(S)-3-(Acetylthio)thiolane 1(R)-oxide | 120788-03-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 硫杂环戊烷
• 英文名称: (S)-3-(Acetylthio)thiolane 1(R)-oxide
• 英文别名: 3S-(acetylthio)thiolane 1R-oxide；3S-(acetylthio)thiolane-1R-oxide；S-[(1R,3S)-1-oxothiolan-3-yl] ethanethioate
• CAS: 120788-03-6
• 化学式: C₆H₁₀O₂S₂
• 分子量: 178.276
• InChiKey: JZXIAFHBEMXBJY-QUBYGPBYSA-N

物化性质

• 沸点：
  375.3±22.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  78.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-3-(Acetylthio)thiolane 1(R)-oxide 在 sodium ethanolate 作用下， 以 乙醇 、 醋酸异丙酯 为溶剂， 反应 0.5h， 生成 (1R,3S)-1-oxothiolane-3-thiol
  参考文献：
  名称：

  Development of a Practical and Convergent Process for the Preparation of Sulopenem

  摘要：

  Previous synthetic processes for the preparation of sulopenem involved multistep linear sequences in which the chiral sulfoxide side chain was introduced early in the process. This contribution summarizes the development of a practical and convergent process for the large-scale preparation of 1. The key step in the synthesis involves cyclization of an oxalimide intermediate to provide the thiopenem core. This convergent strategy allows for late introduction of the expensive and labile chiral sulfoxide subunit. Additionally, a regioselective sulfur oxidation and an improved deprotection sequence were developed. The latter provides API of high purity without the need for recrystallization.

  DOI：

  10.1021/op300131e
• 作为产物：
  描述：

  (R)-3-<(p-Toluenesulfonyl)oxy>thiolane 1(R)-oxide 、 potassium thioacetate 以 丙酮 为溶剂， 以80%的产率得到(S)-3-(Acetylthio)thiolane 1(R)-oxide
  参考文献：
  名称：

  硫培南侧链的合成方法

  摘要：

  本发明公开了一种硫培南侧链的合成方法。该合成方法包括以下步骤：以为原料采用酮还原酶还原生成进而通过单加氧酶氧化生成对进行对甲苯磺酰基保护后，再通过硫酰基保护得到目标产物应用本发明的技术方案，使用酮还原酶和单加氧酶，分别进行第一步和第二步两步生物转化，再将第二步氧化产物进行Ts(对甲苯磺酰基)保护后，最后通过硫酰基保护得到目标产物，由于第一步和第二步均为生物转化，不需要通过乙酸乙酯萃取，减少了乙酸乙酯的用量。

  公开号：

  CN109796434B

文献信息

• [EN] DIASTEREOMERIC 5R,6S-6-(1R-HYDROXYETHYL)-2-(CIS-1-OXO-3-THIOLANYLTHIO)-2-PENEM-3-CARBOXYLIC ACIDS
  申请人：PFIZER INC.

  公开号：WO1988008845A1

  公开（公告）日：1988-11-17

  (EN) Diastereomeric 5R,6S-6-(1R-hydroxyethyl)-2-(1S-oxo-3R-thiolanylthio)-2-penem-3-carboxylic acid and 5R,6S-6-(1R-hydroxyethyl)-2-(1R-oxo-3S-thiolanylthio)-2-penem-3-carboxylic acid, and pharmaceutically-acceptable salts and $i(in vivo) hydrolyzable esters thereof, useful as systemic antibacterial agents; and intermediates and processes which are useful in the said synthesis of said diastereoisomers.(FR) Acide diastéréomère 5R,6S-6-(1R-hydoxyéthyle)-2-(1S-oxo-3-R-thiolanylthio)-2-penem-3-carboxylique et acide 5R,6S-6-(1R-hydroxyéthyle)-2-(1R-oxo-3S-thiolanylthio)-2-penem-3-carboxylique, des sels pharmaceutiquement acceptables et leurs esters hydrolysables $i(in vivo), utiles à titre d'agents antibactériens du système, des agents intermédiaires et des procédés ayant une utilité dans ladite synthèse desdits diastéréoisomères.

  (中文翻译) 所述的对映异构体5R,6S-6-(1R-羟乙基)-2-(1S-氧代-3R-硫代基硫基)-2-青霉烷-3-羧酸和5R,6S-6-(1R-羟乙基)-2-(1R-氧代-3S-硫代基硫基)-2-青霉烷-3-羧酸，以及其药学上可接受的盐和在体内可水解的酯，可用作全身抗菌剂；以及在所述对映异构体的合成中有用的中间体和工艺。
• 2-Alkylthiopenem derivatives
  申请人：PFIZER INC.

