methyl (2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenoxyacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate | 2315-05-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: methyl (2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenoxyacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate
• 英文别名: penicillin V methyl ester；phenoxymethylpenicillin methyl ester；6-(Phenoxyacetyl-amino)-penicillansaeure-methylester；4-Thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid, 3,3-dimethyl-7-oxo-6-(phenoxyacetamido)-, methyl ester；methyl (2S,5R,6R)-3,3-dimethyl-7-oxo-6-[(2-phenoxyacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate
• CAS: 2315-05-1
• 化学式: C₁₇H₂₀N₂O₅S
• 分子量: 364.422
• InChiKey: JYVSRPXYJNDSQP-VNHYZAJKSA-N

物化性质

• 沸点：
  609.0±55.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl (2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenoxyacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate 在 periodate form of Amberlyst A₂₆ 作用下， 以 甲醇 为溶剂， 反应 18.0h， 以89%的产率得到1α-oxo-6β-(2-phenoxy-acetylamino)-1λ⁴-penicillanic acid methyl ester
  参考文献：
  名称：

  Harrison, Charles R.; Hodge, Philip, Journal of the Chemical Society. Perkin transactions I, 1982, p. 509 - 511

  摘要：

  DOI：
• 作为产物：
  描述：

  苯氧乙酰氯 在 碳酸氢钠 作用下， 以 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 1.33h， 生成 methyl (2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenoxyacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate
  参考文献：
  名称：

  合成新的作为药物样分子的青霉素衍生物，用于生物筛选

  摘要：

  摘要对青霉素β-内酰胺环进行了化学修饰。通过青霉素V甲酯的N4-C7β-内酰胺开环，与各种脂肪族，芳香族和杂环伯胺生成六种噻唑烷酰胺。通过β-内酰胺环重排，由6-氨基青霉酸（6-APA）得到五个具有甲基，丙基，苄基和二乙基氨基乙基侧链的8-羟基青霉酸衍生物。采用平行合成方法对8-羟基青霉烯酸进行烷基化，使青霉素V甲酯的β-内酰胺开环。评价了化合物的生物活性。

  DOI：

  10.1016/j.cclet.2014.09.008

文献信息

• Alkylating Polymers: Resin-Released Carbenium Ions as Versatile Reactive Intermediates in Polymer-Assisted Solution-Phase Synthesis
  作者：Jörg Rademann、Joachim Smerdka、Günther Jung、Philipp Grosche、Dietmar Schmid

  DOI：10.1002/1521-3773(20010119)40:2<381::aid-anie381>3.0.co;2-v

  日期：2001.1.19

  Solid-supported diazoalkane analogues for the smooth and clean esterifications of carboxylic acids [Eq. (1)] as well as of complex compound mixtures: the alkylating polymers presented here were synthesized as solid-supported 3-alkyl-1-aryltriazenes and are capable of releasing carbenium ions following acidic activation.

  固体负载的重氮烷烃类似物，用于羧酸的平滑和清洁酯化反应[式]。（1）]以及复杂的化合物混合物：此处介绍的烷基化聚合物是作为固体负载的3-烷基-1-芳基三氮烯合成的，能够在酸性活化后释放碳正离子。
• [EN] CEPHALOSPORIN DERIVATIVES AND METHODS OF USE<br/>[FR] DÉRIVÉS DE CÉPHALOSPORINE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：UNIV KANSAS

  公开号：WO2014071283A1

  公开（公告）日：2014-05-08

  This invention provides cephalosporin derivatives for killing or inhibiting the spread of microorganisms such as non-replicating Mycobacterium tuberculosis and in the treatment of infectious disease.

  这项发明提供了头孢菌素衍生物，用于杀灭或抑制微生物的传播，如非复制的结核分枝杆菌，并用于治疗传染病。
• Synthesis and decarboxylation of Δ²-cephem-4,4-dicarboxylic acids
  作者：Saul Wolfe、Stephen Ro、Chan-Kyung Kim、Zheng Shi

  DOI：10.1139/v01-100

  日期：2001.8.1

  Penicillin V was converted in 14 steps into Δ²-cephems having hydrogen at C-3, hydrogen or ethyl at C-2, and two methoxycarbonyl, two benzyloxycarbonyl, or one methoxycarbonyl and one benzyloxycarbonyl substituent at C-4. Deprotection of these Δ²-cephem-4,4-dicarboxylic acid esters by alkaline hydrolysis (in the case of methyl esters) or hydrogenolysis (in the case of benzyl esters) led in all cases to rapid decarboxylation of the Δ²-cephem-4,4-dicarboxylic acid or Δ²-cephem-4,4-dicarboxylic acid monoester. With hydrogen at C-2, hydrolysis of the dimethyl ester with 1 equiv of base produced a Δ²-cephem. With 2 equiv of base, and with all compounds having methyl at C-2, hydrolysis or hydrogenolysis afforded 4α-substituted-Δ²-cephems.

