(+)-(2S,5R)-1-<2-<<(tert-butyldiphenylsilyl)oxy>methyl>-1,3-oxathiolan-5-yl>-cystosine | 145416-33-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: (+)-(2S,5R)-1-<2-<<(tert-butyldiphenylsilyl)oxy>methyl>-1,3-oxathiolan-5-yl>-cystosine
• 英文别名: (+)-(2S,5R)-1-(2-{[(tert-butyldiphenylsilyl)oxy]methyl}-1,3-oxathiolan-5-yl)-cystosine；4-amino-1-[(2S,5R)-2-[[tert-butyl(diphenyl)silyl]oxymethyl]-1,3-oxathiolan-5-yl]pyrimidin-2-one
• CAS: 145416-33-7
• 化学式: C₂₄H₂₉N₃O₃SSi
• 分子量: 467.664
• InChiKey: POSSOOZWEDVANZ-YADHBBJMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.99
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+)-(2S,5R)-1-<2-<<(tert-butyldiphenylsilyl)oxy>methyl>-1,3-oxathiolan-5-yl>-cystosine 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 以75%的产率得到ent-拉米夫定
  参考文献：
  名称：

  β-D-（2S，5R）-和α-D-（2S，5S）-1,3-氧杂硫杂环戊基核苷作为潜在抗HIV药物的结构活性关系。

  摘要：

  合成了具有天然核苷构型的β-D-（2S，5R）-和α-D-（2S，5S）-1,3-氧杂硫基丙基嘧啶和-嘌呤核苷，并针对人外周血单核（PBM）中的HIV-1进行了评估） 细胞。由D-甘露糖或D-半乳糖合成了用于合成各种核苷的关键中间体14。乙酸盐14与胸腺嘧啶，尿嘧啶，胞嘧啶和5-取代的尿嘧啶和胞嘧啶的缩合得到各种嘧啶核苷。乙酸酯14也与6-氯嘌呤和6-氯-2-氟嘌呤缩合，将其转化为各种嘌呤核苷。就胸腺嘧啶，尿嘧啶和5-取代的尿嘧啶衍生物而言，除5-氟尿嘧啶（α-异构体）衍生物55以外，大多数化合物均未表现出任何显着的抗HIV活性。在5-取代的胞嘧啶类似物中，发现5-溴胞嘧啶衍生物（β-异构体）68是最有效的抗HIV药物。在嘌呤衍生物的情况下，肌苷类似物（β-异构体）78被发现是6-取代嘌呤中最有效的抗HIV药物，而2-氨基-6-氯嘌呤衍生物（β-异构体）90显示最多。 2,6-二取代嘌呤系

  DOI：

  10.1021/jm00070a006
• 作为产物：
  描述：

  (tert-butyldiphenylsilanyloxy)acetaldehyde 在 四氯化锡 、 二异丁基氢化铝 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 生成 (+)-(2S,5R)-1-<2-<<(tert-butyldiphenylsilyl)oxy>methyl>-1,3-oxathiolan-5-yl>-cystosine
  参考文献：
  名称：

  Choi, Woo-Baeg; Wilson, Lawrence J.; Yeola, Suresh, Journal of the American Chemical Society, 1991, vol. 113, # 24, p. 9377 - 9379

  摘要：

  DOI：

文献信息

• An efficient synthesis of enantiomerically pure (+)-(2S,5R)-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine [(+)-BCH-189] from d-galactose
  作者：Lak S. Jeong、Antonio J. Alves、Sean W. Carrigan、Hea O. Kim、J. Warren Beach、Chung K. Chu

  DOI：10.1016/s0040-4039(00)92319-0

  日期：1992.1

  An efficient and short synthesis of enantiomerically pure (+)-BCH-189 has been accomplished from D-galactose via 1,6-thioanhydro-D-galactose.