  公开号：EP0130025A1

  公开（公告）日：1985-01-02

  2-alkylthio-2-penem-3- carboxylic acid compounds, useful as antibacterials for treating mammals, have the formula: or a pharmaceutically acceptable salt thereof, wherein: R is 2-(methylsulfinyl) ethyl, 2-(methylsulfonyl)- ethyl, (methylsulfinyl)methyl, (methylsulfonyl)methyl, 3-thietanyl, 1-oxo-3-thietanyl, 1,1-dioxo-3-thietanyl, 2-thiolanyl, 1-oxo-2-thiolanyl, 3-thiolanyl, 1-oxo-3-thiolanyl, 1,1-dioxo-3-thiolanyl, 3-hydroxy-4-thiolanyl, 1-oxo-3-hydroxy-thiolanyl, 1, 1-dioxo-3-hydroxy-4-thiolanyl, 2-oxo-1, 3-dithiolan, 4-ylmethyl, 3-thianyl, 1-oxo-3-thianyl, 1, 1-dioxo-3-thianyl, 4-thianyl, 1-oxo-4-thianyl, 1, 1-dioxo-4-thianyl, 3-oxo-perhydro-1, 4-thiazin-2-yl. 4-formylperhydro-1, 4-thiazin-2-yl, 4-oxo-1, 4-oxathian-3-yl, 4, 4-dioxo-1, 4-oxathian-3-yl, 1, 3-dithiolan-2-yl, 1, 2-dithiolan-4-yl, or (2-methyl-3, 3-dioxo-1, 3-oxathiolan-5-yl) methyl; and R, is hydrogen or a group which forms an ester which is hydrolyzed in vivo.

  作为治疗哺乳动物的抗菌剂的 2-烷硫基-2-烯-3-羧酸化合物具有以下式子： 或其药学上可接受的盐，其中 R是 2-(甲磺酰)乙基、2-(甲磺酰)-乙基、(甲磺酰)甲基、(甲磺酰)甲基、3-硫杂环丁烷、1-氧代-3-硫杂环丁烷、1,1-二氧代-3-硫杂环丁烷、2-硫杂环丁烷、1-氧代-2-硫杂环丁烷、3-硫杂环丁烷、1-氧代-3-硫杂环丁烷、1,1-二氧代-3-硫杂环丁烷、3-hydroxy-4-thiolanyl, 1-oxo-3-hydroxy-thiolanyl, 1, 1-dioxo-3-hydroxy-4-thiolanyl, 2-oxo-1, 3-dithiolan, 4-ylmethyl, 3-thianyl, 1-oxo-3-thianyl, 1, 1-dioxo-3-thianyl, 4-thianyl, 1-oxo-4-thianyl, 1, 1-dioxo-4-thianyl, 3-oxo perhydro-1, 4-thiazin-2-yl.4-甲酰过氢-1，4-噻嗪-2-基，4-氧代-1，4-氧硫杂环戊-3-基，4，4-二氧代-1，4-氧硫杂环戊-3-基，1，3-二硫环戊-2-基，1，2-二硫环戊-4-基，或（2-甲基-3，3-二氧代-1，3-氧硫杂环戊-5-基）甲基；以及 R，是氢或可形成在体内水解的酯的基团。
• Diastereomeric 5R,6S-6-(1R-hydroxyethyl)-2-(cis-1-oxo-3-thiolanylthio)-2-penem-3-carboxylic acids
  申请人：PFIZER INC.

  公开号：EP0294934A2

  公开（公告）日：1988-12-14

  Diastereomeric 5R,6S-6-(1R-hydroxyethyl)-2-(1S-oxo-­3R-thiolanylthio)-2-penem-3-carboxylic acid and 5R,6S-­6-(1R-hydroxyethyl)-2-(1R-oxo-3S-thiolanylthio)-2-penem-­3-carboxylic acid, and pharmaceutically-acceptable salts and in vivo hydrolyzable esters thereof, useful as systemic antibacterial agents; and intermediates and processes which are useful in the said synthesis of said diastereoisomers.

  非对映异构体 5R,6S-6-(1R-羟乙基)-2-(1S-氧代-3R-硫代巯基)-2-青霉烯-3-羧酸和 5R,6S-6-(1R-羟乙基)-2-(1R-氧代-3S-硫代巯基)-2-青霉烯-3-羧酸，及其药学上可接受的盐类和体内可水解的酯类，可用作全身抗菌剂；以及用于合成上述非对映异构体的中间体和工艺。
• 2-Thioalkyl penems: an efficient synthesis of sulopenem, a (5R,6S)-6-(1(R)-hydroxyethyl)-2-[(cis-1-oxo-3-thiolanyl)thio]-2-penem antibacterial
  作者：Robert A. Volkmann、Paul R. Kelbaugh、Deane M. Nason、V. John Jasys

  DOI：10.1021/jo00042a010

  日期：1992.7

  A practical synthesis of potent penem antibacterials, CP-70,429 (1) (sulopenem) and CP-81,054 (2), is described. (L)-Aspartic acid was utilized to generate both the (3S)- and (3R)-thiolanylthio side chains of (5R,6S)-6-(1-(R)-hydroxyethyl)-2-[(cis-1-oxo-3-thiolanyl)thio]-2-penem-3-carboxylic acids 1 and 2. This synthetic pathway provided in high yield enantiopure thioacetate intermediates 15 and 19. To accommodate the fragile side chain sulfoxide moiety of the targeted beta-lactams, standard penem synthetic methodology was modified to facilitate the conversion of 15 and 19 to 1 and 2. The reactive chloroazetidinone 4b was utilized to generate key azetidinone trithiocarbonate intermediate 22 which contains the requisite penem side chain. A chemoselective oxalofluoride-based azetidinone N-acylation procedure, which avoids sulfoxide O-acylation, was required for the conversion of 22 to the penem framework.
• VOLKMANN, ROBERT A.
  作者：VOLKMANN, ROBERT A.

  DOI：——

  日期：——