trans-(-)-(3R,4R)-3-amino-1-(4-methoxyphenyl)-4-phenylazetidin-2-one

• 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: trans-(-)-(3R,4R)-3-amino-1-(4-methoxyphenyl)-4-phenylazetidin-2-one
• 英文别名: trans-(3R,4R)-3-amino-1-(4-methoxyphenyl)-2-oxo-4-phenylazetidine；(3R,4R)-3-amino-1-(4-methoxyphenyl)-4-phenylazetidin-2-one
• 化学式: C₁₆H₁₆N₂O₂
• 分子量: 268.315
• InChiKey: XTSXQGSRHGCKDD-HUUCEWRRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  异硫氰酸己酯 、 trans-(-)-(3R,4R)-3-amino-1-(4-methoxyphenyl)-4-phenylazetidin-2-one 以 乙腈 为溶剂， 以54%的产率得到N-(n-hexyl)-N'-[trans-(3R,4R)-1-(4-methoxyphenyl)-2-oxo-4-phenylazetidin-3-yl]thiourea
  参考文献：
  名称：

  New Thiazolidinone and Triazinethione Conjugates Derived from Amino-β-lactams

  摘要：

  Thioureas 3a-s, generated from amino-beta-lactams 1a-c, were used to achieve two different cyclizations: (i) condensation with ethyl bromoacetate which resulted in the formation of a variety of iminothiazolidinones 4a/a'-n, and (ii) condensation with aqueous formaldehyde and methylamine which resulted in the formation of triazinethiones 5a-g. The condensation of thioureas 3b-f, 3h and 3m-s (R-1 = cyclohexyl, exo-norbornyl, aryl, R-2 = beta-lactam) with ethyl bromoacetate proceeded with high regioselectivity leading exclusively to the formation of a single regioisomer A of iminothiazolidinones 4b-n. However, the cyclization of thiourea 3a (R-1 = n-hexyl, R-2 = beta-lactam) with ethyl bromoacetate led to the formation of a mixture of two regioisomers A (minor) and B (major) of the iminothiazolidinones 4a/a' in the ratio 23:77. Furthermore, condensation of thioureas 3d, 3g, 3i-1 and 3n with aqueous formaldehyde and methylamine, furnished triazinethiones 5a-g.

  DOI：

  10.3987/com-09-11668
• 作为产物：
  描述：

  2-[1-(4-methoxyphenyl)-2-oxo-4-phenyl-azetidin-3-yl]isoindole-1,3-dione 在 乙二胺 作用下， 以 四氢呋喃 为溶剂， 以85%的产率得到trans-(-)-(3R,4R)-3-amino-1-(4-methoxyphenyl)-4-phenylazetidin-2-one
  参考文献：
  名称：

  Microwave-Induced Bismuth Nitrate-Catalyzed Michael Reaction of 3-Amino β-Lactams with Enones

  摘要：

  使用微波诱导的铋硝酸盐催化剂反应，将3-氨基β-内酰胺与不饱和酮反应，以获得取代的氨基β-内酰胺。氨基β-内酰胺是通过[2+2]烯酮-亚胺环加成策略获得，然后用乙二胺去保护邻苯二甲酰亚胺β-内酰胺。

  DOI：

  10.14233/ajchem.2020.22168

文献信息

• Synthesis of new steroid-β-lactam hybrids via palladium-catalyzed aminocarbonylation
  作者：János Balogh、Rita Skoda-Földes、Katarina Vazdar、Ivan Habuš

  DOI：10.1016/j.jorganchem.2011.12.033

  日期：2012.4

  Steroid-β-lactam and steroid-β-lactam-ferrocene conjugates were synthesized via palladium-catalyzed carbonylation of steroidal 17-iodo-16-enes in the presence of 3-amino-azetidin-2-ones. β-Lactam derivatives have been used for the first time as nucleophiles in the aminocarbonylation reaction. The products were obtained in good yields and were characterized by 1H and 13C NMR, IR and HRMS.

  在3-氨基氮杂环丁烷-2-酮的存在下，通过钯催化的甾族17-碘-16-烯的羰基化反应合成了甾体-β-内酰胺和甾体-β-内酰胺-二茂铁共轭物。β-内酰胺衍生物首次在氨基羰基化反应中用作亲核试剂。以高收率获得产物，并通过1 H和13 C NMR，IR和HRMS进行表征。
• Remarkable Iodine-Catalyzed Synthesis of Novel Pyrrole- Bearing N-Polyaromatic β-Lactams
  作者：Debasish Bandyopadhyay、Gildardo Rivera、Isabel Salinas、Hector Aguilar、Bimal K. Banik

  DOI：10.3390/molecules15021082

  日期：——

  Because of their interesting biological properties various methods for the synthesis of substituted pyrroles are described in the literature. However, synthesis of pyrroles fused with a β-lactam ring has not been reported. Our group has demonstrated synthesis and biological evaluation of various β-lactams as anticancer agents. The anticancer activities of these compounds have prompted us to study the synthesis of pyrroles bound to the β-lactams. We have identified an expeditious synthetic method for the preparation of pyrroles fused with β-lactams by reacting 3-amino β-lactams with acetonylacetone in the presence of catalytic amounts (5 mol%) of molecular iodine at room temperature. It has also been discovered that the reaction gives products under domestic and automated microwave oven irradiation. To our knowledge, there are no other prior reports that describe the synthesis of pyrrole-substituted β-lactams.

