[2-(4-Hydroxy-phenyl)-ethyl]-carbamic acid (3R,4aR,5S,6S,6aS,10S,10aR,10bS)-5,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-3-vinyl-dodecahydro-benzo[f]chromen-6-yl ester | 136327-85-0

• 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: [2-(4-Hydroxy-phenyl)-ethyl]-carbamic acid (3R,4aR,5S,6S,6aS,10S,10aR,10bS)-5,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-3-vinyl-dodecahydro-benzo[f]chromen-6-yl ester
• 英文别名: [(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-5,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-6-yl] N-[2-(4-hydroxyphenyl)ethyl]carbamate
• CAS: 136327-85-0
• 化学式: C₂₉H₄₁NO₈
• 分子量: 531.646
• InChiKey: RLAXBRLFWGMJNW-JTOWCYLCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  38
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.66
• 拓扑面积：
  146
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  在 溶剂黄146 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 [2-(4-Hydroxy-phenyl)-ethyl]-carbamic acid (3R,4aR,5S,6S,6aS,10S,10aR,10bS)-5,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-3-vinyl-dodecahydro-benzo[f]chromen-6-yl ester
  参考文献：
  名称：

  Forskolin Carbamates: Binding and Activation Studies with Type I Adenylyl Cyclase

  摘要：

  Three series of analogs were regioselectively prepared from a protected forskolin precursor to afford 7-carbamoyl-7-desacetylforskolins (series 1), 6-carbamoyl-7-desacetylforskolins (series 2), and 6-carbamoylforskolins (series 3). The analogs were pharmacologically evaluated for binding (IC50) to and activation (EC(50)) of type I adenylyl cyclase in membranes from stably transfected Sig cell lines expressing a single adenylate cyclase subtype. The following ranges were determined for the IC50's and EC(50)'s of each individual series: series 1, IC50 = 43-1600 nM, EC(50) = 0.5-9.6 mu M; series 2, IC50 = 65-680 nM, EC(50) = 0.63-6.5 mu M; series 3, IC50 = 21-271 nM, EC(50) = 0.5-8.1 mu M (forskolin IC50 = 41 nM and EC(50) = 0.5 mu M). Activation paralleled binding; however, some analogs exhibited poor binding and good activation whereas others demonstrated good binding but poor activation. Steric bulk tended to diminish binding and activation when at the 6- or 7-position, although bulk was accommodated at the 6-position if the 7-site was reacetylated. Acylation of the 7-position by the carbamoyl linker or acetyl was important for obtaining good binding and activation; however, the effect was more pronounced with binding. For both binding and activation, small, linear, lipophilic substituents (propyl, allyl, isopropyl) are well tolerated at the 7-position but less so in the 6-position, even when the 7-site is reacetylated. Planar aromatic moieties (phenyl and 2-pyridinyl) demonstrated moderate to good potency for binding and activation when located at either the 6- or 7-positions. There is an overall trend toward increasing potency for both binding and activation with polar substituents.

  DOI：

  10.1021/jm960191+

文献信息

• (Aminoalkyl)carbamates of forskolin: intermediates for the synthesis of functionalized derivatives of forskolin with different specificities for adenylyl cyclase and the glucose transporter
  作者：Joan D. Robbins、Antonio Laurenza、Raymond W. Kosley、Gerard J. O'Malley、Bettina Spahl、Kenneth B. Seamon

  DOI：10.1021/jm00115a009

  日期：1991.11

  (Aminoalkyl)carbamates of forskolin were synthesized at the 6- and 7-hydroxyl positions of forskolin with the length of the alkyl chain varying from ethyl to heptyl. Two of these derivatives, 7-[[(2-aminoethyl)amino]carbonyl]-7-desacetylforskolin (2) and 6-[[(2-aminoethyl)amino]carbonyl]forskolin (3), were used to synthesize iodinated derivatives of forskolin that bind with high affinity to adenylyl cyclase in bovine brain membranes and the glucose transporter in human erythrocyte membranes, respectively. Hydroxyphenyl derivatives of forskolin were prepared from the (aminoalkyl)carbamates and tested for their ability to bind to adenylyl cyclase in bovine brain membranes and the glucose transporter in human erythrocyte membranes. The 6-derivative (18) of forskolin had a K(d) of 9 nM at adenylyl cyclase and was more potent than either the 7-derivatives or the 6-derivatives of 7-desacetylforskolin. The 7-derivatives were more potent at binding to the glucose transporter than forskolin. In contrast, the 6-derivatives had K(d)'s > 100-mu-M at the glucose transporter. Isothiocyanates and N-bromoacetyl derivatives were synthesized from 2 and 3 as potential alkylating agents for forskolin binding sites. The alkylating agents produced an irreversible loss of forskolin binding to adenylyl cyclase. In contrast, the alkylating agents bound reversibly to the glucose transporter.

  在 Forskolin 的 6-和 7-羟基位置上，合成了一系列长度从乙基到庚基的 (氨基烷基)碳酸酯衍生物。其中两种衍生物，即 7-[[(2-氨基乙基)氨基]羰基]-7-去乙酰基 Forskolin（2）和 6-[[(2-氨基乙基)氨基]羰基]Forskolin（3），被用于合成碘化 Forskolin 衍生物。这些碘化衍生物能够高亲和力地结合到牛脑膜中的腺苷酸环化酶以及人红细胞膜中的葡萄糖转运体中。此外，从这些 (氨基烷基)碳酸酯衍生物还制备了羟基苯基 Forskolin 衍生物，并测试了它们与腺苷酸环化酶和葡萄糖转运体的结合能力。其中，Forskolin 的 6-位衍生物（18）在腺苷酸环化酶上的 Kd 值为 9 nM，相比 7-位衍生物或 7-去乙酰基 Forskolin 的 6-位衍生物，显示出更强的活性。在葡萄糖转运体的结合中，7-位衍生物的活性高于 Forskolin，而 6-位衍生物在葡萄糖转运体上的 Kd 值则大于 100 μM。另外，从化合物 2 和 3 合成了异硫氰酸酯和 N-溴代乙酰基衍生物，作为潜在的烷基化试剂用于 Forskolin 结合位点的修饰。这些烷基化试剂导致了 Forskolin 与腺苷酸环化酶结合的不可逆丧失。然而，在葡萄糖转运体上，这些烷基化试剂的结合则是可逆的。