(4R,5R,6S)-6-[(R)-1-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-3-(diphenoxy-phosphoryloxy)-4-methyl-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid allyl ester | 153471-17-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 英文名称: (4R,5R,6S)-6-[(R)-1-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-3-(diphenoxy-phosphoryloxy)-4-methyl-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid allyl ester
• 英文别名: prop-2-enyl (4R,5R,6S)-6-[(1R)-1-[tert-butyl(dimethyl)silyl]oxyethyl]-3-diphenoxyphosphoryloxy-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
• CAS: 153471-17-1
• 化学式: C₃₁H₄₀NO₈PSi
• 分子量: 613.72
• InChiKey: WLHMJGSPRRBGEP-SAZLYLDSSA-N

物化性质

• 沸点：
  621.9±55.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  42
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (4R,5R,6S)-6-[(R)-1-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-3-(diphenoxy-phosphoryloxy)-4-methyl-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid allyl ester 在 盐酸 、 甲醇 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 12.0h， 以95.5%的产率得到allyl (1R,5R,6S)-2-(diphenoxyphosphoryloxy)-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate
  参考文献：
  名称：

  一种碳青霉烯类抗生素母核MPP的合成方法

  摘要：

  本发明公开了一种碳青霉烯类抗生素母核MPP的合成方法。与现有技术相比，本发明重新设计了一条MPP的合成路线，提高了合成效率，并且反应原料价格较低，反应条件不苛刻，相对降低了能耗和成本，同时，收率提高至62％以上。

  公开号：

  CN105061507B
• 作为产物：
  描述：

  烯丙基2-溴乙酸乙酯 在 三甲基氯硅烷 、 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 17.92h， 生成 (4R,5R,6S)-6-[(R)-1-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-3-(diphenoxy-phosphoryloxy)-4-methyl-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid allyl ester
  参考文献：
  名称：

  2-取代的2,3-二氢-4H-1,3-苯并恶嗪-4-酮类化合物：立体选择性合成1-β-甲基卡宾烯的新型助剂（1）。

  摘要：

  容易由水杨酰胺11和环己酮制得的二氢苯并恶唑酮9e在合成1-β-甲基卡巴培南关键中间体10时用作有效的助剂。乙酰氧基氮杂环丁酮2与羧酰亚胺6的立体控制的Reformatsky型反应得到了中间体7具有高非对映选择性，化学收率高。辅助9e在TMSC1促进的Dieckmann型环化中还充当良好的离去基团，导致1-β-甲基卡巴培南骨架。通过使用该助剂，合成了10种化合物，总产率为58％，从2开始需四个步骤。

  DOI：

  10.1021/jo961866j

文献信息

• 2-Substituted 2,3-Dihydro-4<i>H</i>-1,3-benzoxazin-4-ones:  Novel Auxiliaries for Stereoselective Synthesis of 1-β-Methylcarbapenems¹
  作者：Kazuhiko Kondo、Masahiko Seki、Tooru Kuroda、Takeshi Yamanaka、Tameo Iwasaki

  DOI：10.1021/jo961866j

  日期：1997.5.1

  The dihydrobenzoxazone 9e, which is easily prepared from salicylamide 11 and cyclohexanone, serves as an efficient auxiliary in the synthesis of the 1-beta-methylcarbapenem key intermediate 10. The stereocontrolled Reformatsky-type reactions of the acetoxyazetidinone 2 with the carboximides 6 gave the intermediates 7 with high diastereoselectivities in high chemical yields. The auxiliary 9e also acts

  容易由水杨酰胺11和环己酮制得的二氢苯并恶唑酮9e在合成1-β-甲基卡巴培南关键中间体10时用作有效的助剂。乙酰氧基氮杂环丁酮2与羧酰亚胺6的立体控制的Reformatsky型反应得到了中间体7具有高非对映选择性，化学收率高。辅助9e在TMSC1促进的Dieckmann型环化中还充当良好的离去基团，导致1-β-甲基卡巴培南骨架。通过使用该助剂，合成了10种化合物，总产率为58％，从2开始需四个步骤。
• Practical Synthesis of (<i>R</i>)-4-Mercaptopyrrolidine-2-thione from <scp>l</scp>-Aspartic Acid. Preparation of a Novel Orally Active 1-β-Methylcarbapenem, TA-949
  作者：Masahiko Seki、Takeshi Yamanaka、Kazuhiko Kondo

