Development of Industrial Synthetic Process Toward Prostaglandins

无论从生物学角度还是从合成角度来看，新的、实用的、高效的前列腺素合成都是非常重要的。本文所描述的新方法包括以下新工艺：(1)以二阴离子衍生琥珀酸酯为原料合成五元环体系的新工艺。(2)不对称Diels-Alder反应中协同阻挡效应的发现和利用，得到了光学纯度较高的六元环体系。(3)部分加合物转化为具有较高生物活性的前列腺素衍生物。(4)含有酒石酸酯配体的烯丙基硼酸酯对于构建前列腺素衍生物的侧链是非常有用的。(5)不对称环丙烷化反应新工艺成功应用于前列腺素类似物的合成，这些合成方法不仅适用于前列腺素衍生物的合成，而且可广泛应用于多种生物活性物质的合成。

New practical and efficient synthesis of prostaglandin is highly important both from biological as well as synthetic point of view. The new methods described herein constitute the following new process.(1) A new process for the construction of five-membered ring system starting from the dianion derived succinate esters. (2) Discovery of cooperative blocking effect and utilization of this effect for the asymmetric Diels-Alder reaction produced the six-membered ring system of high optical purities. (3) some of the adducts was transformed to the prostaglandin derivative which is found to be biologically highly active. (4) Allenylboronic ester with tartaric ester ligands was shown to be quite useful for the construction of the side chain of prostaglandin derivatives. (5) a new process of asymmetric cyclopropanation reaction successfully applied for the preparation of prostaglandin analogs.These synthetic methods are not only useful for the prostaglandin derivatives but also could be applied broadly in a wide variety of biologically active substances.