Wittig rearrangement of furylmethyl ethers and application to natural product synthesis

通过2-糠基甲基醚的Wittig重排进行了手性转移。（2S,3Z）和(2S,3E)-3-戊烯-2-基醚经过完全手性转移重排，分别得到（1R,2S,3E）和(1R,2R,3E)-1-（2-呋喃基）-2-甲基-3-戊烯-1-醇。甾体侧链的立体选择性构建，如脱皮激素、异丙醇内酯和油菜素内酯，已经完成了采用16-糠氧基类固醇的Wittig重排作为关键步骤。（17E）-16α和(17Z)-16β-糠氧基-6β-甲氧基-3α， 5-环-5α-孕-17-烯进行立体选择性重排，分别得到（20S,22S,23Z,25Z）和(20S,22S,23Z,25Z)-23,26-环氧-22-羟基-6β-甲氧基-3α， 5-环-27- 5α-cholesta-16,23,25-三烯。具有20S和22S立体化学的甾体可转化为脱皮酮和异戊内酯侧链，而(20S,22R)-异构体可转化为油菜素内酯侧链。利用环糠基醚的分子内Wittig重排，对假紫菀内酯核的合成进行了研究。主要特点是(5E)-5-甲基-3,16-二氧杂环[11.2.1]十六烷基-1(15),5,13-三烯的非对映选择性Wittig重排，使(2R^*,3R^*)-3-异丙基-13-二氧杂环[8.2.1]三氧杂环-1(12)，10-二烯-2-醇在靶分子的C1和C2位置具有正确的立体化学结构。

Chirality transfer via the Wittig rearrangement of 2-furylmethyl ethers has been carried out. Both (2S,3Z)-and (2S,3E)-3-penten-2-yl ethers rearranged with complete chirality transfer to give (1R,2S,3E)-and (1R,2R,3E)-1-(2-furyl)-2-methyl-3-penten-1-ols, respectively.Stereoselective construction of steroidal side chains, such as ecdysone, withanolide, and brassinolide, has been accomplished employing the Wittig rearrangement of 16-furfuryloxy steroids as a key step. Wittig rearrangement of (17E)-16α-and (17Z)-16β-furfuryloxy-6β-methoxy-3α, 5-cyclo-5α-pregn-17-enes proceeded stereoselectively to afford (20S,22S,23Z,25Z)-and (20S,22S,23Z,25Z)-23,26-epoxy-22-hydroxy-6β-methoxy-3α, 5-cyclo-27-nor-5α-cholesta-16,23,25-trienes, respectively. Steroid possessing 20S and 22S stereochemistries could be transformed into ecdysone and withanolide side chains, whereas (20S,22R)-isomer would lead to brassinolide side chain.Studies toward the synthesis of the core of pseudopterolide have been carried out by the utilization of the intramolecular Wittig rearrangement of cyclic furfuryl ether. The key feature is the diastereoselective Wittig rearrangement of (5E)-5-methyl-3,16-dioxabicyclo [11.2.1] hexadeca-1(15), 5,13-triene providing (2R^*,3R^*)-3-isopropyl-13-oxabicyclo [8.2.1] trideca-1(12), 10-dien-2-ol with the correct stereochemistries at the C1 and C2 positions of the target molecule.