(+)-(3R,4R)-1-(p-anisyl)-3-benzyloxy-4-formyl-2-azetidinone | 148968-08-5

• 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: (+)-(3R,4R)-1-(p-anisyl)-3-benzyloxy-4-formyl-2-azetidinone
• 英文别名: (+)-cis-1-(p-methoxyphenyl)-3-benzyloxy-4-formyl-2-azetidinone；(3R,4R)-1-(4-methoxyphenyl)-3-benzyloxy-4-formyl-2-azetidinone；(3R,4R)-3-benzyloxy-1-(4-methoxyphenyl)-4-formylazetidin-2-one；(2R,3R)-1-(4-methoxyphenyl)-4-oxo-3-phenylmethoxyazetidine-2-carbaldehyde
• CAS: 148968-08-5
• 化学式: C₁₈H₁₇NO₄
• 分子量: 311.337
• InChiKey: HWWJMIJPXNRDOH-DLBZAZTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+)-(3R,4R)-1-(p-anisyl)-3-benzyloxy-4-formyl-2-azetidinone 在 magnesium sulfate 、 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 3.0h， 生成 [(2S,3R)-1-(4-methoxyphenyl)-2-[(2S,3R)-1-(4-methoxyphenyl)-4-oxo-3-phenylmethoxyazetidin-2-yl]-4-oxoazetidin-3-yl] acetate
  参考文献：
  名称：

  C4,C4‘-Bis-β-lactam to Fused Bis-γ-lactam Rearrangement

  摘要：

  Optically pure cis,cis-C4,C4'-bis-beta-lactams 1a-d are obtained in good to excellent yields, in a single step, following two different approaches. Staudinger reaction of (S)-(4-phenyl-2-oxooxazolidinyl)acetyl chloride (2a) and p-anisyldiimine gave the corresponding bis-beta-lactam la as a single enantiomer. The reaction of glyoxal diimine derived from (S)-alpha-phenylethylamine and different alkoxy-substituted acid chlorides gave diastereomeric mixtures of cis,cis-bis-beta-lactams 1b-d, enantiomers at the bicyclic skeleton. The configuration of all compounds has been determined by X-ray diffraction analysis of enantiomerically pure aldehyde 4a and bis-beta-lactam Ib-a. The remaining bicyclic lactams have been chemically correlated to compound 1b-alpha and their configurations assigned. Starting from enantiomerically pure 4-formyl-2-azetidinone 4b, sequential imine formation and ketene cycloaddition allowed the synthesis of differently substituted, optically pure cis,cis-C4,C4'-bis-beta-lactams If-i in good overall yields. C4,C4'-Bis-beta-lactams smoothly rearranged to fused trans,trans-bis-gamma-lactams 7 upon basic treatment (NaOMe/MeOH) in a totally stereoselective process. The presence of alkyl groups attached to the lactam nitrogen inhibits the rearrangement. Differently substituted (aryl and alkyl substituents in either rings) bicyclic p-lactam systems gave the selective opening of the ring with the aromatic substituent attached to the lactam nitrogen. Monocyclic 2-azetidinones 8 with an amino ester side chain at C4 are then obtained. The synthesis of trans,cis-C4,C4'-bis-beta-lactam Ij and trans,trans-C4,C4'-bis-beta-lactam 11 has also been effected in the racemic form. Compound Ij with a trans,cis stereochemistry rearranged to cis,trans-bis-gamma-lactam 7d in the presence of base while the trans,trans-bicycle 11 gave monocyclic 2-azetidinone 8c with an amino ester side chain. Finally, trans,trans-bis-gamma-lactam 11 can be synthesized in a single step from glyoxal diimine 3a employing an excess of lithium isovalerate. A reaction pathway to account for all the observed data is proposed.

