1,3-dideoxy-3-<(phenylmethoxy)methyl>-5-O-(phenylmethyl)-D-ribofuranose 2-(4-methylbenzenesulfonate) | 132523-63-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1,3-dideoxy-3-<(phenylmethoxy)methyl>-5-O-(phenylmethyl)-D-ribofuranose 2-(4-methylbenzenesulfonate)
• 英文别名: 1,4-anhydro-5-O-benzyl-3-C-benzyloxymethyl-3-deoxy-2-O-p-toluenesulfonyl-D-ribitol；1,3-Dideoxy-3-[(phenylmethoxy)methyl]-5-O-(phenylmethyl)-D-ribofuranose, 2-(4-methylbenzenesulfonate)；1,3-dideoxy-3-[(phenylmethoxy)methyl]-5-O-(phenylmethyl)-D-ribofuranose 2-(4-methylbenzenesulfonate)；[(3R,4R,5S)-4,5-bis(phenylmethoxymethyl)oxolan-3-yl] 4-methylbenzenesulfonate
• CAS: 132523-63-8
• 化学式: C₂₇H₃₀O₆S
• 分子量: 482.598
• InChiKey: FDBWFYABCUJASM-PFBJBMPXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  34
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  79.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1,3-dideoxy-3-<(phenylmethoxy)methyl>-5-O-(phenylmethyl)-D-ribofuranose 2-(4-methylbenzenesulfonate) 在 palladium on activated charcoal 吡啶 、 ammonium hydroxide 、 18-冠醚-6 、 potassium carbonate 、 环己烯 、 4-氯苯基二氯磷酸酯 作用下， 以 1,4-二氧六环 、 乙醇 、 二甲基亚砜 为溶剂， 反应 199.5h， 生成 <3S-(3α,4β,5α)>-4-amino-1--2(1H)-pyrimidinone
  参考文献：
  名称：

  Synthesis and antiviral activity of novel isonucleoside analogs

  摘要：

  A series of branched-chain sugar isonucleosides was synthesized and evaluated for antiviral activity against herpesviruses. The preparation of homochiral [3S-(3alpha,4beta,5alpha)]-2-amino-1,9-dihydro-9-[tetrahydro-4,5-bis(hydroxymethyl)-3-furanyl]-6H-purin-6-one (7, BMS-181,164) and related compounds was stereospecifically achieved starting from 1,2-isopropylidene-D-xylofuranose (10). An efficient two-step reduction of the anomeric center of bis-acetate 18 involved formation of the chloride intermediate 19, followed by diisobutylaluminum hydride reduction. Tosylation of the resulting alcohol 20 provided the key intermediate 21, which was coupled with a variety of nucleobase anions. Several members of this new class of compounds possess activity against herpes simplex virus types 1 and 2 (HSV-1 and -2), varicella-zoster virus (VZV), and human cytomegalovirus (HCMV). Compound 7 exhibits potent and selective activity against thymidine kinase encoding herpesviruses, in particular, HSV-1 and HSV-2. Evaluation of compound 7 for inhibition of WI-38 cell growth indicated an ID50 of > 700 muM. Although the antiherpetic activity in vitro of 7 is less than that of acyclovir (1), compound 7 displays superior efficacy in mouse model infections. The (bromovinyl)uridine analog 8 (BMS-181,165) also exhibits selective activity against HSV-1 and VZV, with no cytostatic effect on WI-38 cell growth at > 800 muM. Compound 8 is active against simian varicella virus and is efficacious in the corresponding monkey model.

  DOI：

  10.1021/jm00061a013
• 作为产物：
  描述：

  3-deoxy-1,2-O-(1-methylethylidene)-3-<(phenylmethoxy)methyl>-5-O-(phenylmethyl)-α-D-ribofuranose 在 盐酸 、 4-二甲氨基吡啶 、 ammonium sulfate 、 六甲基二硅氮烷 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 23.0h， 生成 1,3-dideoxy-3-<(phenylmethoxy)methyl>-5-O-(phenylmethyl)-D-ribofuranose 2-(4-methylbenzenesulfonate)
  参考文献：
  名称：

