Quaedflieg Peter J L M, Kesteleyn Bart R R, Wigerinck Piet B T P, Goyvaerts Nicolaas M F, Vijn Robert Jan, Liebregts Constantinus S M, Kooistra Jaap H M H, Cusan Claudia
DSM Pharma Chemicals, LS-ASC&D, PO Box 18, 6160 MD Geleen, The Netherlands.
Org Lett. 2005 Dec 22;7(26):5917-20. doi: 10.1021/ol052554i.
[reaction: see text] 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.
[反应：见正文] 已开发出两条简短且高效的合成路线来制备双四氢呋喃醇2，它是研究中的HIV蛋白酶抑制剂TMC114（1）的关键结构单元。以S-2,3-O-异丙叉甘油醛（4）作为手性源，两条路线均基于硝基甲烷的非对映选择性迈克尔加成反应，主要生成顺式异构体6，随后进行涅夫氧化和环化反应以得到内酯缩醛8，再将其还原并环化得到2。
