Stereoselective photochemical 1,3-dioxolane addition to 5-alkoxymethyl-2(5H)-furanone:: Synthesis of bis-tetrahydrofuranyl ligand for HIV protease inhibitor UEC-94017 (TMC-114)
Stereoselective photochemical 1,3-dioxolane addition to 5-alkoxymethyl-2(5H)-furanone:: Synthesis of bis-tetrahydrofuranyl ligand for HIV protease inhibitor UEC-94017 (TMC-114)
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DOI：
10.1021/jo049156y
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发表时间：
2004-11-12
影响因子：
3.6
通讯作者：
Noetzel, M
中科院分区：
文献类型：
--
作者：
Ghosh, AK;Leshchenko, S;Noetzel, M
报道了一种简便的(3R，3aS，6aR)-3-hydroxyhexahydrofuro[2，3-b]furan，的合成方法，该配体是HIV蛋白水解酶抑制剂UIC-94017的高亲和力非肽配体。这种抑制剂正在进行高级临床试验。以新型立体选择性光化学方法1，3-二氧杂环戊烷与5(S)-苄氧甲基-2(5H)-呋喃酮的加成反应为关键步骤。通过固定化脂肪酶催化的(+/-)-1-(苄氧基)-3-丁烯-2-醇的选择性酰化反应和GRubbs催化的闭环烯烃歧化反应，制备了高对映体过量的呋喃酮衍生物。光学活性的双四氢呋喃被转化为蛋白酶抑制剂2(UIC-94017)。
A convenient synthesis of (3R,3aS,6aR)-3-hydroxyhexahydrofuro[2,3-b]furan, a high-affinity nonpeptidal ligand for HIV protease inhibitor UIC-94017, is described. This inhibitor is undergoing advanced clinical trials. The synthesis utilizes a novel stereoselective photochemical 1,3-dioxolane addition to 5(S)-benzyloxymethyl-2(5H)-furanone as the key step. The requisite furanone derivative was prepared in high enantiomeric excess by an immobilized lipase-catalyzed selective acylation of (+/-)-1-(benzyloxy)-3-buten-2-ol and a ring-closing olefin metathesis with Grubbs' catalyst. Optically active bis-THF was converted to protease inhibitor 2 (UIC-94017).