Efficient synthetic method for biologically active compounds and their synthetic intermediates by new carbon-carbon bond formation reactions.

本项目致力于合成前列腺素和刺激素的短而高效的合成中间体的研究，这两个化合物都具有重要的生物活性，与包括癌症在内的老年人的疾病有关。用三丁基锡锂处理2-(苯基硒)-2-环戊烯(或环己烯)-1-酮，然后用烯丙基碘捕获它，得到烯丙基环烯酮。许多试剂，如四丁基氟化铵、碱、Lewis酸，或通过热处理和光处理，可以高产率地产生2-烯丙基-2-环烷基-1-酮。根据该方案，从手性4-硅氧基-2-环戊烯-1-酮可以直接高产率地合成前列腺素及其类似物的关键中间体。该方法包括迄今已知的最短和最方便的过程。在上述步骤中，苯硫基和三烷基硅基可以分别取代苯基亚硒基和三丁基锡基。2-(苯基亚硒基)-2-环戊烯-1-酮、三丁基锡基锂和醛的三组分偶联反应高产率地制备了2-(1-羟基烷基)-2-环戊烯-1-酮，为高效合成刺激素及其类似物开辟了一条新途径。

This project deals with the study on the short and efficient synthesis of the synthetic intermediates of prostaglandins and punaglandins, both of which are known to have important biological activities related to the deseases of old people including cancer.Treatment of 2-(phenylseleno)-2-cyclopenten(or cyclohexen)-1-one with tributylstannyllithium gave the enolate witch was then trapped with allyl iodide to afford the allylated cycloalkenone. Destannylselenenylation could be effected by numerous reagents such as tetrabutylammonium fluoride, bases, Lewis acids, or by thermal and photo treatments, giving 2-allyl-2-cylcoalken-1-one in high yields. According to this protocol, the key intermediate for prostaglandins and their analogs could be prepared in high yield directly from chiral 4-siloxy-2-cyclopenten-1-one. The method comprises the shortest and the most convenient process ever known. In the above procedure the phenylthio and trialkylsilyl groups were shown to be able to be substituted for the phenylseleno and the tributylstannyl groups, respectively.The three-component coupling of 2-(phenylseleno)-2-cyclopenten-1-one, tributylstannyllithium, and aldehydes led to a high yield preparation of 2-(1-hydroxyalkyl)-2-cyclopenten-1-ones, which opened a way to the efficient synthesis of punaglandins and their analogs.