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

多取代γ-内酯结构广泛存在于许多天然产物中，尤其是聚酮大环内酯产生菌。γ-内酯结构的合成方法学是非常重要的。我们最近在钯(II)催化下，通过半缩醛中间体进行了环化反应，发现了三取代四氢吡喃的立体选择性结构。针对钯(II)催化的杂环化反应，我们将该方法应用于合成具有γ-内酯结构的天然产物。在乙醇存在下，含仲醇的醛在四氢呋喃中用PdCl2(Ph3CN)2进行环化反应，得到立体选择性的环化产物。另外，螺酮是多环醚和聚丙酸酯中最重要的成分之一。这些螺酮类化合物显示出有趣的生理活性。因此，螺酮结构的立体选择性构筑在有机合成中是非常重要的。然后，我们研究了以钯(II)为催化剂的分子内环合构筑螺酮结构的方法。1，11-二羟基-7-氧代-5-苯基-2-十一烯在四氢呋喃中与10mol%的PdCl2(Ph_3CN)_2反应得到了螺酮类化合物。其次，我们尝试了从紫链霉菌Tu 4113中分离得到新型聚酮类抗生素螺菌素A和B。在PdCl2(Ph_3CN)_2的作用下，底物(二羟基酮类化合物)成功地实现了关键的串联环化反应，得到了螺酮类化合物，这是合成螺菌素A的重要中间体

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