methyl (3R,4R,5S,6R)-3,4-O-cyclohexylidene-5,6-epoxy-3,4-dihydroxy-1-cyclohexene-1-carboxylate | 133398-70-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl (3R,4R,5S,6R)-3,4-O-cyclohexylidene-5,6-epoxy-3,4-dihydroxy-1-cyclohexene-1-carboxylate
• 英文别名: methyl (3a'R,5a'R,6a'R,6b'R)-3a',5a',6a',6b'-tetrahydrospiro[cyclohexane-1,2'-oxireno[2',3':3,4]benzo[1,2-d][1,3]dioxole]-5'-carboxylate；methyl (3aR,5aR,6aR,6bR)-spiro[3a,5a,6a,6b-tetrahydrooxireno[2,3-g][1,3]benzodioxole-2,1'-cyclohexane]-5-carboxylate
• CAS: 133398-70-6
• 化学式: C₁₄H₁₈O₅
• 分子量: 266.294
• InChiKey: AACNZPMBVVZNTR-DDHJBXDOSA-N

物化性质

• 沸点：
  389.6±42.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  57.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl (3R,4R,5S,6R)-3,4-O-cyclohexylidene-5,6-epoxy-3,4-dihydroxy-1-cyclohexene-1-carboxylate 在 盐酸 、 Methyl (3S,4R,5R)-3,4-O-cyclohexylidene-3,4-epi-shikimate 作用下， 以 乙醚 为溶剂， 反应 24.0h， 以6%的产率得到methyl (3R,4R,5S,6S)-6-chloro-3,4-O-cyclohexylidene-3,4,5-trihydroxy-1-cyclohexene-1-carboxylate
  参考文献：
  名称：

  海洋天然产物（-）-Pericosine E的合成

  摘要：

  已实现（-）-pericosine E（6）的首次合成，E-pericosine E（6）是最初从海兔Aplysia kurodai分离得到的Periconia byssoides OUPS-N133的代谢物。为关键中间体的合成，有效和区域选择性的合成方法的抗与顺式环氧化物9和10，分别使用开发抗二烯-epoxidation 12与TFDO和的bromohydrination 12与NBS在CH 3 CN / H 2 O（ 2：3）。此外，合成6的特定旋光度比较天然6阐明，天然优选的Percosine E对映异构体具有与由氯代醇（-）- 8和抗环氧（+）- 9合成的（-）- 6相同的绝对构型。

  DOI：

  10.1021/ol501631r
• 作为产物：
  描述：

  methyl shikimate 在 吡啶 、 4-二甲氨基吡啶 、 oxone 、 camphor-10-sulfonic acid 、 cesium acetate 、 碳酸氢钠 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 methyl (3R,4R,5S,6R)-3,4-O-cyclohexylidene-5,6-epoxy-3,4-dihydroxy-1-cyclohexene-1-carboxylate
  参考文献：
  名称：

  An Electrophilic Natural Product Provides a Safe and Robust Odor Neutralization Approach To Counteract Malodorous Organosulfur Metabolites Encountered in Skunk Spray

  摘要：

  The anal secretions of skunks comprise several types of malodorous organosulfur compounds. The pungent metabolites are used defensively by skunks to repel threats posed by predators, and in many parts of the world, those perceived threats include humans and their pets. The extremely low thresholds for detection of the organosulfur metabolites make efforts to "de-skunk" people, animals, and clothing a process fraught with many challenges. The fungal-derived metabolite pericosine A (4) is a promiscuous yet stabile electrophilic compound that we propose is used by some fungi as a novel form of chemical defense. Our investigations have indicated that pericosine A readily reacts with skunk-spray secretions to transform them into odorless products. Mechanistic and computational studies suggested that pericosine A and its synthetic analogues react via S_N2'-type mechanisms with thiols and thioacetates under aqueous conditions to generate stable thioethers. Testing revealed that pericosine A did not cause skin or eye irritation and was highly effective at deodorizing skunk anal gland secretions when formulated to include adjunctive cosmetic ingredients.