  In contrast, simpler benzyl or methyl acetamidomalonates could be deprotected without difficulty to afford stable malonic acids. Reasons for the differences in ease of decarboxylation were examined using semiempirical (AM1) and ab initio (3-21G) molecular orbital calculations. The decarboxylation barriers of unionized cephem or acetamido malonic acids were found to be high (35–40 kcal mol^–1). Although the monoanion of acetamidomalonic acid retained a high barrier, the epimeric monoanions of a Δ²-cephem malonic acid decarboxylated with barriers of only 2 kcal mol^–1.Key words: mercaptoazetidinone, bromomalonate esters, MO calculations, sulfoxides, hydrogenolysis.

  青霉素V经过14个步骤转化为具有C-3处氢、C-2处氢或乙基，以及C-4处两个甲氧羰基、两个苄氧羰基或一个甲氧羰基和一个苄氧羰基取代基的Δ2-头孢菌素。通过碱性水解（对甲酯类）或氢解（对苄酯类）去保护这些Δ2-头孢菌素-4,4-二羧酸酯，在所有情况下都导致Δ2-头孢菌素-4,4-二羧酸或Δ2-头孢菌素-4,4-二羧酸单酯的快速脱羧。C-2处为氢时，用1当量碱水解二甲酯酯类产生Δ2-头孢菌素。用2当量碱，并且所有化合物C-2处为甲基时，水解或氢解得到4α-取代的Δ2-头孢菌素。 相比之下，更简单的苄或甲基乙酰胺丙二酸酯可以轻松去保护以得到稳定的丙二酸。使用半经验（AM1）和从头算（3-21G）分子轨道计算研究了脱羧难易度差异的原因。发现未离子化的头孢菌素或乙酰胺丙二酸的脱羧能垒较高（35-40 kcal mol-1）。尽管乙酰胺丙二酸的单负离子保留了较高的能垒，但Δ2-头孢菌素丙二酸的异构单负离子脱羧能垒仅为2 kcal mol-1。关键词：巯基氮杂环丙酮酮，溴丙二酸酯，分子轨道计算，亚氧化物，氢解。
• Conversion of 6α-alkoxyformamidopenicillanates into 6α-aminopenicillanates, and the formation of 6-spiropenicillanates
  作者：David H. Bremner、Malcolm M. Campbell、Graham Johnson

  DOI：10.1039/c39760000293

  日期：——

  Methyl 6β-phenoxyacetamido-6α-trichloroethoxyformamidopenicillanate has been converted into a 6α-aminopenicillanate; 6α-ethoxyformamido-6β-phenoxyacetamidopenicillanates reacted with phosgene and base to afford unique (1-ethoxycarbonyl-3-phenoxyacetyl-2-oxo-1,3-diazetidine)-4-spiro-6′-penicillanates.

  6- β -phenoxyacetamido-6 α -trichloroethoxyformamidopenicillanate已被转换成一个6 α -aminopenicillanate; 6 α -ethoxyformamido-6 β -phenoxyacetamidopenicillanates与光气和碱反应，得到独特的（1-乙氧羰基-3-苯氧基-2-氧代-1,3-二氮杂环丁烷）-4-螺-6'- penicillanates。
• Penicillin biosynthesis: direct biosynthetic formation of penicillin V and penicillin G
  作者：Jack E. Baldwin、Edward P. Abraham、Geoffrey L. Burge、Hong-Hoi Ting

  DOI：10.1039/c39850001808

  日期：——

  The enzyme isopenicillin N synthetase is able to convert directly the dipeptides, phenoxyacetylcysteinylvaline and phenylacetylcysteinylvaline into penicillin V and G respectively; these are however very slow compared with substrates of the α-aminoadipoyl or adipoylcysteinylvaline type.

  异青霉素N合成酶能够直接将二肽，苯氧基乙酰半胱氨酸缬氨酸和苯基乙酰半胱氨酸缬氨酸分别转化为青霉素V和G。然而，与α-氨基己二酰基或己二酰基半胱氨酸缬氨酸类型的底物相比，它们非常慢。