  DOI：

  10.1021/jo960826c
• 作为产物：
  描述：

  (3R,4R)-cis-1-(p-anisyl)-3-(benzyloxy)-4-<(S)-2,2-dimethyl-1,3-dioxolan-4-yl>-2-azetidinone 在 sodium periodate 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 24.0h， 生成 (+)-(3R,4R)-1-(p-anisyl)-3-benzyloxy-4-formyl-2-azetidinone
  参考文献：
  名称：

  3,4-二取代的2-氮杂环丁酮向手性5,6-二氢-2-吡啶酮的轻松转化

  摘要：

  通过具有预先调整的取代基和立体化学的容易获得的3,4-二取代-2-氮杂环丁酮，通过2-氮杂环丁酮的还原性开环，有效地制备了手性5,6-二取代-5,6-二氢-2（1 H）-吡啶酮通过Z-选择性安装乙酸酯部分并再环化成2-吡啶酮。

  DOI：

  10.1016/s0040-4039(01)00470-1

文献信息

• Useful Dual Diels–Alder Behavior of 2-Azetidinone-Tethered Aryl Imines as Azadienophiles or Azadienes: A -Lactam-Based Stereocontrolled Access to Optically Pure Highly Functionalized Indolizidine Systems
  作者：Benito Alcaide、Pedro Almendros、Jose M. Alonso、Moustafa F. Aly

  DOI：10.1002/chem.200304712

  日期：2003.7.21

  diene in the presence of different Lewis acids. The effect of the amount of catalyst on the conversion rate as well as on the product ratio has been studied. Under standard reaction conditions, indium(III) chloride and zinc(II) iodide provided the best yields, and indium(III) triflate the highest diastereoselectivity in the Lewis acid promoted aza-Diels-Alder cycloaddition. Treatment of the aforementioned

  已经发现衍生自4-氧杂氮杂环丁烷-2-甲醛的亚胺是通用的Diels-Alder试剂，因为它们表现出两种反应模式。在不同的路易斯酸存在下，2-氮杂环丁酮系链的亚胺与Danishefsky的二烯进行非对映选择性反应。已经研究了催化剂的量对转化率以及产物比率的影响。在标准反应条件下，氯化铟（III）和碘化锌（II）提供的收率最高，而三氟甲磺酸铟（IIIflate）在路易斯酸中促进的氮杂-狄尔斯-阿尔德环加成反应的非对映选择性最高。用环戊二烯，2,3-二甲基-1,3-丁二烯或3处理上述亚胺，4-二氢-2 H-吡喃导致由反电子需求缩合产生的环加合物，其中涉及β-内酰胺系的芳基亚胺作为杂二烯组分。另外，已经开发了从β-内酰胺制备吲哚并立定的第一种方法。该过程涉及伴随有环化作用的氮杂-Diels-Alder环加合物中β-内酰胺环的酰胺键裂解。当与对映体纯的底物进行反应时，发生完全手性转移。
• Dual Behavior of 2-Azetidinone-Tethered Arylimines as Azadienophiles or Azadienes. Application to the Asymmetric Synthesis of Indolizidine-Type Systems
  作者：Benito Alcaide、Pedro Almendros、Jose M. Alonso、Moustafa F. Aly、M. Rosario Torres

  DOI：10.1055/s-2001-17453

  日期：——

  The first methodology to prepare indolizidine systems directly from β-lactams has been developed. This process involves the amide bond cleavage of the β-lactam ring in the aza Diels-Alder cycloadducts with concomitant cyclization. Indolizidinone precursors arise from normal, as well as inverse electron-demand condensation involving the C=N moiety of 2-azetidinone-tethered imines as the dienophile or the heterodiene contributor.

