Reese Colin B, Wu Qinpei
Department of Chemistry, King's College London, Strand, London, UK WC2R 2LS.
Org Biomol Chem. 2003 Sep 21;1(18):3160-72. doi: 10.1039/b306341k.
The synthesis of 2-amino-5-(2-deoxy-beta-D-ribofuranosyl)pyridine 2a, 2-amino-5-(2-deoxy-alpha-D-ribofuranosyl)-pyridine 23, 2-amino-5-(2-deoxy-beta-D-ribofuranosyl)-3-methylpyridine 2b, 2-amino-5-(2-deoxy-alpha-D-ribofuranosyl)-3-methylpyridine 29 and 5-(2-deoxy-beta-D-ribofuranosyl)-2,4-dioxopyrimidine [2'-deoxypseudouridine] 30a is described. These C-nucleosides are prepared either from 2-deoxy-3,5-O-(1,1,3,3-tetraisopropyldisiloxan-1,3-diyl)-D-ribofuranose 15 or from 2-deoxy-3,5-O-(1,1,3,3-tetraisopropyldisiloxan-1,3-diyl)-D-ribono-1,4-lactone 16, which are themselves prepared from 2-deoxy-D-ribose 13. The sugar derivatives are first allowed to react with the appropriate 5-lithio-pyridine or 5-lithio-pyrimidine derivatives, which are prepared from 5-bromo-2-(dibenzylamino)pyridine 12a, 5-bromo-2-[bis(4-methoxybenzyl)amino]pyridine 12b, 5-bromo-2-dibenzylamino-3-methylpyridine 25 and 5-bromo-2,4-bis(4-methoxybenzyloxy)pyrimidine 33. The products from the reactions between the lithio-derivatives and the lactol 15 are cyclized under Mitsunobu conditions; the products from the reactions between the lithio-derivatives and the lactone 16 are first reduced with L-Selectride before cyclization, also under Mitsunobu conditions. In all cases, the beta-anomers of the protected C-nucleosides are the predominant products. Finally, the separation of the alpha- and beta-anomers and the removal of all of the protecting groups are described.
描述了2-氨基-5-(2-脱氧-β-D-呋喃核糖基)吡啶2a、2-氨基-5-(2-脱氧-α-D-呋喃核糖基)吡啶23、2-氨基-5-(2-脱氧-β-D-呋喃核糖基)-3-甲基吡啶2b、2-氨基-5-(2-脱氧-α-D-呋喃核糖基)-3-甲基吡啶29和5-(2-脱氧-β-D-呋喃核糖基)-2,4-二氧代嘧啶[2'-脱氧假尿苷]30a的合成。这些C-核苷要么由2-脱氧-3,5-O-(1,1,3,3-四异丙基二硅氧烷-1,3-二基)-D-呋喃核糖15制备，要么由2-脱氧-3,5-O-(1,1,3,3-四异丙基二硅氧烷-1,3-二基)-D-核糖-1,4-内酯16制备，而它们本身是由2-脱氧-D-核糖13制备的。首先使糖衍生物与适当的5-锂代吡啶或5-锂代嘧啶衍生物反应，这些衍生物由5-溴-2-(二苄基氨基)吡啶12a、5-溴-2-[双(4-甲氧基苄基)氨基]吡啶12b、5-溴-2-二苄基氨基-3-甲基吡啶25和5-溴-2,4-双(4-甲氧基苄氧基)嘧啶33制备。锂代衍生物与内醇15之间反应的产物在Mitsunobu条件下环化；锂代衍生物与内酯16之间反应的产物在环化之前先用L-Selectride还原，同样是在Mitsunobu条件下。在所有情况下，受保护的C-核苷的β-异头物是主要产物。最后，描述了α-和β-异头物的分离以及所有保护基团的去除。
