5-O-methyl-2,4-O-(1-methylethylidene)-L-glucuronic acid γ-lactone | 270902-66-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-O-methyl-2,4-O-(1-methylethylidene)-L-glucuronic acid γ-lactone
• 英文别名: (4S,4aR,7R,7aR)-7-methoxy-2,2-dimethyl-6-oxotetrahydro-4H-furo[3,2-d][1,3]dioxine-4-carbaldehyde；(4S,4aR,7R,7aR)-7-methoxy-2,2-dimethyl-6-oxo-4,4a,7,7a-tetrahydrofuro[3,2-d][1,3]dioxine-4-carbaldehyde
• CAS: 270902-66-4
• 化学式: C₁₀H₁₄O₆
• 分子量: 230.218
• InChiKey: VVXUKAQBMLNZKQ-ULAWRXDQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-O-methyl-2,4-O-(1-methylethylidene)-L-glucuronic acid γ-lactone 在 chromium dichloride 、 四丁基氟化铵 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 4.5h， 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：

  葡庚糖酸内酯 在 sodium periodate 、 水 、 碘 、 silver(l) oxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 溶剂黄146 为溶剂， 反应 18.67h， 生成 5-O-methyl-2,4-O-(1-methylethylidene)-L-glucuronic acid γ-lactone
  参考文献：
  名称：

  苯甲酰胺B和E的总合成。

  摘要：

  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。

  DOI：

  10.1021/jo0017133

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。
• A Concise Synthesis of Bengamide E and Analogues via E-Selective Cross-Metathesis Olefination
  作者：Hamid Dhimane、Safiul Alam

  DOI：10.1055/s-0030-1259015

  日期：2010.12

  A modular, eight-step synthesis of bengamide E and six analogues from a common chiral pool has been developed. The key step in this approach is a cross-metathesis coupling of various commercial terminal olefins and a common alkene bearing the required stereogenic centers of bengamides lateral chain, which was easily derived from α-D-glucoheptonic-γ-lactone. Complete E-selectivity, and up to 92% yield

  已经开发了一种模块化的八步合成苯甲酰胺 E 和来自共同手性池的六种类似物。这种方法的关键步骤是将各种商业末端烯烃和带有所需的苯甲酰胺侧链立体中心的普通烯烃进行交叉复分解偶联，这很容易从α-D-葡萄糖庚酸-γ-内酯衍生而来。这一关键的交叉复分解步骤实现了完全的 E 选择性和高达 92% 的产率。
• Design, Synthesis and Biological Evaluation of Bengamide Analogues as <scp>ClpP</scp> Activators
  作者：Xue‐Qing Kong、Bing‐Yan Wei、Chen‐Xi Yu、Xiang‐Na Guan、Wei‐Ping Ma、Gang Liu、Cai‐Guang Yang、Fa‐Jun Nan

  DOI：10.1002/cjoc.202000133

  日期：2020.10

  conducted a screening on our library of bengamide‐like ring‐opened analogues and found that L472‐2 possesses a low minimum inhibitory concentration (MIC) against S.aureus and shows no activity for ClpP activation in vitro, but it displayed reduced antibacterial activity against S. aureus with clpP deletion. In order to obtain bengamide analogues that activate ClpP in vitro as well as possess antibacterial

  为了对抗具有多重耐药性的革兰氏阳性细菌，迫切需要新的抗菌药物，尤其是具有新作用机制的抗菌药物。与典型的常规抗生素不同，细菌ClpP的小分子激活剂代表了一类新的抗生素。尚未开发用于临床试验的ClpP激活剂。在此，我们在我们的bengamide状的开环类似物文库进行了筛选，结果发现L472-2具有针对较低的最低抑制浓度（MIC）的金黄色葡萄球菌和示出了用于激活CLPP没有活性在体外，但它显示的缩小对抗菌活性金黄色葡萄球菌与CLPP删除。为了获得可在体外激活ClpP并具有抗菌活性的苯甲酰胺类似物，我们从L472-2开始进行进一步的结构修饰。化合物37在体外仍具有抗菌活性和对ClpP蛋白的激活作用，可作为ClpP激活剂的新型化学支架，值得进一步研究。
• 2-ALKOXY-3,4,5-TRIHYDROXY-ALKYLAMIDES, PREPARATION THEREOF, COMPOSITIONS CONTAINING THEM AND USE THEREOF
  申请人：ZHANG Jidong

  公开号：US20070244087A1

  公开（公告）日：2007-10-18

  The invention relates particularly to 2-alkoxy-3,4,5-trihydroxy-alkylamides, preparation thereof, compositions containing them and use thereof as a medicament, particularly as anti-cancer agents.

  该发明特别涉及2-烷氧基-3,4,5-三羟基-烷酰胺，其制备方法，含有它们的组合物以及将其用作药物，特别是作为抗癌剂的用途。
• ALPHA-AMINO-N-SUBSTITUTED AMIDES, PHARMACEUTICAL COMPOSITION CONTAINING THEM AND USES THEREOF
  申请人：SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES

  公开号：EP2233467A1

  公开（公告）日：2010-09-29

  The present invention relates to filed of pharmaceutical chemistry. Disclosed are a series of α-amino-N-substituted amide compounds having a structure of the following formula, the pharmaceutically acceptable salts thereof, and the pharmaceutical composition comprising the same. The α-amino-N-substituted amide compounds or the pharmaceutically acceptable salts thereof according to the present invention have anti-tumor and/or anti-cancer activities in vivo and in vitro, can effectively depress the growth of various tumor cells and/or cancer cells, and thus can be used in preparing drugs for treating tumors and/or cancers.

  本发明涉及药物化学领域。本发明公开了一系列具有下式结构的α-氨基-N-取代酰胺化合物、其药学上可接受的盐，以及由其组成的药物组合物。根据本发明的α-氨基-N-取代酰胺化合物或其药学上可接受的盐在体内和体外具有抗肿瘤和/或抗癌活性，能有效抑制各种肿瘤细胞和/或癌细胞的生长，因此可用于制备治疗肿瘤和/或癌症的药物。