(S)-2-Fluorosuccinic anhydride | 135119-66-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-2-Fluorosuccinic anhydride
• 英文别名: (3S)-3-fluorooxolane-2,5-dione
• CAS: 135119-66-3
• 化学式: C₄H₃FO₃
• 分子量: 118.064
• InChiKey: HSXMRBZVQXUROA-REOHCLBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  8
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  L-薄荷醇 、 (S)-2-Fluorosuccinic anhydride 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 生成 (S)-2-Fluoro-succinic acid 1-((1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl) ester
  参考文献：
  名称：

  5-卟啉生物合成的潜在抑制剂5-氨基乙酰戊酸的氟化类似物的合成

  摘要：

  通过修饰涉及γ-内酯中间体的5-氨基戊酸（ALA）的新路线，可以高收率合成5-氨基-2-氟戊酸3。初步研究表明3是ALA脱水酶的抑制剂，ALA脱水酶是四吡咯生物合成的早期酶。

  DOI：

  10.1016/s0022-1139(00)80192-x
• 作为产物：
  描述：

  (S)-2-氟丁二酸 在 三氟乙酸酐 作用下， 反应 3.0h， 以86%的产率得到(S)-2-Fluorosuccinic anhydride
  参考文献：
  名称：

  5-卟啉生物合成的潜在抑制剂5-氨基乙酰戊酸的氟化类似物的合成

  摘要：

  通过修饰涉及γ-内酯中间体的5-氨基戊酸（ALA）的新路线，可以高收率合成5-氨基-2-氟戊酸3。初步研究表明3是ALA脱水酶的抑制剂，ALA脱水酶是四吡咯生物合成的早期酶。

  DOI：

  10.1016/s0022-1139(00)80192-x

文献信息

• Neuromuscular Blocking Activity and Therapeutic Potential of Mixed-Tetrahydroisoquinolinium Halofumarates and Halosuccinates in Rhesus Monkeys
  作者：Eric E. Boros、Vicente Samano、John A. Ray、James B. Thompson、David K. Jung、Istvan Kaldor、Cecilia S. Koble、Michael T. Martin、Virgil L. Styles、Robert A. Mook、Paul L. Feldman、John J. Savarese、Matthew R. Belmont、Eric C. Bigham、G. Evan Boswell、Mir A. Hashim、Sanjay S. Patel、James C. Wisowaty、Gary D. Bowers、Caroline L. Moseley、John S. Walsh、Mindy J. Reese、Randy D. Rutkowske、Andrea M. Sefler、Timothy D. Spitzer

  DOI：10.1021/jm020574+

  日期：2003.6.1

  Structure-activity relationships in rhesus monkeys for a novel mixed-onium class of ultra-short-acting nondepolarizing tetrahydroisoquinolinium neuromuscular blockers (NMBs) are described. Bis-onium chlorofumarate 20a with (1R,2S)-benzyltetrahydroisoquinolinium groups was a potent lead compound (ED95 = 0.079 mg/kg) with an ultra-short duration of NMB effect (7.1 min) and a selectivity index (SI: defined as a ratio of the cardiovascular threshold dose to the ED95) similar to that of mivacurium (3). The mean threshold dose for cardiovascular effects with 20a was ca. 20 times its ED95 value (SI = 20). A novel mixed-onium analogue of 20a was prepared by replacing the benzyltetrahydroisoquinolinium group distal to the fumarate chlorine atom with a (1S,2R)-phenyltetrahydroisoquinolinium moiety. The resulting mixed-onium chlorofumarate 24a displayed good NMB potency (ED95 = 0.063 mg/kg), ultra-short duration of action (5.6 min) and an improved selectivity index (SI = 57). Several other mixed-onium derivatives containing octanedioate (25a; ED95 = 0.103 mg/kg), difluorosuccinate (27c; ED95 = 0.056 mg/kg), and fluorofumarate (28a; ED95 = 0.137 mg/kg) linkers were also potent, ultra-short-acting NMBs with good to excellent selectivity index values (SI = 37-96). Octanedioate 25a was longer acting at higher doses compared to difluorosuccinate 27c and chlorofumarate 24a. Durations of NMB effect following a 0.4 mg/kg bolus dose (100% block) of 25a, 27c, and 24a were 16.9, 13.0, and 10.0 min, respectively. Recovery time for mixed-onium chlorofumarate 24a following a 1 h continuous infusion at 10-20 mug/kg/min (95-100% block) was ca. 5 min which is similar to that observed following a 0.2 mg/kg bolus dose of this compound and indicates a lack of cummulative effects. Preliminary studies with chlorofumarate 24a in whole human blood revealed that mixed-onium thiazolidine 29 was the major metabolite and that plasma cholinesterases do not play the primary role in duration of NMB effect. The NMB properties of 24a in rhesus monkeys led to its clinical evaluation as a possible alternative to succinylcholine.