Development of Novel Tandem Cyclization Using Palladium Catalyst and Its Application to the Synthesis of Natsural Products

多取代的γ-内酯结构可以在许多天然产物中发现，特别是产生聚酮大环内酯的微生物。γ-内酯结构的立体选择性合成是一个非常重要的合成方法，我们最近发展了一种以钯（II）为催化剂，通过半缩醛中间体的环化反应，发现了三取代四氢吡喃的立体选择性结构，结合钯（II）催化的杂环化反应，我们将该方法应用于具有γ-内酯结构的天然产物的合成。含仲醇的醛在乙醇存在下，用PdCl_2（Ph_3CN）_2在THF中进行环化反应，立体选择性地得到环化产物。另一方面，螺酮缩酮是多环醚和聚丙酸酯的重要组成部分。这些螺缩酮化合物表现出有趣的生理活性。本文以1，11-二羟基-7-氧代-5-苯基-2-十一碳烯为原料，在四氢呋喃（THF）溶液中，用10mol%PdCl_2（Ph_3CN）_2进行分子内环化反应，得到了一个立体异构体的螺酮缩酮化合物，并对该化合物的结构进行了表征。我们尝试合成螺菌素A和B，它们是从甜菊紫素Tu 4113中分离的新型聚酮型抗生素。以PdCl_2（Ph_3CN）_2为催化剂，成功地实现了底物（二羟基酮化合物）的关键串联环化，得到了螺菌素A的重要中间体螺缩酮化合物

The polysubstituted γ-lactone structure can be found in many natural products, particularly polyketide macrolide producing microorganisms. It is a very important to develop synthetic methodology for the streo-selective construction of the γ-lactone structure.We recently developed a cyclization via a hemiacetal intermediate using palladium (II) cartalyst and found a stereo selective construction of trisubstituted tetrahydropyran.In connection with the palladium (II) catalyzed hetero-cyclization, we applied the method to synthesis of a natural product having a γ-lactone structure. The cyclization of the aldehyde containing the secondary alcohol using PdCl_2(Ph_3CN)_2 in THF in the presence of alcohol gave the cyclized product, stereo-selectively. 5-Epi-prelactone C was also synthesized by the similar method.On the other hand, the spiroketal moiety is one of the most important constituents of polycyclic ethers and polypropionates. These spiroketal compounds exhibit interesting physiological activities. Therefore stereo-selective construction of the spiroketal structure is very important in organic synthesis.Then, we studied the construction of spiroketal structure by intramolecular tantem cyclization using palladium (II) cartalyst.Treatment of 1,11-dihydroxy-7-oxo-5-phenyl-2-undecene with 10 mol% PdCl_2(Ph_3CN)_2 in THF afforded the spiroketal compound as a single stereo-isomer.Next, we tried the synthesis of spirofungin A and B, novel polyketide-type antibiotics isolated from Steptomyces violaceusiger Tu 4113. The key tandem cyclization of the substrate (the dihydroxyketone compound) was achieved successfully by treatment with PdCl_2(Ph_3CN)_2 to give a spiroketal compound, which was the important intermediate for the synthesis of spirofungin A