  从D-半乳糖经1，6-硫代脱水-D-半乳糖完成了对映体纯的（+）-BCH-189的高效短合成。
• Inhibition of Human Immunodeficiency Virus Type 1 Replication by Phosphonoformate- and Phosphonoacetate-2',3'-Dideoxy-3'-thiacytidine Conjugates
  作者：Anne-Sophie Charvet、Michel Camplo、Philippe Faury、Jean-Christophe Graciet、Nicolas Mourier、Jean-Claude Chermann、Jean-Louis Kraus

  DOI：10.1021/jm00040a014

  日期：1994.7

  The synthesis of potential ''combined prodrugs'' where phosphonoformic acid (PFA) or phosphonoacetic acid (PAA) was attached to the 5'-O or N-4 position of 2',3'-dideoxy-3'-thiacytidine (BCH-189) is described. The anti-HIV-1 activity of 11 analogues which included carboxylic ester or phosphoric ester linkages of PFA or PAA to BCH-189 was determined in MT-4 cells. Of these compounds, the IC50 Of analogues 3, 4, 6, and 7 ranged from 0.2 to 100 mu M, while IC50 for BCH-189 in this system was 0.1 mu M. In vitro hydrolysis of the various esters or amides in human plasma indicated that these agents were relatively stable in the presence of plasma esterases with t(1/2) values of up to 120 min. Moreover, lipophilicity of these compounds (partition coefficient) was determined in order to establish correlation between lipophilicity and diffusion of BCH-189 analogues into the cells. The active compounds may exert their effects by extracellular or intracellular hydrolysis to the corresponding antiviral agent BCH-189, but intrinsic anti-HIV-1 activity of some of PAA and PFA adducts, themselves, may also be involved.
• Synthesis and anti-human immunodeficiency virus type 1 activities of new peptido-nucleoside analogues
  作者：M Camplo、V Niddam、P Barthélémy、P Faury、N Mourier、V Simon、AS Charvet、C Trabaud、JC Graciet、JC Chermann、JL Kraus

  DOI：10.1016/0223-5234(96)88298-5

  日期：1995.1

  In order to investigate whether antiproteasic peptides coupled to anti-reverse transcriptase nucleosides can act as inhibitors at the different stages of the HIV life cycle, various peptido-nucleosides were synthesized using methodologies involving (benzotriazol-1-yloxy)-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) as a coupling reagent between the N-4-cytosinyl moiety and the peptide carboxy terminus. The anti-HIV-1 activity in MT(4) cells of this new class of compounds and their anti-HIV protease activities were determined. Fourteen peptido-nucleosides have been synthesized and six act against both the HIV-protease and viral replication in vitro. Although the activity of the most potent compounds against HIV was found to be one order of magnitude lower than that of the parent nucleoside drug 2',3'-dideoxy-3'-thiacytidine, this new class of compound could be of biological interest. Indeed, since the in vitro half-lives (t(1/2)) of the hydrolysis of the most potent compounds in human plasma were found to be longer than 2.5 h, these analogues could reach the infected cells in their structural integrity. This observation does not exclude that these compounds may exert their antiviral effects as combined prodrugs through extracellular or intracellular hydrolysis.
• Synthesis and Biological Evaluation of a New N⁴-(N-Formyl Peptide)- 2′,3′-Dideoxy-3′-Thiacytidine as Anti-Hiv Prodrug
  作者：Michel Camplo、Philippe Faury、Anne-Sophie Charvet、Florence Lederer、Jean-Claude Chermann、Jean-Louis Kraus

  DOI：10.1080/07328319308019017

  日期：1993.7

  The synthesis of a new analogue of 2,3'-dideoxy-3'-thiacytidine 9 covalently linked to an N-formyl methionyl leucyl phenylalanine peptide is described. This new prodrug analogue has been tested on the one hand as activator of human polymorphonuclear leukocytes (an EC50 value of 1.8 10(-5) M was determined from dose-response curve for superoxide production) and on the other hand as inhibitor Of the syncitium formation caused by HIV-1 in MT4-cells (IC50 = 8.0 +/- 0.8 muM). In so far as this new prodrug possesses these two biological properties, it represents a useful ''chemical-head' capable of targeting specific receptors located on leukocytes membranes.
• Enantiomeric synthesis of (+)-BCH-189 [(+)-(2S,5R)-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine] from D-mannose and its anti-HIV activity
  作者：Chung K. Chu、J. Warren Beach、Lak S. Jeong、Bo G. Choi、Frank I. Comer、Antonio J. Alves、Raymond F. Schinazi

  DOI：10.1021/jo00023a010

  日期：1991.11