1-(5-O-acetyl-2,3-dideoxy-β-D-glycero-pent-2-enofuranosyl)-thymine | 77421-68-2

• 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: 1-(5-O-acetyl-2,3-dideoxy-β-D-glycero-pent-2-enofuranosyl)-thymine
• 英文别名: 1-(5-O-acetyl-2,3-dideoxy-β-D-glycero-pent-2-enofuranosyl)thymine；1-(5-O-Acetyl-2,3-dideoxy-β-D-glyceropent-2-enofuranosyl)thymine；5'-O-acetyl-2',3'-didehydro-2',3'-dideoxyuridine；5'-O-acetyl-2',3'-didehydro-3'-deoxythymidine；5'-acetyl D4T；5'-acetate-2',3'-diacetyl-5-methyluridine；Thymidine, 2',3'-didehydro-3'-deoxy-, 5'-acetate；[(2S,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methyl acetate
• CAS: 77421-68-2
• 化学式: C₁₂H₁₄N₂O₅
• 分子量: 266.254
• InChiKey: QIDSTUDQCSMSKL-VHSXEESVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(5-O-acetyl-2,3-dideoxy-β-D-glycero-pent-2-enofuranosyl)-thymine 在 ammonium hydroxide 作用下， 生成 司他夫定
  参考文献：
  名称：

  通过偶然的途径合成2'，3'-二脱氧-2'，3'-二氢核苷。

  摘要：

  本文描述了通过电化学反应“绿色”合成2'，3'-不饱和2'，3'-二脱氧核苷。使用这种方法，可以高收率合成d4T，d4U，ddA和ddI。

  DOI：

  10.1081/ncn-100002532
• 作为产物：
  描述：

  (2Xi)-3',5'-二-O-乙酰基-2'-溴-2'-脱氧-3,4-二氢胸苷 在 四乙基对甲苯磺酸铵 作用下， 以 甲醇 为溶剂， 反应 1.0h， 生成 1-(5-O-acetyl-2,3-dideoxy-β-D-glycero-pent-2-enofuranosyl)-thymine
  参考文献：
  名称：

  通过偶然的途径合成2'，3'-二脱氧-2'，3'-二氢核苷。

  摘要：

  本文描述了通过电化学反应“绿色”合成2'，3'-不饱和2'，3'-二脱氧核苷。使用这种方法，可以高收率合成d4T，d4U，ddA和ddI。

  DOI：

  10.1081/ncn-100002532

文献信息

• SYNTHESIS AND ANTI-HIV ACTIVITY OF [D4U]-[TROVIRDINE ANALOGUE] AND [D4T]-[TROVIRDINE ANALOGUE] HETERODIMERS AS INHIBITORS OF HIV-1 REVERSE TRANSCRIPTASE
  作者：D. Gavriliu、C. Fossey、A. Ciurea、Z. Delbederi、E. Sugeac、D. Ladurée、S. Schmidt、G. Laumond、A. M. Aubertin

  DOI：10.1081/ncn-120015066

  日期：2002.11

  A series of eleven heterodimers containing both a nucleoside analogue (d4U, d4T) and a non-nucleoside type inhibitor (Trovirdine analogue) were synthesized and evaluated for their ability to inhibit HIV replication. Unfortunately, the (N-3)d4U-Trovirdine conjugates (9a-e) and (N-3)d4T-Trovirdine conjugates (10a-f) were found to be inactive suggesting that the two individual inhibitor compounds do not

  合成了一系列同时含有核苷类似物（d4U，d4T）和非核苷类抑制剂（特洛维定类似物）的十一种异二聚体，并评估了它们抑制HIV复制的能力。不幸的是，发现（N-3）d4U-Trovirdine缀合物（9a-e）和（N-3）d4T-Trovirdine缀合物（10a-f）没有活性，这表明两种单独的抑制剂化合物在它们各自的抑制剂中不能同时结合各个站点。
• Process for preparing 5′-acetylstavudine
  申请人：Clariant Life Science Molecules (Italy) S.p.A.

  公开号：US06350873B2

  公开（公告）日：2002-02-26

  The present invention relates to a process for preparing 5′-acetylstavudine, an intermediate which is useful in the preparation of 2′,3′-didehydro-3′-deoxythymidine, an active principle with antiviral action which is commonly known as stavudine (D4T).

