(5S,9S,10S)-13-azalabda-8(17)-en-15-ol | 369363-38-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (5S,9S,10S)-13-azalabda-8(17)-en-15-ol
• 英文别名: 2-[2-[(1S,4aS,8aS)-5,5,8a-trimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]ethyl-methylamino]ethanol
• CAS: 369363-38-2
• 化学式: C₁₉H₃₅NO
• 分子量: 293.493
• InChiKey: HJWDYUMAQDDYMQ-JENIJYKNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (5S,9S,10S)-13-azalabda-8(17)-en-15-ol 在 tris(tetra-n-butylammonium) hydrogen pyrophosphate 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 8.5h， 生成 (5S,9S,10S)-13-azalabda-8(17)-en-15-yl diposphate, ammonium salt
  参考文献：
  名称：

  Bifunctional Abietadiene Synthase:  Free Diffusive Transfer of the (+)-Copalyl Diphosphate Intermediate between Two Distinct Active Sites

  摘要：

  Abietadiene synthase (AS) catalyzes two sequential, mechanistically distinct cyclizations in the conversion of geranylgeranyl diphosphate to a mixture of abietadiene double bond isomers as the initial step of resin acid biosynthesis in grand fir (Abies grandis). The first reaction converts geranylgeranyl diphosphate to the stable bicyclic intermediate (+)-copalyl diphosphate via protonation-initiated cyclization. In the second reaction, diphosphate ester ionization-initiated cyclization generates the tricyclic perhydrophenanthrene-type backbone, and is directly coupled to a 1,2-methyl migration that generates the C13 isopropyl group characteristic of the abietane family of diterpenes. Using the transition-state analogue inhibitor 14,15-dihydro-15-azageranylgeranyl diphosphate, it was demonstrated that each reaction of abietadiene synthase is carried out at a distinct active site. Mutations in two aspartate-rich motifs specifically delete one or the other activity and the location of these motifs suggests that the two active sites reside in separate domains. These mutants effectively complement each other, suggesting that the copalyl diphosphate intermediate diffuses between the two active sites in this monomeric enzyme. Free copalyl diphosphate was detected in steady-state kinetic reactions, thus conclusively demonstrating a free diffusion transfer mechanism. In addition, both mutant enzymes enhance the activity of wild-type abietadiene synthase with geranylgeranyl diphosphate as substrate. The implications of these results for the kinetic mechanism of abietadiene synthase are discussed.

  DOI：

  10.1021/ja010670k
• 作为产物：
  描述：

  Labda-8(17),13Z/E-dien-15-al 在 氢氧化钾 、 lithium aluminium tetrahydride 、 二苯基膦叠氮化物 、 碘 、 potassium carbonate 、 三乙胺 、 potassium iodide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醚 、 水 、 苯 为溶剂， 反应 58.0h， 生成 (5S,9S,10S)-13-azalabda-8(17)-en-15-ol
  参考文献：
  名称：

  Bifunctional Abietadiene Synthase:  Free Diffusive Transfer of the (+)-Copalyl Diphosphate Intermediate between Two Distinct Active Sites

  摘要：

  Abietadiene synthase (AS) catalyzes two sequential, mechanistically distinct cyclizations in the conversion of geranylgeranyl diphosphate to a mixture of abietadiene double bond isomers as the initial step of resin acid biosynthesis in grand fir (Abies grandis). The first reaction converts geranylgeranyl diphosphate to the stable bicyclic intermediate (+)-copalyl diphosphate via protonation-initiated cyclization. In the second reaction, diphosphate ester ionization-initiated cyclization generates the tricyclic perhydrophenanthrene-type backbone, and is directly coupled to a 1,2-methyl migration that generates the C13 isopropyl group characteristic of the abietane family of diterpenes. Using the transition-state analogue inhibitor 14,15-dihydro-15-azageranylgeranyl diphosphate, it was demonstrated that each reaction of abietadiene synthase is carried out at a distinct active site. Mutations in two aspartate-rich motifs specifically delete one or the other activity and the location of these motifs suggests that the two active sites reside in separate domains. These mutants effectively complement each other, suggesting that the copalyl diphosphate intermediate diffuses between the two active sites in this monomeric enzyme. Free copalyl diphosphate was detected in steady-state kinetic reactions, thus conclusively demonstrating a free diffusion transfer mechanism. In addition, both mutant enzymes enhance the activity of wild-type abietadiene synthase with geranylgeranyl diphosphate as substrate. The implications of these results for the kinetic mechanism of abietadiene synthase are discussed.

  DOI：

  10.1021/ja010670k

文献信息

• Bifunctional Abietadiene Synthase:  Free Diffusive Transfer of the (+)-Copalyl Diphosphate Intermediate between Two Distinct Active Sites
  作者：Reuben J. Peters、Matthew M. Ravn、Robert M. Coates、Rodney B. Croteau

  DOI：10.1021/ja010670k

  日期：2001.9.1

  Abietadiene synthase (AS) catalyzes two sequential, mechanistically distinct cyclizations in the conversion of geranylgeranyl diphosphate to a mixture of abietadiene double bond isomers as the initial step of resin acid biosynthesis in grand fir (Abies grandis). The first reaction converts geranylgeranyl diphosphate to the stable bicyclic intermediate (+)-copalyl diphosphate via protonation-initiated cyclization. In the second reaction, diphosphate ester ionization-initiated cyclization generates the tricyclic perhydrophenanthrene-type backbone, and is directly coupled to a 1,2-methyl migration that generates the C13 isopropyl group characteristic of the abietane family of diterpenes. Using the transition-state analogue inhibitor 14,15-dihydro-15-azageranylgeranyl diphosphate, it was demonstrated that each reaction of abietadiene synthase is carried out at a distinct active site. Mutations in two aspartate-rich motifs specifically delete one or the other activity and the location of these motifs suggests that the two active sites reside in separate domains. These mutants effectively complement each other, suggesting that the copalyl diphosphate intermediate diffuses between the two active sites in this monomeric enzyme. Free copalyl diphosphate was detected in steady-state kinetic reactions, thus conclusively demonstrating a free diffusion transfer mechanism. In addition, both mutant enzymes enhance the activity of wild-type abietadiene synthase with geranylgeranyl diphosphate as substrate. The implications of these results for the kinetic mechanism of abietadiene synthase are discussed.