  由于其有趣的生物学特性，文献中描述了多种合成取代吡咯的方法。然而，尚未报道吡咯与β-内酰胺环融合的合成方法。我们的研究小组已经展示了多种β-内酰胺类化合物的合成及其作为抗癌剂的生物学评价。这些化合物的抗癌活性促使我们研究吡咯与β-内酰胺结合的合成方法。我们发现了一种高效的合成方法，通过在室温下使用催化量的分子碘（5 mol%）与3-氨基β-内酰胺和乙酰基丙酮反应，制备了与β-内酰胺融合的吡咯。此外，还发现该反应在家庭和自动化微波炉的照射下也能产生产品。据我们所知，没有其他先前的报告描述过吡咯取代的β-内酰胺的合成方法。
• A green, chemoselective, and practical approach toward N-(2-azetidinonyl) 2,5-disubstituted pyrroles
  作者：Debasish Bandyopadhyay、Elvira Rhodes、Bimal K. Banik

  DOI：10.1039/c3ra42266f

  日期：——

  practical method to synthesize novel N-(2-azetidinonyl) 2,5-disubstituted pyrroles, which are comprised of both pyrrole and 2-azetidinone moieties, has been developed. The classical Paal–Knorr reaction is one of the simplest and most economical methods for the synthesis of biologically important and pharmacologically useful pyrrole derivatives. The present procedure for the synthesis of N-(2-azetidinonyl) 2

  吡咯 和 2-氮杂环丁酮有两个重要的杂环支架，它们广泛用于药物化学和药物发现领域。一种合成新型N-（2-氮杂二壬基）2,5-二取代吡咯的绿色实用方法吡咯和2-氮杂环丁酮部分已被开发。经典的Paal–Knorr反应是合成生物学上重要且在药理上有用的吡咯衍生物的最简单，最经济的方法之一。N-（2-氮杂二壬基）2，5-二取代的吡咯（1,2,5-三取代的吡咯）的合成方法已经通过使3-氨基β-内酰胺与2,5-己二酮 在......的存在下 五水合硝酸铋在无溶剂条件下使用微波辐射作为一种环保催化剂。还比较了微波辅助条件和传统方法（在室温下搅拌）的效率。本方法对于具有化学敏感性官能团的N-聚芳族取代的β-内酰胺和光学纯的β-内酰胺同样有效。产品的结构和立体化学已通过广泛的光谱学和X射线晶体学分析得到了证实。本发明的合成N-（2-氮杂二壬基）2，5-二取代的吡咯的方法可用于开发有效的药理活性分子。
• Novel synthesis of 3-pyrrole substituted ?-lactams via microwave-induced bismuth nitrate-catalyzed reaction
  作者：Debasish Bandyopadhyay、Jessica Cruz、Bimal K. Banik

  DOI：10.1016/j.tet.2012.06.009

  日期：2012.12

  Highly stereoselective synthesis of 3-pyrrole substituted β-lactams is accomplished. The first step involves the synthesis of 3-phthalimido substituted β-lactams following Staudinger cycloaddition reaction of acid chloride equivalent with imines. Synthesis of 3-amino β-lactams is achieved via the deprotection of phthalimido group with ethylenediamine. These 3-amino β-lactams are converted to a new

  完成了3-吡咯取代的β-内酰胺的高度立体选择性合成。第一步涉及在酰基氯当量与亚胺的斯托丁格环加成反应之后，合成3-邻苯二甲酰亚胺基取代的β-内酰胺。3-氨基β-内酰胺的合成是通过用乙二胺将邻苯二甲酰亚胺基脱保护而实现的。这些3-氨基β-内酰胺在室温下以及使用微波诱导的硝酸铋催化的反应以优异的产率被转化为一系列新的N-取代的吡咯。用N- chrysenyl系统观察到反式吡咯取代的β-内酰胺的排他性形成。该方法对于合成外消旋以及光学纯的3-吡咯取代的β-内酰胺同样有效。
• Asymmetric synthesis of β-lactams by chiral ester enolate - imine condensation
  作者：Iwao Ojirna、Ivan I-Iabus

  DOI：10.1016/s0040-4039(00)97603-2

  日期：1990.1

  Asymmetric cyclocondensation of N,N-bis(silyl)glycinates bearing chiral ester moieties with aldimines is found to proceed with extremely high enantioselectivity to give the corresponding chiral β-lactams in good to high yields. It is found that the E/Z-geometry of the chiral ester-enolate ts responsible for cis/trans stereochemistry of the β-lactam formed. Effects of various chiral auxiliaries in the

  发现带有手性酯部分的N，N-双（甲硅烷基）甘氨酸酯与醛亚胺的不对称环缩合以极高的对映选择性进行，从而以良好或高收率得到相应的手性β-内酰胺。发现形成β-内酰胺的顺式/反式立体化学的手性酯-烯醇酸酯ts的E / Z-几何形状。考察了酯-烯酸酯中各种手性助剂对反应对映选择性的影响。