Stereoselective and efficient synthesis of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol
Stereoselective and efficient synthesis of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol
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DOI：
10.1021/ol052554i
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发表时间：
2005-12-22
期刊：
影响因子：
5.2
通讯作者：
Cusan, C
中科院分区：
文献类型：
--
作者：
Quaedflieg, PJLM;Kesteleyn, BRR;Cusan, C
[图表]双-THF-醇 2 是研究中的 HIV 蛋白酶抑制剂 TMC114 的关键组成部分，现已开发出两条短而高效的合成路线 (1)。使用 S-2,3-O-异亚丙基甘油醛 (4) 作为手性来源，两条路线均基于硝基甲烷的非对映选择性迈克尔加成，主要得到顺式同系物 6，然后进行 Nef 氧化和环化，得到内酯缩醛 8，将其还原并环化，得到 2。
[GRAPHICS]Two short and efficient synthesis routes have been developed for bis-THF-alcohol 2, a key building block of the investigational HIV protease inhibitor TMC114 (1). Using S-2,3-O-isopropylideneglyceraldehyde (4) as the source of chirality, both routes are based on a diastereoselective Michael addition of nitromethane to give predominantly the syn congeners 6 followed by a Nef oxidation and cyclization to afford lactone acetals 8, which are reduced and cyclized to give 2.