  已经开发出将β-内酯系统直接转化为吲哚啉体系的首个方法。这一过程涉及到在氮杂Diels-Alder环加成物中对β-内酯环的酰胺键裂解，同时伴随环化反应。吲哚啉酮前体的形成源自正常以及逆电子需求的缩合反应，其中2-噁烷酮连接的亚胺的C=N部分作为亲二烯或异二烯的贡献者。
• Base-Promoted Isomerization of <i>cis</i>-4-Formyl-2-azetidinones:  Chemoselective <i>C</i>4-Epimerization vs Rearrangement to Cyclic Enaminones
  作者：Benito Alcaide、Moustafa F. Aly、Carolina Rodríguez、Alberto Rodríguez-Vicente

  DOI：10.1021/jo991984h

  日期：2000.6.1

  N-(p-methoxyphenyl)-beta-lactams can be used, and (ii) transformation is less compatible with heteroatomic substituents bonded to the C3 position of the 2-azetidinone ring. A highly general solution to these problems relies on the use of sodium carbonate as the isomerization reagent in different solvents. We also describe a novel base-promoted rearrangement of the beta-lactam ring to cyclic enaminones 6

  描述了两种简单，有效和互补的方法，用于顺式-4-甲酰基-2-氮杂环丁烷酮1-3的区域特异性C4表异构化。第一种方法是在苄基三丁基溴化铵（3-4 mol％）作为相转移催化剂的情况下，在室温下于苯的非均相介质中使用40％的二甲胺水溶液作为试剂。该转化耐受2-氮杂环丁酮环的C 3上的烷基，烯基，炔基，芳基和烷氧基取代基。然而，这种异构化的局限性如下：（i）仅可使用N-（对甲氧基苯基）-β-内酰胺，并且（ii）转化与键合于2-氮杂环丁酮C3位的杂原子取代基的相容性较低。环。对于这些问题的高度通用的解决方案取决于在不同溶剂中使用碳酸钠作为异构化试剂。
• Synthesis and Biological Evaluation of C-3'-Modified Analogs of 9(R)-Dihydrotaxol
  作者：Leping Li、Sheela A. Thomas、Larry L. Klein、Clinton M. Yeung、Clarence J. Maring、David J. Grampovnik、Paul A. Lartey、Jacob J. Plattner

  DOI：10.1021/jm00043a005

  日期：1994.8

  Taxol (1) is considered a most exciting new drug in cancer chemotherapy. The promising antitumor activity of 9(R)-dihydrotaxol (3) encouraged us to further explore the structure-activity relationship of this new member of the taxane family. Studies indicated that the C-13 side chain of taxol is indispensable for antitumor activity and that the natural substitution pattern of a 2'(R)-hydroxy and a 3'(S)-acylamino

  紫杉醇（1）被认为是癌症化疗中最令人兴奋的新药。9（R）-二氢紫杉醇（3）的有希望的抗肿瘤活性鼓励我们进一步探索紫杉烷家族这个新成员的结构-活性关系。研究表明，紫杉醇的C-13侧链对于抗肿瘤活性是必不可少的，并且2'（R）-羟基和3'（S）-酰氨基的天然取代方式可能是最佳的。然而，关于3'-苯环对活性的影响了解的很少。描述了在C-3'位置修饰的3的类似物的合成和生物学评估。这项研究表明3'-苯环不是活性所必需的，并鉴定了几种在体外和体内活性均与紫杉醇相同或更高的化合物。
• Highly stereoselective synthesis of α-hydroxy β-amino acids through β-lactams: application to the synthesis of the taxol and bestatin side chains and related systems.
  作者：Claudio Palomo、Ana Arrieta、Fernando P. Cossío、Jesus M. Aizpurua、Antonia Mielgo、Natalia Aurrekoetxea

  DOI：10.1016/s0040-4039(00)97083-7

  日期：1990.1

  Formation of α-hydroxy β-lactams, followed chemical elaboration at C4 and further βlactam cleavage afforded functionalised α-hydroxy β-amino acids or their derivatives in a highly stereoselective manner.

  形成α-羟基β-内酰胺，随后在C 4进行化学精制并进一步裂解β-内酰胺，以高度立体选择性的方式得到官能化的α-羟基β-氨基酸或其衍生物。