  DOI：10.1021/jo991461+

  日期：2000.1.1

  High-yield amination and cyclization of the chloride 15 to the pyrrolidin-2-one 16 was accomplished by a simple treatment with ammonia. Thiation of 16 and the Birch reduction of the resultant thiolactam 18 provided the C-2 side chain 2 in high yield with the asymmetric center retained as such. The side chain 2 was installed into the 1-beta-methylcarbapenem skeleton either by coupling with the vinyl phosphate

  描述了一种新型的口服活性1-β-甲基卡巴培南TA-949（1）的简便经济合成方法。关键过程涉及从L-天冬氨酸有效合成C-2侧链（R）-4-巯基吡咯烷-2-硫酮2和1-β-甲基卡巴培南骨架的构建。通过将L-天冬氨酸β-甲基酯盐酸盐12的氨基脱氨基溴化，然后用苯甲硫醇钾进行完全S（N）2型取代，形成具有R-构型的2巯基。通过用氨进行简单处理，可以将氯化物15高产率地胺化和环化为吡咯烷酮-2-酮16。16的硫杂化和所得硫代内酰胺18的桦木还原提供了高收率的C-2侧链2，并保留了不对称中心。
• Synthesis and antibacterial activity of novel 4-pyrrolidinylthio carbapenems—I. 2-alkoxymethyl derivatives
  作者：Hidenori Azami、Hideo Tsutsumi、Keiji Matsuda、David Barrett、Kouji Hattori、Takashi Nakajima、Satoru Kuroda、Toshiaki Kamimura、Masayoshi Murata

  DOI：10.1016/s0968-0896(97)00142-9

  日期：1997.11

  The synthesis and in vitro antibacterial activity of a novel series of 2-alkoxymethyl-4-pyrrolidinylthio-1 beta-methyl carbapenems are described. As a result of these studies, we discovered that FR27743 (19j) containing a novel,2-fluoroethoxymethyl substituent possesses a broad spectrum of antibacterial activity against both Gram-positive and Gram-negative organisms, including Pseudomonas aeruginosa. Furthermore, FR27743 exhibited excellent stability against renal dehydropeptidase-I (DHP-I), good urinary recovery, and superior in vivo activity compared to that for Meropenem against several systemic infections. (C) 1997 Elsevier Science Ltd.
• Efficient synthesis of 1β-methylcarbapenems based on the counter-attack strategy
  作者：Masahiko Seki、Kazuhiko Kondo、Tameo Iwasaki

  DOI：10.1039/p19960002851

  日期：——

  A seven-step efficient synthesis of 1 beta-methylcarbapenems 1 from the acetoxyazetidinone 6 is described. The Reformatsky reaction of 3-(2-bromopropionyl)-1,3-benzoxazinone 7 with compound 6 gave an adduct 8 in 96% yield with high beta-selectivity (beta:alpha = 92:8). Compound 8 was transformed in three steps into the side-chain thiol esters 12a-e in good yields. The chlorotrimethylsilane-mediated Dieckmann-type cyclisation of thioesters 12b-e followed by counter-attack of the liberated thiolate anion 18 yielded the C-2 alkylthio- or arylthio-substituted 1 beta-methylcarbapenems 19b-e in a one-pot procedure. The synthesis of 1 beta-methylcarbapenems 1 was demonstrated by a simple cleavage of the silyl ether and allyl ester of compound 19b to afford target compound 1b in high yield.
• A New Synthesis of 1β-Alkylcarbapenems Utilizing Eschenmoser Sulfide Contraction of the Novel Thiazinone Intermediates
  作者：Osamu Sakurai、Tsuyoshi Ogiku、Masami Takahashi、Masahito Hayashi、Takeshi Yamanaka、Hiroshi Horikawa、Tameo Iwasaki

  DOI：10.1021/jo960764q

  日期：1996.1.1

  Novel syntheses of the 1,beta-alkylcarbapenems were achieved on the basis of Eschenmoser sulfide contraction via the new bicyclic 1,3-thiazinone intermediates. 1,3-Thiazinones 7, 16, and 25 were effectively prepared from thioesters 5 and 22 using a C4-S bond formation process. The sulfide contraction reactions were performed by treatment of 7, 16, and 25 with base (NaH or KO-t-Bu) in the presence of triphenylphosphine to generate the corresponding carbapenem enolate 12, 17, and 26, which were trapped by (PhO)(2)POCl followed by the reaction with mercaptans to afford carbapenems 10a, 10b, 19, and 28, respectively.