环化和形式上的[4 + 4]环加成反应组成的级联反应合成的。由氧化/6π-电环化生成的2H-吡喃作为良好的双烯，与几种亲双烯体反应一步得到多环化合物。一种氮杂五环化合物是通过由氧化、亚胺形成、6π-氮杂电环化和狄尔斯-阿尔德二聚化这四个连续步骤组成的类似级联反应合成的。