  1,2,4-三唑-3-甲酰胺新型异核苷的合成及生物学评价

  摘要：

  摘要 分别以 D-核糖和 D-木糖为原料，高效合成了新型 1,2,4-三唑异核苷（1 和 2）。关键步骤分别是环硫酸盐 8 与 1,2,4-三唑-3-羧酸甲酯的缩合和甲苯磺酸酯 15 与 1,2,4-三唑-3-羧酸甲酯的亲核置换。

  DOI：

  10.1080/00397910500213864

文献信息

• Purinyl tetrahydrofurans
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US05059690A1

  公开（公告）日：1991-10-22

  Antiviral activity is exhibited by compounds having the formula ##STR1## and pharmaceutically acceptable salts thereof wherein R.sub.1 is a purine or pyrimidine base or an analog thereof and R.sub.2 and R.sub.3 are independently hydrogen, --PO.sub.3 H.sub.2 or ##STR2## wherein X.sub.7 is hydrogen, alkyl, substituted alkyl or aryl.

  化合物具有以下结构式的抗病毒活性：##STR1##及其药学上可接受的盐，其中R.sub.1是嘌呤或嘧啶碱基或其类似物，R.sub.2和R.sub.3分别是氢、--PO.sub.3 H.sub.2或##STR2##其中X.sub.7是氢、烷基、取代烷基或芳基。
• Synthesis and Biological Evaluation of Novel Isonucleosides with 1,2,4‐Triazole‐3‐Carboxamide
  作者：Myong Jung Kim、Soon Yong Chung、Moon Woo Chun

  DOI：10.1080/00397910500213864

  日期：2005.10.1

  Novel 1,2,4‐triazole isonucleosides (1 and 2) were efficiently synthesized starting from D‐ribose and D‐xylose, respectively. The key steps were condensation of cyclic sulfate 8 with methyl‐1,2,4‐triazole‐3‐carboxylate and nucleophilic displacement of the tosylate 15 with methyl‐1,2,4‐triazole‐3‐carboxylate, respectively.

  摘要 分别以 D-核糖和 D-木糖为原料，高效合成了新型 1,2,4-三唑异核苷（1 和 2）。关键步骤分别是环硫酸盐 8 与 1,2,4-三唑-3-羧酸甲酯的缩合和甲苯磺酸酯 15 与 1,2,4-三唑-3-羧酸甲酯的亲核置换。
• Synthesis and antiviral activity of novel isonucleoside analogs
  作者：Joseph A. Tino、Junius M. Clark、A. Kirk Field、Glenn A. Jacobs、Karen A. Lis、Teresa L. Michalik、Bridgette McGeever-Rubin、William A. Slusarchyk、Steven H. Spergel

  DOI：10.1021/jm00061a013

  日期：1993.4

  A series of branched-chain sugar isonucleosides was synthesized and evaluated for antiviral activity against herpesviruses. The preparation of homochiral [3S-(3alpha,4beta,5alpha)]-2-amino-1,9-dihydro-9-[tetrahydro-4,5-bis(hydroxymethyl)-3-furanyl]-6H-purin-6-one (7, BMS-181,164) and related compounds was stereospecifically achieved starting from 1,2-isopropylidene-D-xylofuranose (10). An efficient two-step reduction of the anomeric center of bis-acetate 18 involved formation of the chloride intermediate 19, followed by diisobutylaluminum hydride reduction. Tosylation of the resulting alcohol 20 provided the key intermediate 21, which was coupled with a variety of nucleobase anions. Several members of this new class of compounds possess activity against herpes simplex virus types 1 and 2 (HSV-1 and -2), varicella-zoster virus (VZV), and human cytomegalovirus (HCMV). Compound 7 exhibits potent and selective activity against thymidine kinase encoding herpesviruses, in particular, HSV-1 and HSV-2. Evaluation of compound 7 for inhibition of WI-38 cell growth indicated an ID50 of > 700 muM. Although the antiherpetic activity in vitro of 7 is less than that of acyclovir (1), compound 7 displays superior efficacy in mouse model infections. The (bromovinyl)uridine analog 8 (BMS-181,165) also exhibits selective activity against HSV-1 and VZV, with no cytostatic effect on WI-38 cell growth at > 800 muM. Compound 8 is active against simian varicella virus and is efficacious in the corresponding monkey model.