3-amino-4,4-dimethoxy-5,6-epoxycyclohex-2-en-1-on

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-amino-4,4-dimethoxy-5,6-epoxycyclohex-2-en-1-on
• 英文别名: 3-amino-4,4-dimethoxy-5,6-epoxycyclohex-2-en-1-one；(2RS,3SR)-5-amino-2,3-epoxy-4,4-dimethoxycyclohex-5-en-1-one；(1S,6R)-4-amino-5,5-dimethoxy-7-oxabicyclo[4.1.0]hept-3-en-2-one
• 化学式: C₈H₁₁NO₄
• 分子量: 185.18
• InChiKey: IVTVOSRODLZJCS-RNFRBKRXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  74.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-amino-4,4-dimethoxy-5,6-epoxycyclohex-2-en-1-on 在 三乙基硼氢化锂 、 lithium tert-butoxide 作用下， 以 四氢呋喃 为溶剂， 生成 (E)-(S)-2,4-Dimethyl-oct-2-enoic acid ((1R,6R)-5-hydroxy-2,2-dimethoxy-7-oxa-bicyclo[4.1.0]hept-3-en-3-yl)-amide
  参考文献：
  名称：

  Grove, J. J. Cronje; Wei, Xudong; Taylor, Richard J. K., Chemical Communications, 1999, # 5, p. 421 - 422

  摘要：

  DOI：
• 作为产物：
  描述：

  (2S,3R)-5-tert-butoxycarbonylamino-2,3-epoxy-4,4-dimethoxycyclohex-5-en-1-one 在 苯甲醚 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以98%的产率得到3-amino-4,4-dimethoxy-5,6-epoxycyclohex-2-en-1-on
  参考文献：
  名称：

  Manumycin A，B和C抗生素的合成方法：（+）-Manumycin A的首次全合成

  摘要：

  报道了Manumycin A作为其（+）-对映异构体的第一个全合成。该合成路线具有不对称环氧化（基于Wynberg手性相转移方法）的特点，用于制备关键的环氧喹啉核，并进一步证明了Stille反应在构建Manumycin下部侧链方面的效用。Manumycin A的这种合成纠正了原来的立体化学分配，并确认了顺式-羟基环氧化物的排列。还描述了通过Manumycins AC的氧化降解获得的醌的第一合成。

  DOI：

  10.1016/s0040-4020(98)00879-5

文献信息

• Synthesis and Structure–Activity Relationship of Dehydroxymethylepoxyquinomicin Analogues as Inhibitors of NF-κB Functions
  作者：Chanya Chaicharoenpong、Kuniki Kato、Kazuo Umezawa

  DOI：10.1016/s0968-0896(02)00315-2

  日期：2002.12

  omicin (DHMEQ) inhibited NF-kappaB activation and showed anti-inflammatory activity in vivo. Here we designed and synthesized analogues of DHMEQ and tested their biological activity as NF-kappaB inhibitors in human T cell leukemia Jurkat cells. The hydroxyl group at the 2-position of the benzamide moiety was found to be essential for the inhibitory activity. But etherification of this group did not

  我们先前发现脱羟甲基环氧喹诺酮（DHMEQ）抑制NF-κB活化并在体内表现出抗炎活性。在这里，我们设计并合成了DHMEQ的类似物，并测试了它们在人T细胞白血病Jurkat细胞中作为NF-κB抑制剂的生物学活性。发现苯甲酰胺部分的2-位上的羟基对于抑制活性是必需的。但是该组的醚化并未完全降低活性。因此，对于进一步的机理研究，在2-位的羟基对于与接头和生物素部分的延伸可能是有用的。
• Chemoenzymatic synthesis of (2R,3R,4R)-dehydroxymethylepoxyquinomicin (DHMEQ), a new activator of antioxidant transcription factor Nrf2
  作者：Yukihiro Niitsu、Masatoshi Hakamata、Yuko Goto、Toshinori Higashi、Mitsuru Shoji、Takeshi Sugai、Kazuo Umezawa

