14-(3-hydroxy-4-methoxyphenyl)-2,11,12-trimethoxy-6-oxo-6H-[1]benzopyrano[4',3':4,5]pyrrolo[2,1-a]isoquinolin-3-yl 2,2,2-trichloroethyl sulfate | 895632-77-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 14-(3-hydroxy-4-methoxyphenyl)-2,11,12-trimethoxy-6-oxo-6H-[1]benzopyrano[4',3':4,5]pyrrolo[2,1-a]isoquinolin-3-yl 2,2,2-trichloroethyl sulfate
• 英文别名: [12-(3-Hydroxy-4-methoxyphenyl)-8,16,17-trimethoxy-3-oxo-4-oxa-1-azapentacyclo[11.8.0.02,11.05,10.014,19]henicosa-2(11),5,7,9,12,14,16,18,20-nonaen-7-yl] 2,2,2-trichloroethyl sulfate；[12-(3-hydroxy-4-methoxyphenyl)-8,16,17-trimethoxy-3-oxo-4-oxa-1-azapentacyclo[11.8.0.02,11.05,10.014,19]henicosa-2(11),5,7,9,12,14,16,18,20-nonaen-7-yl] 2,2,2-trichloroethyl sulfate
• CAS: 895632-77-6
• 化学式: C₃₁H₂₄Cl₃NO₁₁S
• 分子量: 724.957
• InChiKey: WQEIAAPPBIEEAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  47
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  149
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  14-(3-hydroxy-4-methoxyphenyl)-2,11,12-trimethoxy-6-oxo-6H-[1]benzopyrano[4',3':4,5]pyrrolo[2,1-a]isoquinolin-3-yl 2,2,2-trichloroethyl sulfate 在 甲酸铵 、 锌 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 4.0h， 以85%的产率得到lamellarin α 20-sulfate
  参考文献：
  名称：

  Divergent Synthesis of Lamellarin α 13-Sulfate, 20-Sulfate, and 13,20-Disulfate

  摘要：

  A divergent synthesis of three sulfate derivatives of lamellarin alpha, namely, lamellarin alpha 13-sulfate (2), 20-sulfate (1), and 13,20-disulfate (4) has been achieved via a common intermediate (6) in which 13-OH and 20-OH of the lamellarin core are differentially protected by MOM and benzyl groups, respectively. Compound (6) in turn was prepared using sequential Suzuki-Miyaura coupling of 3,4-dihydroxypyrrole bistriflate (7) as a key reaction.

  DOI：

  10.3987/com-09-s(s)100
• 作为产物：
  描述：

  5-溴-2-甲氧基苯酚 在 喹啉 、 盐酸 、 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 palladium 10% on activated carbon 、 三氟化硼乙醚 、 氢气 、 叔丁基锂 、 4-甲基苯磺酸吡啶 、 sodium carbonate 、 potassium carbonate 、 三乙胺 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 [双(三氟乙酰氧基)碘]苯 、 copper(II) oxide 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 丙酮 为溶剂， 反应 111.67h， 生成 14-(3-hydroxy-4-methoxyphenyl)-2,11,12-trimethoxy-6-oxo-6H-[1]benzopyrano[4',3':4,5]pyrrolo[2,1-a]isoquinolin-3-yl 2,2,2-trichloroethyl sulfate
  参考文献：
  名称：

  Synthesis, structure–activity relationships, and mechanism of action of anti-HIV-1 lamellarin α 20-sulfate analogues

