(2S,5S)-5-methyl-2-(iodomethyl)-4(2H)-dihydrofuranone | 139892-68-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧烷类
• 英文名称: (2S,5S)-5-methyl-2-(iodomethyl)-4(2H)-dihydrofuranone
• 英文别名: (2S,5S)-5-(iodomethyl)-2-methyloxolan-3-one
• CAS: 139892-68-5
• 化学式: C₆H₉IO₂
• 分子量: 240.041
• InChiKey: AWJUWTJXCXILLD-WHFBIAKZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (2S,5S)-5-methyl-2-(iodomethyl)-4(2H)-dihydrofuranone 在 sodium tetrahydroborate 、 dipotassium hydrogenphosphate 、 3α,20β-hydroxysteroid dehydrogenase 作用下， 以 乙醇 为溶剂， 反应 26.0h， 生成 (-)-Muscarine iodide
  参考文献：
  名称：

  Chemoenzymic synthesis of the eight stereoisomeric muscarines

  摘要：

  Efficient syntheses of the eight stereoisomers of muscarine have been accomplished by dehydrogenase-catalyzed reduction of iodo ketones (+/-)-3a and (+/-)-3b. 3-alpha,20-beta-Hydroxysteroid dehydrogenase from Streptomyces hydrogenans exhibited high enantiomeric and diastereotopic selectivity for (+/-)-3a, yielding an equimolar mixture of iodo alcohol (-)-4 (2S,4S,5S) (96% ee) and iodo ketone (+)-3a (2R,5R) (96% ee) which was reduced by sodium borohydride to a mixture of (+)-4 and (+)-5. 3-beta,17-beta-Hydroxysteroid dehydrogenase from Pseudomonas testosteroni reduced (+/-)-3b with high diastereotopic selectivity to give an equimolar mixture of iodo alcohols (+)-6 (2R,4S,5S) (> 99% ee) and (-)-7 (2S,4S,5R) (81% ee). Synthesis of the remaining iodo alcohols [(-)-5, (-)-6, and (+)-7] was achieved by applying the Mitsunobu procedure to (-)-4, (-)-7, and (+)-6. The enantiomeric excess of intermediates 4-7 was determined by HPLC analysis of the (R)-(+)-MTPA esters. The chiral iodo alcohols 4-7 were then transformed into the final derivatives by conventional chemical manipulations.

  DOI：

  10.1021/jo00001a015
• 作为产物：
  描述：

  (4S,5S)-5-(phenylmethoxy)hex-1-en-4-ol 在 碘 、 sodium acetate 、 pyridinium chlorochromate 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 (2S,5S)-5-methyl-2-(iodomethyl)-4(2H)-dihydrofuranone
  参考文献：
  名称：

  穆斯卡隆和异丁烯酮的对映异构体的合成及药理研究。

  摘要：

  基于使用（R）-和（S）-乳酸酯作为起始原料的策略，可以合成穆斯卡隆[（-）-1和（+）-1]和别甲香酮[（-）- 5和（+）-5]的对映体过量大于98％。检查了化合物与大脑皮层（M1），心脏（M2）和唾液腺（M3）的膜结合以及识别毒蕈碱受体亲和激动剂状态的能力。还通过五种功能测定法测试了两对对映异构体，并确定了它们的毒蕈碱效力。在结合力和功能测试中，（-）-1（2S，5S）和（-）-5（2R，5S）分别是穆斯卡隆和异源香豆素的体。在功能测试中评估的穆斯卡隆的普遍比例在280-440之间。这些值与（2.4-10。1）文献报道。从立体化学的观点来看，穆斯卡隆的行为与穆斯卡因和所有其他主要的毒蕈碱激动剂相同。结果，解释穆斯卡隆异常的假说不再存在。

  DOI：

  10.1021/jm00088a029

文献信息

• Synthesis and Pharmacological Characterization of Enantiomerically Pure Muscarinic Agonists:  Difluoromuscarines
  作者：Piero Angeli、Franco Cantalamessa、Roberto Cavagna、Paola Conti、Marco De Amici、Carlo De Micheli、Anna Gamba、Gabriella Marucci

  DOI：10.1021/jm960742w

  日期：1997.3.1

  The four homochiral 4-deoxy-4,4-difluoromuscarine stereoisomers (difluoromuscarines) were prepared in very high enantiomeric excess. A convenient sequence based on the use of natural as well. as ''unnatural'' ethyl lactate allowed the synthesis of target compounds, whose absolute configuration is dictated by that of the starting synthon. Quaternary ammonium salts (+)-5, (-)-5, (-)-6, and (+)-6 were tested in vitro on guinea pig tissues, and their muscarinic potency was evaluated at M(2) (heart) and M(3) (ileum and bladder) muscarinic receptor subtypes. The eutomer (+)-5 and distomer (-)-5 were also tested in vivo on pithed rat, and their muscarinic activity at the M(1) receptor subtype was compared with those of racemic muscarine [(+/-)-1] and (2S,4R,5S)-4-deoxy-4-fluoromuscarine [(+)-4]. Further pharmacological parameters such as affinity, relative efficacy, and enantioselectivity have been determined for compounds (+)-5 and (-)-5 at M(2) (heart force and rate) and M(3) (ileum and bladder) receptors in order to investigate muscarinic receptor heterogeneity. The four homochiral difluoromuscarines behave as muscarinic agonists in all the tests with a potency trend which is different from that previously observed with the 4-deoxy-4-fluoromuscarines and (+/-)-1, thus indicating the intervention of the second fluorine atom on the receptor-ligand interaction. Moreover, the second fluorine atom produces. significant differences in the affinity and relative efficacy values of compounds (+)-5 and (-)-5 at M(2) and M(3) subtypes, which could be attributed to a heterogeneity between the muscarinic receptors mediating heart rate and heart force and those involved in the contraction of ileum and bladder.
• De Amici; De Micheli; Gianferrara, Revista Bras il eira de Farmaco gnosia, 1993, vol. 48, # 10, p. 1349 - 1357
  作者：De Amici、De Micheli、Gianferrara、Grana、Dondi、Ladinsky、Schiavi

  DOI：——

  日期：——