methyl (-)(2S,5S)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate | 110583-01-2

• 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: methyl (-)(2S,5S)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate
• 英文别名: methyl penicillanate；methyl (2S,5S)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate
• CAS: 110583-01-2
• 化学式: C₉H₁₃NO₃S
• 分子量: 215.273
• InChiKey: DJANLSNABDFZLA-BQBZGAKWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  71.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  D-青霉胺 在 甲酸 、 四丁基硫酸氢铵 、 potassium hydrogencarbonate 、 甲基磺酰氯 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 、 氯仿 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 141.5h， 生成 methyl (-)(2S,5S)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate
  参考文献：
  名称：

  The formylacetate synthon. Studies related to the synthesis of the penam and oxapenam ring systems

  摘要：

  甲基青霉酸已通过D-青霉胺与三种不同变体的合成子RO₂CCH₂CHO缩合而成，随后通过酯化生成的4-羧基噻唑啉-2-乙酸酯，去除R，并进行向山环闭合。已确定了含有N-苯甲酰保护基的类似4-羧基噁唑啉-2-乙酸酯的合成条件。苏氨酸与二乙炔酮的缩合不会直接导致烯丙基氧青霉酮的形成。

  DOI：

  10.1139/v87-006

文献信息

• Studies on amino acid derivatives. IX. Synthesis of chiral penam-3-carboxylic acid and its substituted derivatives.
  作者：Takuo CHIBA、Jun-ichi SAKAKI、Satoshi KOBAYASHI、Toshio FURUYA、Noriyoshi INUKAI、Chikara KANEKO

  DOI：10.1248/cpb.37.877

  日期：——

  Methyl penam-(3S)-carboxylate (methyl 7-oxo-1-thia-4-azabicyclo[3.2.0]heptane-(3S)-carboxylate), the basic skeleton of penicillin-type β-lactams, has been synthesized from D-cysteine methyl ester and tert-butyl formylacetate in three steps through the formation of the thiazolidinylacetic acid followed by cyclization by Mukaiyama-Ohno's procedure. Use of D-penicillamine methyl ester as well as the dimethyl derivative of tert-butyl formylacetate in the above method provides a general synthetic route to a variety of methyl penam-(3S)-carboxylates having methyl groups at the 2 and/or 6-positions.The yields as well as stereoselectivity at C-5 in the cyclization step are shown to be strongly dependent upon the patterns of substituents on the thiazolidinylacetic acid skeleton, and the reason for this is discussed from the mechanistic viewpoint.

  青霉素类 β-内酰胺的基本骨架--五南-(3S)-羧酸甲酯（7-氧代-1-硫杂-4-氮杂双环[3.2.0]庚烷-(3S)-羧酸甲酯），是由 D-半胱氨酸甲酯和甲酰乙酸叔丁酯，通过 Mukaiyama-Ohno 程序，先形成噻唑烷基乙酸，再环化，分三步合成的。在上述方法中使用 D-青霉胺甲酯以及甲酰乙酸叔丁酯的二甲基衍生物，为在 2 位和/或 6 位上具有甲基的各种戊-(3S)-羧酸甲酯提供了一条通用的合成路线。研究表明，环化步骤中 C-5 位的产量和立体选择性与噻唑烷基乙酸骨架上的取代基形态密切相关，并从机理的角度讨论了其中的原因。
• Syntheses of (6S)-Cephalosporins from 6-Aminopenicillanic Acid
  作者：Tomasz Fekner、Jack E Baldwin、Robert M Adlington、Timothy W Jones、C.Keith Prout、Christopher J Schofield

  DOI：10.1016/s0040-4020(00)00486-5

  日期：2000.8

  Two practical routes to (6S,7S)-cephalosporins from 6-aminopenicillanic acid (6-APA) are described. In the first, 6-APA was converted to (2S,4S,5S,6S)-penicillin sulfoxide 49, which underwent Morin ring expansion to a protected (6S,7S)-cephem 50. In the second, ester 15 was converted to (2S,4S,5S,6R)-penicillin sulfoxide 58, which was then transformed into (6S,7R)-cephem 59. Different methods for the epimerisation of the C-7 position of cephem 59 were examined. (C) 2000 Elsevier Science Ltd. All rights reserved.
• CHIBA, TAKUO;SAKAKI, JUN-ICHI;KOBAYASHI, SATOSHI;FUKUYA, TOSHIO;INUKAI, N+, CHEM. AND PHARM. BULL., 37,(1989) N, C. 877-882
  作者：CHIBA, TAKUO、SAKAKI, JUN-ICHI、KOBAYASHI, SATOSHI、FUKUYA, TOSHIO、INUKAI, N+

  DOI：——

  日期：——
• The formylacetate synthon. Studies related to the synthesis of the penam and oxapenam ring systems
  作者：Saul Wolfe、Roman Z. Sterzycki

  DOI：10.1139/v87-006

  日期：1987.1.1

  Methyl penicillanate has been synthesized by condensation of D-penicillamine with three different variations of the synthon RO₂CCH₂CHO, followed by esterification of the resulting 4-carboxythiazolidine-2-acetic acid ester, removal of R, and Mukaiyama ring closure. The conditions for the synthesis of an analogous 4-carboxyoxazolidine-2-acetic acid ester, containing an N-benzoyl protecting group, have been worked out. The condensation of threonine with diethinylketone does not lead directly to a vinylogous oxapenam.

  甲基青霉酸已通过D-青霉胺与三种不同变体的合成子RO₂CCH₂CHO缩合而成，随后通过酯化生成的4-羧基噻唑啉-2-乙酸酯，去除R，并进行向山环闭合。已确定了含有N-苯甲酰保护基的类似4-羧基噁唑啉-2-乙酸酯的合成条件。苏氨酸与二乙炔酮的缩合不会直接导致烯丙基氧青霉酮的形成。