Jeong L S, Lim B B, Marquez V E
Laboratory of Medicinal Chemistry, National Cancer Institute, NIH, Bethesda, MD 20892.
Carbohydr Res. 1994 Sep 1;262(1):103-14. doi: 10.1016/0008-6215(94)84007-5.
A new sugar, methyl 5-O-benzoyl-2,3-dideoxy-2,3-difluoro-D-lyxofuranoside (8), which features fluorine substituents on adjacent carbon positions above the plane of the tetrahydrofuran ring, was synthesized from 1,2: 5,6-di-O-isopropylidine-alpha-D-allofuranose in seven steps and 22% overall yield. During the synthesis, introduction of the second fluorine atom required conditions more forceful than those normally used with diethylaminosulfur trifluoride (DAST). An attempt to use 8 in the synthesis of the all-cis nucleoside, 1-(2,3-dideoxy-2,3-difluoro-beta-D-lyxofuranosyl)thymine, failed to give the desired product, providing instead 1-(3-deoxy-3-fluoro-2-O-methyl-beta-D-xylofuranosyl)thymine (11), the structure of which was confirmed by an independent synthesis. Formation of the rearranged product occurred with the concurrent loss of fluorine and retention of the methoxy group which was transposed from the anomeric to the 2'-position. The present work highlights the reactive nature of this novel dideoxydifluoro sugar precursor.
一种新的糖，5-O-苯甲酰基-2,3-二脱氧-2,3-二氟-D-来苏呋喃糖苷（8），其在四氢呋喃环平面上方的相邻碳位置上具有氟取代基，由1,2:5,6-二-O-异亚丙基-α-D-阿洛呋喃糖经七步合成，总产率为22%。在合成过程中，引入第二个氟原子所需的条件比通常用于三氟甲磺酸二乙胺（DAST）的条件更为苛刻。尝试使用8合成全顺式核苷1-(2,3-二脱氧-2,3-二氟-β-D-来苏呋喃糖基)胸腺嘧啶，但未能得到所需产物，而是得到了1-(3-脱氧-3-氟-2-O-甲基-β-D-木呋喃糖基)胸腺嘧啶（11），其结构通过独立合成得到证实。重排产物的形成伴随着氟的同时损失和甲氧基的保留，甲氧基从异头位置转移到2'-位置。本工作突出了这种新型二脱氧二氟糖前体的反应活性。