  DOI：

  10.1021/acs.jnatprod.9b00415

文献信息

• Synthesis of (−)-pericosine B, the antipode of the cytotoxic marine natural product
  作者：Yoshihide Usami、Kentaro Suzuki、Koji Mizuki、Hayato Ichikawa、Masao Arimoto

  DOI：10.1039/b813072h

  日期：——

  The stereoselective synthesis of (−)-pericosine B, which is the antipode of the cytotoxic metabolite of the fungus Periconia byssoides OUPS-N133 separated from the sea hare, was accomplished in 9 steps in 12% total yield from (−)-quinic acid, together with the synthesis of its epimer. Every crucial step of this total synthesis, including ring opening of a β-epoxide and NaBH4reduction of an unstable

  与海兔分离的真菌（Periconia byssoides OUPS-N133）的细胞毒性代谢产物的对映体（-）-pericosine B的立体选择性合成以9步完成，从（-）-奎宁酸的总收率为12％ ，连同其差向异构体的合成。整个合成过程中的每个关键步骤，包括β-环氧化物的开环和不稳定的β，γ-不饱和烯酮的NaBH 4还原，都具有出色的立体选择性。
• Syntheses and Glycosidase Inhibitory Activities, and in Silico Docking Studies of Pericosine E Analogs Methoxy-Substituted at C6
  作者：Yoshihide Usami、Megumi Higuchi、Koji Mizuki、Mizuki Yamamoto、Mao Kanki、Chika Nakasone、Yuya Sugimoto、Makio Shibano、Yoshihiro Uesawa、Junko Nagai、Hiroki Yoneyama、Shinya Harusawa

  DOI：10.3390/md18040221

  日期：——

  Inspired by the significant -glucosidase inhibitory activities of (+)- and (-)-pericosine E, we herein designed and synthesized 16 analogs of these marine natural products bearing a methoxy group instead of a chlorine atom at C6. Four of these compounds exhibited moderate -glucosidase inhibitory activities, which were weaker than those of the corresponding chlorine-containing species. The four compounds

  受（+）-和（-）-pericosine E的α-葡萄糖苷酶显着抑制活性的启发，我们在此设计和合成了这些海洋天然产物的16个类似物，这些类似物在C6处带有甲氧基而不是氯原子。这些化合物中的四种表现出中等的β-葡萄糖苷酶抑制活性，比相应的含氯物质弱。可以通过利用（-）-pericosine B部分进行偶联反应来制备这四种化合物。另外的计算机对接模拟表明，C6-甲氧基化类似物的活性降低的原因可能是甲氧基与β-葡糖苷酶活性位点周围的氨基酸残基之间没有氢键。
• Synthesis of Natural O-Linked Carba-Disaccharides, (+)- and (−)-Pericosine E, and Their Analogues as α-Glucosidase Inhibitors
  作者：Yoshihide Usami、Koji Mizuki、Rikiya Kawahata、Makio Shibano、Atsuko Sekine、Hiroki Yoneyama、Shinya Harusawa

  DOI：10.3390/md15010022

  日期：——

  Pericosine E (6), a metabolite of Periconia byssoides OUPS-N133 was originally isolated from the sea hare Aplysia kurodai, which exists as an enantiomeric mixture in nature. The enantiospecific syntheses of both enantiomers of Periconia byssoides OUPS-N133 has been achieved, along with six stereoisomers, using a common simple synthetic strategy. For these efficient syntheses, highly regio- and steroselective

  Pericosine E（6）是Periconia byssoides OUPS-N133的代谢产物，最初是从海兔Aplysia kurodai中分离出来的，该菌在自然界中以对映体混合物的形式存在。使用普通的简单合成策略，已实现了Periconia byssoides OUPS-N133的两个对映体的对映体特异性合成，以及六个立体异构体。对于这些有效的合成，采用了高度区域选择性和立体选择性的方法来制备溴代醇和抗环氧中间体。为了获得独特的O-连接的二糖结构，使用催化的BF 3·Et 2 O实现了氯醇作为供体和抗环氧化物作为受体的偶联。大多数合成的化合物对来自酵母的α-糖苷酶表现出选择性显着的抑制活性。
• The synthesis of 6-substituted shikimic acids
  作者：James K. Sutherland、Roger C. Whitehead、Gareth M. Davies

  DOI：10.1039/c39930000464

  日期：——

  6-Hydroxy-, 6-amino- and 6-mercapto-shikimic acids have been synthesised from quinic acid and improved methods developed for the synthesis of the 6-fluoroshikimic acids.

  6-羟基-、6-氨基-和6-巯基-莽草酸已由奎尼酸合成，并开发了用于合成6-氟莽草酸的改进方法。
• Determination of the absolute configuration of the cytotoxic natural product pericosine D
  作者：Yoshihide Usami、Koji Mizuki、Hayato Ichikawa、Masao Arimoto

  DOI：10.1016/j.tetasy.2008.06.008

  日期：2008.6

  The synthesis of two diastereomers of pericosine A from (-)-quinic acid was achieved, thus enabling the confirmation of the relative configuration and elucidation of the absolute stereochemistry of cytotoxic natural product pericosine D assigned as methyl (3R,4R,5S,6R)-6-chloro-3,4,5-trihydroxy-1-cyclohexene-1-carboxylate. (C) 2008 Elsevier Ltd. All rights reserved.