  摘要：

  Lamellarin a and six different types of lamellarin alpha 20-sulfate analogues were synthesized and their structure-activity relationships were investigated using a single round HIV-1 vector infection assay. All lamellarin sulfates having pentacyclic lamellarin core exhibited anti-HIV-1 activity at a 10 mu M concentration range regardless of the number and position of the sulfate group. On the other hand, non-sulfated lamellarin alpha and ring-opened lamellarin sulfate analogues did not affect HIV-1 vector infection in similar concentrations. The lamellarin sulfates utilized in this study did not exhibit unfavorable cytotoxic effect under the concentrations tested (IC50 > 100 mu M). Confocal laser scanning microscopic analysis indicated that hydrophilic lamellarin sulfates were hardly incorporated in the cell. HIV-1 Env-mediated cell-cell fusion was suppressed by lamellarin sulfates. These results suggested that lamellarin sulfates have a novel anti-HIV-1 activity besides the previously reported integrase activity inhibition, possibly at a viral entry step of HIV-1 replication. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.030

文献信息

• The first total synthesis of lamellarin α 20-sulfate, a selective inhibitor of HIV-1 integrase
  作者：Tomohiro Yamaguchi、Tsutomu Fukuda、Fumito Ishibashi、Masatomo Iwao

  DOI：10.1016/j.tetlet.2006.03.121

  日期：2006.5

  The first total synthesis of lamellarin alpha 20-sulfate (1), a selective inhibitor of HIV-1 integrase, has been completed. The lamellarin alpha core in which 13-OH and 20-OH were differentially protected by isopropyl and benzyl groups, respectively, was constructed by using Hinsberg-type pyrrole synthesis and Suzuki-Miyaura coupling as the key reactions. The 20-sulfate was prepared by a sequence including debenzylation of 20-OBn, 2,2,2-trichloroethylsulfation of the resulting 20-OH deprotection of 13-Oi-Pr, and final reductive cleavage of the 2,2,2-trichloroethyl ester. (c) 2006 Elsevier Ltd. All rights reserved.
• Divergent Synthesis of Lamellarin α 13-Sulfate, 20-Sulfate, and 13,20-Disulfate
  作者：Masatomo Iwao、Tsutomu Fukuda、Sho Saeki、Takeshi Ohta

  DOI：10.3987/com-09-s(s)100

  日期：——

  A divergent synthesis of three sulfate derivatives of lamellarin alpha, namely, lamellarin alpha 13-sulfate (2), 20-sulfate (1), and 13,20-disulfate (4) has been achieved via a common intermediate (6) in which 13-OH and 20-OH of the lamellarin core are differentially protected by MOM and benzyl groups, respectively. Compound (6) in turn was prepared using sequential Suzuki-Miyaura coupling of 3,4-dihydroxypyrrole bistriflate (7) as a key reaction.
• Synthesis, structure–activity relationships, and mechanism of action of anti-HIV-1 lamellarin α 20-sulfate analogues
  作者：Haruka Kamiyama、Yoshinao Kubo、Hironori Sato、Naoki Yamamoto、Tsutomu Fukuda、Fumito Ishibashi、Masatomo Iwao

  DOI：10.1016/j.bmc.2011.10.030

  日期：2011.12

  Lamellarin a and six different types of lamellarin alpha 20-sulfate analogues were synthesized and their structure-activity relationships were investigated using a single round HIV-1 vector infection assay. All lamellarin sulfates having pentacyclic lamellarin core exhibited anti-HIV-1 activity at a 10 mu M concentration range regardless of the number and position of the sulfate group. On the other hand, non-sulfated lamellarin alpha and ring-opened lamellarin sulfate analogues did not affect HIV-1 vector infection in similar concentrations. The lamellarin sulfates utilized in this study did not exhibit unfavorable cytotoxic effect under the concentrations tested (IC50 > 100 mu M). Confocal laser scanning microscopic analysis indicated that hydrophilic lamellarin sulfates were hardly incorporated in the cell. HIV-1 Env-mediated cell-cell fusion was suppressed by lamellarin sulfates. These results suggested that lamellarin sulfates have a novel anti-HIV-1 activity besides the previously reported integrase activity inhibition, possibly at a viral entry step of HIV-1 replication. (C) 2011 Elsevier Ltd. All rights reserved.