  这项发明涉及一种制备5'-乙酰司他夫定的过程，该中间体在制备2',3'-二去氢-3'-脱氧胸苷（一种常称为司他夫定（D4T）的具有抗病毒作用的活性成分）中有用。
• Synthesis of 5-Methyluridine and Its 5′-Mercapto-, 2-Amino-, and 4′,5′-Unsaturated Analogues
  作者：Vinko Škarié、Jasenka Matulié-Adamié

  DOI：10.1002/hlca.19800630808

  日期：1980.12.10

  Treatment of 2′,3′-O, O-isopropylidene-5-methyl-2,5′-anhydrouridine (8) with hydrogen sulfide or methanolic ammonia afforded 5′-deoxy-2′,3′-O, O-isopropylidene-5′-mercapto-5-methyluridine (9) and 2′,3′-O, O-isopropylidene-5-methyl-isocytidine (10), respectively. The action of ethanolic potassium hydroxide on 5′-deoxy-5′-iodo-2′,3′-O, O-isopropylidene-5-methyluridine (7) gave rise to the corresponding

  描述了四氧化将1-（2,3-二脱氧-β-D-甘油-戊-2-氨基呋喃糖基）胸腺嘧啶（1）立体定向顺式羟基化为1-β-D-呋喃呋喃糖基胸腺嘧啶（2）。用硫化氢或甲醇氨处理2'，3' - O，O-异亚丙基-5-甲基-2,5'-脱水尿苷（8）得到5'-deoxy-2'，3'- O，O-异亚丙基-5′-巯基-5-甲基尿苷（9）和2′，3′ - O，O-异亚丙基-5-甲基-异胞苷（10）。氢氧化钾乙醇溶液的上5'-脱氧-5'-碘- 2'，3'-动作Ô，O-异亚丙基-5-甲基尿苷（7）产生相应的1-（5-脱氧-β-D-促生长-4-烯呋喃糖基）5-甲基尿嘧啶（13）和2 - O-乙基-5-甲基尿苷（14 ）。
• Prodrugs of 2’,3’-Didehydro-3’-deoxythymidine
  作者：Tetsuya Hasegawa、Toshinobu Seki、Kazuhiko Juni、Mineo Saneyoshi、Takeo Kawaguchi

  DOI：10.1002/jps.2600821210

  日期：1993.12

  ester prodrugs of 2',3'-didehydro-3'-deoxythymidine (D4T) were synthesized, and their physicochemical properties were evaluated. Marked differences were observed. All of the prodrugs were chemically stable within the pH range 2-7. Hydrolysis of these esters was observed in all cases for four rat enzyme systems (plasma, liver, duodenum, and kidney), with D4T being regenerated. D4T or the prodrug was administered

  合成了6种2'，3'-didehydro-3'-脱氧胸苷（D4T）的酯前药，并对其理化性质进行了评估。观察到明显差异。所有前药在2-7的pH范围内化学稳定。在所有情况下，在四个大鼠酶系统（血浆，肝，十二指肠和肾脏）中都观察到了这些酯的水解，并再生了D4T。将D4T或前药口服给予大鼠，并测量D4T和相应的前药的血浆浓度。静脉内给药后D4T的半衰期为35.9分钟。由终期计算的半衰期和口服D4T后血浆中的最大浓度分别为35.9分钟和48.4 microM。口服前药（用水或橄榄油作为溶剂）后，
• Nasal Absorption of 2',3'-Didehydro-3'-deoxythymidine (D4T) and Its Esters in Rats.
  作者：Toshiyuki YAJIMA、Tetsuya HASEGAWA、Kazuhiko JUNI、Mineo SANEYOSHI、Takeo KAWAGUCHI

  DOI：10.1248/bpb.19.1234

  日期：——

  Nasal absorption of 2', 3'-didehydro-3'-deoxythymidine (D4T) and its esters (5'-acetyl D4T : C2-D4T and 5'-hemisuccinyl D4T : Suc-D4T) was investigated in rats. Bioavailability of D4T following intranasal (i.n.) administration was 98.0%, and the elimination from plasma was as rapid as that following intravenous administration of D4T. There seemed to be complete and rapid absorption of D4T from the nasal cavity. The plasma concentration-time profile of D4T following i.n. administration of C2-D4T was almost the same as that after administration of D4T itself. This suggests that C2-D4T was rapidly absorbed from the nasal cavity, and that some amount of dosing C2-D4T was hydrolyzed to D4T before entering the systemic circulation. In contrast, Suc-D4T showed slower absorption in the i.n. administration, and the plasma D4T level was maintained for a long period.

  研究了大鼠对 2'，3'-双脱氢-3'-脱氧胸苷（D4T）及其酯类（5'-乙酰基 D4T：C2-D4T 和 5'-hemisuccinyl D4T：Suc-D4T）的鼻腔吸收情况。鼻内给药后，D4T 的生物利用率为 98.0%，从血浆中消除的速度与静脉给药后一样快。鼻腔似乎可以完全、快速地吸收 D4T。静脉注射 C2-D4T 后，D4T 的血浆浓度-时间曲线与服用 D4T 本身后的血浆浓度-时间曲线几乎相同。这表明，C2-D4T 从鼻腔中被迅速吸收，在进入全身循环之前，一定剂量的 C2-D4T 被水解为 D4T。相比之下，Suc-D4T 在鼻腔给药时吸收较慢，血浆中的 D4T 水平维持了很长时间。