(3S,6R)-3-(tert-butyloxycarbonyl)aminohexahydro-6-hydroxy-2H-azepin-2-one | 270902-68-6

• 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: (3S,6R)-3-(tert-butyloxycarbonyl)aminohexahydro-6-hydroxy-2H-azepin-2-one
• 英文别名: (3S,6R)-3-[(tert-butoxycarbonyl)amino]-6-hydroxycaprolactam；(3S, 6R)-3-(tert-butoxycarbonyl)aminohexahydro-6-hydroxy-2H-azepin-2-one；(2S,5R)-2-[(tert-butoxycarbonyl)amino]-5-hydroxycaprolactam；(3S,6R)-3-(tert-butoxycarbonyl)aminohexahydro-6-hydroxy-2H-azepin-2-one；tert-butyl N-[(3S,6R)-6-hydroxy-2-oxoazepan-3-yl]carbamate
• CAS: 270902-68-6
• 化学式: C₁₁H₂₀N₂O₄
• 分子量: 244.291
• InChiKey: SVIMTGHKHMNLAM-SFYZADRCSA-N

物化性质

• 沸点：
  471.5±45.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3S,6R)-3-(tert-butyloxycarbonyl)aminohexahydro-6-hydroxy-2H-azepin-2-one 在 咪唑 、 碘代三甲硅烷 、 四丁基氟化铵 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 3.75h， 生成 (2R,3R,4S,5R,6E)-3,5-(methylethylidene)-3,4,5-trihydroxy-2-methoxy-8,8-dimethyl-N-[(3S,6R)-hexahydro-2-oxo-6-hydroxy-2H-azepin-3-yl]non-6-enamide
  参考文献：
  名称：

  Synthesis and Antitumor Activity of Ester-Modified Analogues of Bengamide B

  摘要：

  Bengamide B, a novel sponge-derived marine natural product with broad spectrum antitumor activity, was not suitable for further preclinical development because of its difficult synthesis and very poor water solubility. Bengamide B produced a 31% T/C at its solubility-limited maximum intravenous dose of 33 micromol/kg in MDA-MB-435 breast carcinoma implanted subcutaneously as a xenograft in nude mice. Compound 8a, a bengamide B analogue with three structural changes (t-Bu alkene substituent, unsubstituted lactam nitrogen, and inverted lactam 5'-myristoyloxy group), was as potent as bengamide B in vitro and more efficacious than bengamide B in vivo. A series of ester-modified analogues based on 8a were synthesized and tested in vitro and in vivo (MDA-MB-435). The cyclohexyl- and phenethyl-substituted esters, 8c and 8g, respectively, had in vitro and in vivo activities similar to that of 8a and enhanced water solubility (ca. 1 mg/mL). Consequently, 8c and 8g were tested in the MDA-MB-435 xenograft model at 100 micromol/kg and produced 29% and 57% tumor regression, respectively.

  DOI：

  10.1021/jm010188c
• 作为产物：
  描述：

  (2S)-2-(双(叔丁氧羰基)氨基)-5-氧代戊酸甲酯 在 (R)-lanthanum-lithium-BINOL ((R)-LLB) lanthanum(III) isopropoxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 48.0h， 生成 (3S,6R)-3-(tert-butyloxycarbonyl)aminohexahydro-6-hydroxy-2H-azepin-2-one
  参考文献：
  名称：

  由L-谷氨酸立体选择性合成2-氨基-5-羟基己内酰胺

  摘要：

  （2 S，5 S）-和（2 S，5 R）-2-氨基-5-羟基己内酰胺的五步立体选择性合成已经通过1-谷氨酸1与硝基甲烷的醛醇缩合反应实现。

  DOI：

  10.1016/s0040-4039(00)02307-8

文献信息

• Total Syntheses of Bengamides B and E
  作者：Frederick R. Kinder,、Sompong Wattanasin、Richard W. Versace、Kenneth W. Bair、John Bontempo、Michael A. Green、Yansong J. Lu、H. Rao Marepalli、Penny E. Phillips、Didier Roche、Long D. Tran、RunMing Wang、Liladhar Waykole、David D. Xu、Sonya Zabludoff

  DOI：10.1021/jo0017133

  日期：2001.3.1

  Total syntheses of the cytotoxic marine natural products bengamides B and E are described. Both bengamides are prepared via amide coupling of a protected polyhydroxylated lactone intermediate 9 with a suitably substituted aminocaprolactam intermediate. Lactone 9 is prepared in five steps from commercially available alpha-D-glucoheptonic gamma-lactone. The key reactions are a selective deprotection