  DOI：10.1039/c1ob05205e

  日期：——

  >500) to give (1S,2S,3S)-2a in an enantiomerically pure state. Several chemical steps of transformation from the enzyme reaction product gave (2R,3R,4R)-DHMEQ (1a) without any loss of stereochemical purity. Moreover, we newly found that (2R,3R,4R)-DHMEQ activated Nrf2, which is a transcription factor that induces the expression of multiple antioxidant enzymes. It activated Nrf2 in a promoter reporter assay

  Dehydroxymethylepoxyquinomicnomicin（DHMEQ，1a）是NF-κB的特异有效抑制剂，目前正被开发为抗炎和抗癌药。尽管以前通过脂肪酶催化的对映选择性拆分只能从外消旋物中获得（2S，3S，4S）形式，但在本研究中，通过以下方法建立了生产（2R，3R，4R）形式的新途径使用化学酶学方法。（1R *，2R *，3R *）-2,3-环氧-5-N-[（2-羟基苯甲酰基）氨基] -4,4-二甲氧基环己基-5-烯-1-醇（2a）在两者上均被己酰化仲和酚羟基，并进行伯克霍尔德酒原脂酶的水解。反应以高度对映选择性的方式进行（E> 500），得到对映体纯态的（1S，2S，3S）-2a。从酶反应产物转化的几个化学步骤得到了（2R，3R，4R）-DHMEQ（1a），而没有任何立体化学纯度的损失。此外，我们新发现（2R，3R，4R）-DHMEQ激活了Nrf2，Nrf2是诱导多种抗氧
• Total Synthesis of (±)-Nisamycin
  作者：Peter Wipf、Philip D. G. Coish

  DOI：10.1021/jo990413m

  日期：1999.7.1

  We have developed a highly convergent synthesis of the manumycin-type m-C7N-antibiotic nisamycin that is applicable to other members of this family of antibiotics. The synthesis features a three-step sequence to the epoxyquinol core that serves as a scaffold for the attachment of the polyene side chains. The eastern polyene side chain was constructed via a novel organozirconocene-mediated synthesis. Zirconocene methodology was also applied to the synthesis of the polyene side chains of asukamycin. The southern side chain of nisamycin was introduced via a Stille reaction that employed a vinyl bromo ketone, derived from an acid-sensitive bromo ketal. Pd-mediated coupling of the vinyl bromide with a stannyl TIPS ester gave TIPS-protected nisamycin that was readily converted to the natural product.
• Chemoenzymatic synthesis of (2S,3S,4S)-form, the physiologically active stereoisomer of dehydroxymethylepoxyquinomicin (DHMEQ), a potent inhibitor on NF-κB
  作者：Manabu Hamada、Yukihiro Niitsu、Chihiro Hiraoka、Ikuko Kozawa、Toshinori Higashi、Mitsuru Shoji、Kazuo Umezawa、Takeshi Sugai

  DOI：10.1016/j.tet.2010.07.013

  日期：2010.8

  A new route for (2S,3S,4S)-form, the physiologically active stereoisomer of dehydroxymethylepoxyquinomicin (DHMEQ), a potent NF-kappa B inhibitor, was established by chemoenzymatic approach. Elaboration on the asymmetric epoxidation of a p-benzoquinone monoketal with benzylcinchonidinium tert-butylhydroperoxide yielded an epoxyenone, in 79.8% ee and 57% yield in reproducible manner. By way of the transformation of this key intermediate to enantiomerically pure (2S,35,4S)-DHMEQ the contaminating undesired enantiomer could be effectively removed by applying Burkholderia cepacia lipase-catalyzed hydrolysis of diacylated precursor. The above integrated combination of chemical asymmetric synthesis and enzyme-catalyzed kinetic resolution enabled us to prepare active DHMEQ in a large-scale. (C) 2010 Elsevier Ltd. All rights reserved.
• Manumycin A:  Synthesis of the (+)-Enantiomer and Revision of Stereochemical Assignment
  作者：Lilian Alcaraz、Gregor Macdonald、Jacques P. Ragot、Norman Lewis、Richard J. K. Taylor

  DOI：10.1021/jo980340r

  日期：1998.5.1