(+)-9,10-syn-copalol | 142793-44-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (+)-9,10-syn-copalol
• 英文别名: syn-copalol；anticopalol；(E)-5-[(1R,4aS,8aS)-5,5,8a-trimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]-3-methylpent-2-en-1-ol
• CAS: 142793-44-0
• 化学式: C₂₀H₃₄O
• 分子量: 290.489
• InChiKey: NERNKRPBSOBEHC-HZEYQZKKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (+)-9,10-syn-copalol 在 manganese(IV) oxide 作用下， 以 正己烷 为溶剂， 反应 4.0h， 以90%的产率得到(E)-5-[(1R,4aS,8aS)-5,5,8a-trimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]-3-methylpent-2-enal
  参考文献：
  名称：

  Total synthesis of (+)-9,10-syn- and (+)-9,10-anti-copalol via epoxy trienylsilane cyclizations.

  摘要：

  Total syntheses of (+)-9,10-syn-copalol (5), the pyrophosphate ester of which is a likely intermediate in the biosynthesis of 9,10-syn diterpenes, and its 9,10-anti isomer 39 are reported. Lithiation of (-)-(6R)-6,7-epoxygeranyl p-tolylsulfone (-)-19 or (+/-)-19 followed by alkylation with (E,Z)- and (E,E)-8-bromo-9-(trimethylsilyl)geranyl benzyl ethers (15a and 15b) and selective reductive cleavage of the toluenesulfonyl and benzyl groups afforded (2E,6E,10E,14R)- and (2E,6Z,10E,14R)-14,15-epoxy-19-(trimethylsilyl)geranylgeraniols ((-)-24a and (+/-)-26a). Lewis acid treatment of the benzoate and/or acetates of (-)-24a and (+/-)-26a effected efficient but almost stereorandom bicyclizations to 9,10-syn- and 9,10-anti-labda-8(17),13(E)-diene-3-beta,15-diol esters (27a,b and 28a,b) which were converted to (+)-9,10-syn- and (+)-9,10-anti-copalol.

  DOI：

  10.1021/jo00043a014
• 作为产物：
  描述：

  在 sodium hydroxide 、 四丁基醋酸铵 、 儿萘酚硼烷 作用下， 以 甲醇 为溶剂， 反应 9.0h， 生成 (+)-9,10-syn-copalol
  参考文献：
  名称：

  Total synthesis of (+)-9,10-syn- and (+)-9,10-anti-copalol via epoxy trienylsilane cyclizations.

  摘要：

  Total syntheses of (+)-9,10-syn-copalol (5), the pyrophosphate ester of which is a likely intermediate in the biosynthesis of 9,10-syn diterpenes, and its 9,10-anti isomer 39 are reported. Lithiation of (-)-(6R)-6,7-epoxygeranyl p-tolylsulfone (-)-19 or (+/-)-19 followed by alkylation with (E,Z)- and (E,E)-8-bromo-9-(trimethylsilyl)geranyl benzyl ethers (15a and 15b) and selective reductive cleavage of the toluenesulfonyl and benzyl groups afforded (2E,6E,10E,14R)- and (2E,6Z,10E,14R)-14,15-epoxy-19-(trimethylsilyl)geranylgeraniols ((-)-24a and (+/-)-26a). Lewis acid treatment of the benzoate and/or acetates of (-)-24a and (+/-)-26a effected efficient but almost stereorandom bicyclizations to 9,10-syn- and 9,10-anti-labda-8(17),13(E)-diene-3-beta,15-diol esters (27a,b and 28a,b) which were converted to (+)-9,10-syn- and (+)-9,10-anti-copalol.

  DOI：

  10.1021/jo00043a014

文献信息

• Substrate specificity of Rv3378c, an enzyme from Mycobacterium tuberculosis, and the inhibitory activity of the bicyclic diterpenoids against macrophagephagocytosis
  作者：Tsutomu Hoshino、Chiaki Nakano、Takahiro Ootsuka、Yosuke Shinohara、Takashi Hara

