抗艾滋病先导化合物HMOA重要中间体的合成

Research and synthesis of a key intermediate of HMOA with anti-HIV activity

以2,5-二羟基-1,4-二噻烷为起始原料,经立体有择反应和利用保护试剂三氟甲基磺酸三甲基硅酯合成得到(2R,5R)-5-羟基-1,3-氧硫杂环戊烷-2-羧酸-(1R,2S,5R)-2-异丙基-5-甲基环己酯(Ⅰ)、(2R,5R)-5-乙酰氧基-1,3-氧硫杂环戊烷-2-羧酸-(1R,2S,5R)-2-异丙基-5-甲基环己酯(Ⅱ)和(2R,5S)-5-(6-氨基-嘌呤-9-基)-1,3-氧硫杂环戊烷-2-羧酸-(1R,2S,5R)-2-异丙基-5-甲基环己酯(Ⅲ).经过1H NMR和质谱及晶体结构分析等手段对其进行了结构表征.结果表明:化合物Ⅱ属于正交晶系,P212121空间群;晶胞参数a=0.533 0(1)nm,b=1.453 5(1)nm,c=2.354 7(1)nm,Z=4,V=1.824 2(4)nm3,Dc=1.174 g/cm3.最终可靠因子R1=0.072,wR2=0.063.分子中共有两个环,5个手性中心,六元环呈椅式构象,五元环呈信封式构象.

Starting from material 2,5-diol-1,4-dithiane, a new compound, （2R, 5 S）-5-（6-Amino-purine- 9-yl）-l, 3-oxathiolane-2-carboxylate-（1R, 2S, 5R）-2-isopro-pyl-5-methyl cyclohexyl ester, was ob- tained by using stereoselective synthesis and silylation reagent-trimethylsilyl trifluoromethanesulfona. The structure of this product was determined by 1H NMR, MS and single crystal X-ray diffraction analysis. The compound Ⅱ crystal belongs to orthorhombic system with space group P212121 and cell parameters a=0.533 0（1） nm,b=1.453 5（1） nm,c=2. 354 7（1） nm, Z=4, V=1. 824 2（4） nm3, Dc=1. 174 g/cm3 ,R1 =0. 072,wR2 =0. 063. The compound contains 2 rings and 5 ehiral centers.