PREPARATION OF 1-(2,3-DIDEOXY-BETA-D-GLYCERO-PENT-2-ENOFURANOSYL)THYMINE (D4T)1 AND 2',3'-DIDEOXYADENOSINE (DDA) - GENERAL-METHODS FOR THE SYNTHESIS OF 2',3'-OLEFINIC AND 2',3'-DIDEOXY NUCLEOSIDE ANALOGS ACTIVE AGAINST HIV
PREPARATION OF 1-(2,3-DIDEOXY-BETA-D-GLYCERO-PENT-2-ENOFURANOSYL)THYMINE (D4T)1 AND 2',3'-DIDEOXYADENOSINE (DDA) - GENERAL-METHODS FOR THE SYNTHESIS OF 2',3'-OLEFINIC AND 2',3'-DIDEOXY NUCLEOSIDE ANALOGS ACTIVE AGAINST HIV
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DOI：
10.1021/jo00281a017
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发表时间：
1989-09-29
影响因子：
3.6
通讯作者：
MARTIN, JC
中科院分区：
文献类型：
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作者：
MANSURI, MM;STARRETT, JE;MARTIN, JC
2“，3”-不饱和胸苷和胞苷类似物2和3、2“，3”-双脱氧胞苷（4）和2“，3”-双脱氧腺苷（5）已显示出体外抗HIV的活性;因此，制备这些物质的方法是令人感兴趣的。将核糖核苷的邻位二醇官能团转化为2“，3”-烯属2“，3”-双脱氧类似物代表了制备这些不饱和核苷类似物的最通用途径之一。在这里，我们报告三种方法将核糖核苷转化为相应的烯烃。使用的方法是Corey-Winter反应，包括环状硫代碳酸酯的断裂10，由2“，3”-O-烷氧基亚甲基环状原酸酯形成烯烃15，和2“，3”卤代乙酸酯的还原消除20、23、26、27和30。在这三种方法中，发现最后一种方法是最通用的，因为中间体顺式-2“-溴-3”-O-乙酰基-2“-脱氧核糖基嘧啶20、23和30或反式-3”-（2“）-溴-2”（3“-O-乙酰基-3”（2“）-脱氧阿拉伯糖基嘌呤26和27容易转化为相应的烯烃。作为制备饱和2“，3”-双脱氧类似物的一个实例，通过催化还原相应的烯属核苷29获得2“，3”-双脱氧腺苷（5）。
The 2'',3''-unsaturated thymidine and cytidine analogues 2 and 3, respectively, 2'',3''-dideoxycytidine (4), and 2'',3''-dideoxyadenosine (5) have been shown to be active in vitro against HIV; therefore, methods for the preparation of these substances are of interest. The conversion of the vicinal diol functionality of ribonucleosides to the 2'',3''-olefinic 2'',3''-dideoxy analogues represents one of the most general routes for the preparation of these unsaturated nucleoside analogues. Here, we report on three methods for transforming ribonucleosides to the corresponding olefins. The methods used were the Corey-Winter reaction involving the fragmentation of a cyclic thionocarbonate 10, olefin formation from 2'',3''-O-alkoxymethylidene cyclic ortho esters 15, and the reductive elimination of the 2'',3'' halo acetates 20, 23, 26, 27, and 30. Of these three, the last method was found to be the most versatile, since the intermediate cis-2''-bromo-3''-O-acetyl-2''-deoxyribosylpyrimidines 20, 23, and 30 or the trans-3''-(2'')-bromo-2''(3)''-O-acetyl-3''(2'')-deoxyarabinosylpurines 26 and 27 are readily transformed to the corresponding olefins. As an example of the preparation of a saturated 2'',3''-dideoxy analogue, 2'',3''-dideoxyadenosine (5) was obtained by catalytic reduction of the corresponding olefinic nucleoside 29.