  DOI：10.1039/c0ob00884b

  日期：——

  The Rv3378c gene product from Mycobacterium tuberculosis encodes a diterpene synthase to produce tuberculosinol (3), 13R-isotuberculosinol (4a), and 13S-isotuberculosinol (4b) from tuberculosinyl diphosphate (2). The product distribution ratios are 1 : 1 for 3 to 4 and 1 : 3 for 4a to 4b. The substrate specificity of the Rv3378c-encoded enzyme was examined. The 3 labdadienyl diphosphates, copalyl diphosphate (CDP) (7), ent-CDP (8), and syn-CDP (9), underwent the conversion reaction, with good yields (67–78%). Copalol (23) and manool (24) were produced from 7, ent-copalol (25) and ent-manool (26) from 8, and syn-copalol (27) and vitexifolin A (28) from 9. The ratio of 23 to 24 was 40 : 27, that of 25:26 was 22 : 50, and that of 27:28 was 16 : 62. Analysis on a GC-MS chromatograph equipped with a chiral column revealed that 24, 26, and 28 consisted of a mixture of 13R- (a) and 13S-stereoisomers (b) in the following ratio: ca. 1 : 1 for 24a to 24b, ca. 1 : 5 for 26a to 26b, and ca. 1 : 19 for 28a to 28b. The structures of these products indicate that the reactions of the 3 CDPs proceeded in the same fashion as that of 2. This is the first report on the enzymatic synthesis of natural diterpenes manool, ent-manool, and vitexifolin A. Both Rv3377c and Rv3378c genes are found in virulent Mycobacterium species, but not in avirulent species. We found that 3 and 4 inhibited the phagocytosis of opsonized zymosan particles by human macrophage-like cells. Interestingly, the inhibitory activity was synergistically increased by the coexistence of 3 and 4b. Other labdane-related diterpenes, 13–16 and 23–28, had little or no inhibitory activity. This synergistic inhibition by 3 and 4 may provide further advantage to the impairment of phagocyte function, which might contribute to pathogenicity of M. tuberculosis.

  结核分枝杆菌的 Rv3378c 基因产品编码一种二萜合成酶，可从结核苷二磷酸（2）中产生结核苷醇（3）、13R-异结核苷醇（4a）和 13S- 异结核苷醇（4b）。产物分布比为 1 ：3 和 4 的产物分布比为 1 : 1，4a 和 4b 的产物分布比为 1 ：4a 和 4b 的产物分布比分别为 1 : 1 和 1 : 3。对 Rv3378c 编码酶的底物特异性进行了研究。3 种拉巴二烯基二磷酸酯，即二磷酸 copalyl (CDP)（7）、二磷酸 ent-CDP（8）和二磷酸 syn-CDP（9）发生了转化反应，且收率良好（67-78%）。由 7 生成了 Copalol (23) 和 manool (24)，由 8 生成了 ent-copalol (25) 和 ent-manool (26)，由 9 生成了 syn-copalol (27) 和 vitexifolin A (28)：50，27:28 的比例为 16:62。在配有手性色谱柱的气相色谱-质谱仪上进行的分析表明，24、26 和 28 由 13R 立体异构体 (a) 和 13S 立体异构体 (b) 的混合物组成，比例如下：24a 和 24b 约为 1 ：24a 至 24b 约为 1 : 1，26a 至 26b 约为 1 ：26a 至 26b 约为 1 : 5，28a 至 28b 约为 1 ：28a 至 28b 的比例约为 1 : 19。这些产物的结构表明，3 个 CDPs 的反应过程与 2 的反应过程相同。 这是首次报道天然二萜马诺醇、ent-马诺醇和荆芥苷 A 的酶法合成。我们发现，3 和 4 可抑制类人巨噬细胞对蛋白溶解酶颗粒的吞噬作用。有趣的是，3 和 4b 同时存在时，其抑制活性会协同增强。其他与拉巴旦相关的二萜（13-16 和 23-28）几乎没有抑制活性。3 和 4 的这种协同抑制作用可能会进一步损害吞噬细胞的功能，从而导致结核杆菌的致病性。
• Proposed Mechanism for the Reaction Catalyzed by a Diterpene Cyclase, Aphidicolan-16β-ol Synthase:  Experimental Results on Biomimetic Cyclization and Examination of the Cyclization Pathway by ab Initio Calculations
  作者：Hideaki Oikawa、Kensuke Nakamura、Hiroaki Toshima、Tomonobu Toyomasu、Takeshi Sassa

  DOI：10.1021/ja025830m

  日期：2002.8.1

  Lewis acid-catalyzed cyclizations and rearrangements. Isolation of these products in an aphidicolin-producing fungus led us to speculate that the mechanism of the ACS-catalyzed cyclization reaction is the same as that of a nonenzymatic reaction. Ab initio calculations of the acid-catalyzed reaction intermediates and the transition states indicate that the overall reaction catalyzed by ACS is an exothermic

  为了研究由 aphidicolan-16beta-ol 合酶 (ACS) 催化的环化反应的机制，ACS 是双萜 aphidicolin 生物合成的关键酶，是 DNA 聚合酶 α 的特异性抑制剂，2a 的骨架重排和 4b 的仿生环化是受雇。反应产物的结构反映了倒数第二个阳离子中间体，使我们能够为路易斯酸催化的环化和重排提出详细的反应途径。在产生 aphidicolin 的真菌中分离这些产物使我们推测 ACS 催化的环化反应的机制与非酶促反应的机制相同。酸催化反应中间体和过渡态的从头算计算表明，ACS 催化的整个反应是放热过程，尽管反应是通过能量不利的二级阳离子类过渡态进行的。结合酸催化反应中的溶剂效应，这表明 ACS 的实际作用是提供一个模板，该模板强制中间阳离子的构象导致生产性环化，尽管人们认为活性位点中的阳离子中间体和芳香族氨基酸残基对于酶催化很重要。这项研究提供了关于各种阳离子种类的作用的重要信息，尤其是二级阳离子类结构，