  描述了细胞毒性海洋天然产物苯甲酰胺B和E的总合成。通过保护的多羟基化内酯中间体9与适当取代的氨基己内酰胺中间体的酰胺偶联制备两种苯甲酰胺。内酯9是由市售的α-D-葡庚酮γ-内酯分五个步骤制备的。关键反应是在1,3-丙酮化物的存在下1,2-丙酮化物的选择性脱保护以及使用宝石重铬试剂对不稳定醛的（E）选择性烯化。苯甲酰胺B内酰胺中间体10由市售的（5R）-5-羟基-L-赖氨酸（12）以七个步骤制备。使用Mitsunobu反应确定在γ-OH内酰胺位置上的所需S构型。
• Certain substituted caprolactam carbonates and ethers, pharmaceutical compositions containing them and their use in treating tumors
  申请人：Novartis AG

  公开号：US06413954B1

  公开（公告）日：2002-07-02

  The present invention relates to certain substituted caprolactam carbonate and ether compounds, pharmaceutical compositions containing said compounds, the use of said compounds in treating tumors and to a process for making said compounds.

  本发明涉及某些取代的己内酰胺碳酸酯和醚化合物，含有该化合物的药物组合物，利用该化合物治疗肿瘤的方法以及制备该化合物的过程。
• Synthesis of 2-Amino-5-hydroxycaprolactam Derivatives Mediated by E-Selective Olefination and Asymmetric Oxidation of the Enol Ether
  作者：Guo-Chun Zhou、Hong Li、Yingxue Liu、Qijun Liu、Wenhui Hu

  DOI：10.1055/s-0030-1258275

  日期：2010.12

  The asymmetric synthesis of 2-amino-5-hydroxycaprolactam derivatives is essential for exploring the antitumor properties of ester-bearing bengamides. In this study, chiral caprolactam isomers were achieved on the basis of highly E-selective Wittig olefination, asymmetric oxidations of the E-enol ethers, reductive amination of the aldehyde derivatives, cyclization of the 5-hydroxy­lysine analogues or/and

  2-氨基-5-羟基己内酰胺衍生物的不对称合成对于探索含酯的苯甲酰胺的抗肿瘤特性至关重要。在这项研究中，手性己内酰胺异构体是在高度E-选择性Wittig烯化，E-烯醇醚的不对称氧化，醛衍生物的还原胺化，5-羟基赖氨酸类似物的环化或/和脱保护的基础上获得的。 己内酰胺- ë -选择性烯-不对称氧化-烯醇醚-还原性胺化
• An Expedient Synthesis of LAF389, a Bengamide B Analogue
  作者：David D. Xu、Liladhar Waykole、John V. Calienni、Lech Ciszewski、George T. Lee、Wenming Liu、Joanna Szewczyk、Kevin Vargas、Kapa Prasad、Oljan Repič、Thomas J. Blacklock

  DOI：10.1021/op0341162

  日期：2003.11.1

  convergent, safe synthesis of LAF389 (9), an anti-cancer agent analogous to bengamide B, is described. Starting from α-d-glucoheptonic (d-glycero-d-gulo-heptonic acid) γ-lactone (10), the lactone 15 was constructed in five steps. Major improvements were made in the preparation of the aldehyde precursor 14 and subsequent olefination to yield 15 via a modified Julia protocol. This olefination was significantly

  描述了 LAF389 (9) 的优化、收敛、安全合成，这是一种类似于苯甲酰胺 B 的抗癌剂。从α-d-葡庚糖（d-甘油-d-古洛庚酸）γ-内酯（10）开始，分五步构建内酯15。在醛前体 14 的制备和随后的烯烃化以通过改进的 Julia 方案产生 15 方面进行了重大改进。通过使用 TMSCl 作为添加剂，这种烯烃化得到了显着改善。药物物质的第二个片段，ε-己内酰胺 7，是从 (5R)-5-羟基-l-赖氨酸 (1) 中通过两次一锅法获得的。最后，使用 2-乙基己酸钠 (Na-EH) 用 7 打开 15，得到 8，其脱保护得到 LAF389。
• [EN] SUBSTITUTED LACTAMS AND THEIR USE AS ANTI-CANCER AGENTS<br/>[FR] LACTAMES SUBSTITUES ET UTILISATION DE CEUX-CI EN TANT QU'AGENTS ANTI-CANCEREUX
  申请人：NOVARTIS AG

  公开号：WO2005014574A1

  公开（公告）日：2005-02-17

  This invention relates to certain substituted lactam compounds of the formula (I), particularly caprolactam compounds, which are useful for the treatment of cancer.

  本发明涉及公式（I）的某些取代内酰胺化合物，特别是己内酰胺化合物，其用于治疗癌症。