Chiral Synthesis of Carbocyclic Analogues of l-ribofuranosides
Chiral Synthesis of Carbocyclic Analogues of l-ribofuranosides
复制标题
L-呋喃核苷碳环类似物的手性合成
DOI：
10.1021/jo9812330
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发表时间：
1999
影响因子：
3.6
通讯作者：
C. K. Chu
中科院分区：
文献类型：
--
作者：
Peiyuan Wang;L. Agrofoglio;Andrew Newton;C. K. Chu
天然产物 D-(-)-aristeromycin 和 neplanocin A 是具有生物学意义的碳环核苷的代表。天然和合成的碳环核苷 1, 2 对巨细胞病毒、4 疱疹病毒、5 乙型肝炎病毒、6 和人类免疫缺陷病毒 (HIV) 均表现出有趣的抗肿瘤3 和抗病毒活性。 7, 8 由于不存在真正的糖苷键，碳环核苷对核苷磷酸化酶 9 具有更高的代谢稳定性。其中，卡波韦7和6-环丙氨基嘌呤类似物1592U89（阿巴卡韦）10由于其有效的抗HIV活性而成为最受关注的化合物。 1592（阿巴卡韦）最近已获得 FDA 批准。最近，据报道一种新型碳环核苷BMS-200475具有有效的抗HBV活性，目前正在进行II期临床试验。 11 近年来，许多L-核苷，包括(-)-(2′R，5′S)-1-(2-羟甲基氧硫杂环戊烷-5-基)胞嘧啶(3TC)、12、13(-)--L-2′、3′-二脱氧-5-氟-3′-硫胞苷(FTC)、14-L-2′、 3'-二脱氧-5-氟胞苷 (L-FddC)、15、16 和-L-2'-氟-5-甲基阿拉伯呋喃糖基尿嘧啶 (L-FMAU) 17 显示出有希望的抗病毒活性。与 D-核苷相比，L-核苷 3TC 和 FTC 对 HIV 和乙型肝炎病毒 (HBV) 表现出更有效的抗病毒活性，并且毒性更低。 13, 18 因此，合成相应的 L-碳环核苷以期待有趣的抗病毒活性是很有意义的。我们之前报道过 L-环戊基碳环核苷的初步描述。 19 在本文中，我们报告了 L-环戊基碳环核糖核苷的实验细节、X 射线结构和确认。
Natural products, D-(-)-aristeromycin and neplanocin A, are representatives of biologically interesting carbocyclic nucleosides. Natural as well as synthetic carbocyclic nucleosides1, 2 have shown interesting antitumor3 and antiviral activities against cytomegalovirus, 4 herpes virus, 5 hepatitis B virus, 6 and human immunodeficiency virus (HIV). 7, 8 Carbocyclic nucleosides possess an increased metabolic stability against nucleoside phosphorylases9 because of the absence of a true glycosidic bond. Among them, carbovir7 and 6-cyclopropylaminopurine analogue, 1592U89 (Abacavir), 10 are the most interesting compounds due to their potent anti-HIV activities. 1592 (Abacavir) has recently been approved by the FDA. Recently, a novel carbocyclic nucleoside, BMS-200475, has been reported to exhibit potent anti-HBV activity, and it is currently undergoing phase II clinical trials. 11 In recent years, a number of L-nucleosides, including (-)-(2′ R, 5′ S)-1-(2-hydroxymethyloxathiolan-5-yl) cytosine (3TC), 12, 13 (-)--L-2′, 3′-dideoxy-5-fluoro-3′-thiacytidine (FTC), 14-L-2′, 3′-dideoxy-5-fluorocytidine (L-FddC), 15, 16 and-L-2′-fluoro-5-methylarabinofuranosyl uracil (L-FMAU) 17 have shown promising antiviral activity. Both L-nucleosides, 3TC and FTC, exhibit more potent antiviral activity against HIV and hepatitis B virus (HBV) and decreased toxicity in comparison to their D-counterparts. 13, 18 Therefore, it was of interest to synthesize the corresponding L-carbocyclic nucleosides in anticipation of interesting antiviral activity. We have previously reported a preliminary account of L-cyclopentyl carbocyclic nucleoside. 19 In this paper, we report the experimental details, X-ray structure, and confirmation of L-cyclopentyl carbocyclic ribonucleosides.