22 海洋産多環状エーテル天然物の合成研究(口頭発表の部)

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Recently, marine polycyclic ethers as exemplified by brevetoxin B (1), hemibrevetoxin B (2), and maitotoxin (3) have attracted the attention of synthetic organic chemists due to their unusual structural framework, novel functionalities, and potent biological activities. We now report an efficient method for the synthesis of 6- and 7-membered ethers and its application to the synthesis of the C-, CD-, and ABC-ring systems of 2 and the S-, Y-, and ST-ring systems of 3. 1. Synthesis of 6- and 7-membered ethers A novel rearrangement used in the total synthesis of lasalocid A was further investigated using 5- and 6-membered ethers, 6 and 7, having the mesylate group on the side chain. Upon treatment with Zn(OAc)_2 in aq AcOH at reflux, the rearrangement took place with complete stereoselection giving the ring-expanded ethers, 8 and 9, in good yield. 2. Synthetic study of hemibrevetoxin B (2) 2-1. Synthesis of C- and CD-ring systems The present rearrangement was successfully applied to the synthesis of the C- and CD-ring systems of 2. The Sharpless asymmetric epoxidation (AE) of 16 gave α-epoxide 17, which was treated with PhCOOH and Ti(OiPr)_4 followed by Dowex to give 18. The alcohol 18 was subjected to the Sharpless AE and cyclization with PPTS to give 20, which was converted into mesylates 23 and 24. The treatment of 23 and 24 with Zn(OAc)_2 produced the ring-expanded ethers 25 and 26 corresponding to the C-ring system, respectively. The synthesis of the 7, 7-membered ether 30 corresponding to the CD-ring system was also accomplished by the double rearrangement of the 6,6-membered ether 29 prepared from 22 via 27. 2-2. Synthesis of ABC-ring system The synthesis of the ABC-ring system of 2 was investigated using the model compound 11. 6-Endo cyclization of vinyl epoxide 34 prepared from 11 was examined using Nicolaou's procedure but the results were unsatisfactory giving a mixture of 6- and 5-membered ethers, 35 and 36. After several attempts, the 6-endo cyclization was found to be accomplished using styryl epoxide 37. Desilylation of 37 with n-Bu_4NF followed by PPTS treatment gave the desired 6-membered ether 38 with complete stereoselection. Reaction of 39 with allylMgCl-ZnCl_2 produced 40a and 40b in a ratio of 1.7:1. Ozonolysis of 40a followed by treatment with CH_2=C(CH_2OAc)CH_2TMS in the presence of TMSOTf gave 42. α-Alcohol 43 prepared from 40b was also converted into β-alcohol 42 by Jones oxidation followed by L-Selectride reduction. The alkaline hydrolysis of 42 followed by MnO_2 oxidation gave the α, β-unsaturated aldehyde 46 corresponding to the ABC-ring system of 2. The total synthesis of 2 is now in progress in this laboratory. 3. Synthesis of S-. Y- and ST-ring systems of maitotoxin (3) The present rearrangement was also successfully applied to the synthesis of the S-, Y-, and ST-ring systems of maitotoxin (3).
天然有機化合物討論会の論文
1995-09-01

22 海洋産多環状エーテル天然物の合成研究(口頭発表の部)

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