Octanoic acid (2S,3S,6R)-6-allyl-2-[2-(tert-butyl-dimethyl-silanyloxy)-1,1-dimethyl-ethyl]-2-methoxy-4-[1-methoxycarbonyl-meth-(E)-ylidene]-tetrahydro-pyran-3-yl ester | 343601-14-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: Octanoic acid (2S,3S,6R)-6-allyl-2-[2-(tert-butyl-dimethyl-silanyloxy)-1,1-dimethyl-ethyl]-2-methoxy-4-[1-methoxycarbonyl-meth-(E)-ylidene]-tetrahydro-pyran-3-yl ester
• 英文别名: [(2S,3S,4E,6R)-2-[1-[tert-butyl(dimethyl)silyl]oxy-2-methylpropan-2-yl]-2-methoxy-4-(2-methoxy-2-oxoethylidene)-6-prop-2-enyloxan-3-yl] octanoate
• CAS: 343601-14-9
• 化学式: C₃₀H₅₄O₇Si
• 分子量: 554.84
• InChiKey: SJUHRUVQGLXGNN-AGCDVTSRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.11
• 重原子数：
  38
• 可旋转键数：
  18
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  80.3
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Octanoic acid (2S,3S,6R)-6-allyl-2-[2-(tert-butyl-dimethyl-silanyloxy)-1,1-dimethyl-ethyl]-2-methoxy-4-[1-methoxycarbonyl-meth-(E)-ylidene]-tetrahydro-pyran-3-yl ester 在 potassium carbonate hydroquinindine-2,5-diphenyl-4,6-pyrimidinediyl diether 、 potassium dioxotetrahydroxoosmate(VI) 、 Dimethylzinc 、 叔丁基锂 、 碳酸氢钠 、 戴斯-马丁氧化剂 、 triethylamine tris(hydrogen fluoride) 、 potassium hexacyanoferrate(III) 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 水 、 甲苯 、 叔丁醇 、 正戊烷 为溶剂， 反应 110.0h， 生成
  参考文献：
  名称：

  The Practical Synthesis of a Novel and Highly Potent Analogue of Bryostatin

  摘要：

  Macrocycle 1 is a new highly potent analogue of bryostatin 1, a promising anti-cancer agent currently in human clinical trials. In vitro, 1 displays picomolar affinity for PKC and exhibits over 100-fold greater potency than bryostatin 1 when tested against various human cancer cell lines. Macrocycle 1 can be generated in clinically required amounts by chemical synthesis in only 19 steps (LLS) and represents a new clinical lead for the treatment of cancer.

  DOI：

  10.1021/ja027509+
• 作为产物：
  描述：

  tert-butyl-dimethyl-[2-methyl-2-[(2S)-2-prop-2-enyl-3,4-dihydro-2H-pyran-6-yl]propoxy]silane 在 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 N-甲基吲哚酮 、 cerium(III) chloride 、 四丙基高钌酸铵 、 4 A molecular sieve 、 碳酸氢钠 、 potassium carbonate 、 达卡巴嗪 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 48.17h， 生成 Octanoic acid (2S,3S,6R)-6-allyl-2-[2-(tert-butyl-dimethyl-silanyloxy)-1,1-dimethyl-ethyl]-2-methoxy-4-[1-methoxycarbonyl-meth-(E)-ylidene]-tetrahydro-pyran-3-yl ester
  参考文献：
  名称：

  The Practical Synthesis of a Novel and Highly Potent Analogue of Bryostatin

  摘要：

  Macrocycle 1 is a new highly potent analogue of bryostatin 1, a promising anti-cancer agent currently in human clinical trials. In vitro, 1 displays picomolar affinity for PKC and exhibits over 100-fold greater potency than bryostatin 1 when tested against various human cancer cell lines. Macrocycle 1 can be generated in clinically required amounts by chemical synthesis in only 19 steps (LLS) and represents a new clinical lead for the treatment of cancer.

  DOI：

  10.1021/ja027509+

文献信息

• Function-Oriented Synthesis: Design, Synthesis, and Evaluation of Highly Simplified Bryostatin Analogues
  作者：Paul A. Wender、Jack L. Sloane、Quang H. Luu-Nguyen、Yasuyuki Ogawa、Akira J. Shimizu、Steven M. Ryckbosch、Jefferson H. Tyler、Clayton Hardman

  DOI：10.1021/acs.joc.0c01988

  日期：2020.12.4

  affinities also exhibited bryostatin-like PKC translocation kinetics in vitro, indicating rapid cell permeation and engagement of its PKC target. This study exemplifies the power of function-oriented synthesis in reducing structural complexity by activity-informed design, thus enhancing synthetic accessibility, while still maintaining function (biological activity), collectively providing new leads for

  我们使用面向功能的合成策略，设计、合成和评估了迄今为止报道的最简单的苔藓抑素 1 类似物，其中苔藓抑素的 A 环和 B 环被戊二酸连接基取代。这些类似物，一种没有 C26-甲基，一种带有 C26-甲基，表现出截然不同的蛋白激酶 C (PKC) 亚型亲和力。前者表现出与K i < 5 nM 的几种 PKC 亚型的苔藓抑素样结合，而后者表现出的 PKC 亲和力降低了约 180 倍。具有苔藓抑素样 PKC 亲和力的类似物也在体外表现出苔藓抑素样 PKC 易位动力学, 表明其 PKC 目标的快速细胞渗透和参与。这项研究举例说明了面向功能的合成在通过活动知情设计降低结构复杂性方面的力量，从而提高了合成的可及性，同时仍保持功能（生物活性），共同为解决 PKC 调节剂所展示的越来越多的治疗适应症列表提供了新的线索.
• The Practical Synthesis of a Novel and Highly Potent Analogue of Bryostatin
  作者：Paul A. Wender、Jeremy L. Baryza、Chad E. Bennett、F. Christopher Bi、Stacey E. Brenner、Michael O. Clarke、Joshua C. Horan、Cindy Kan、Emmanuel Lacôte、Blaise Lippa、Peter G. Nell、Tim M. Turner

  DOI：10.1021/ja027509+

  日期：2002.11.1

  Macrocycle 1 is a new highly potent analogue of bryostatin 1, a promising anti-cancer agent currently in human clinical trials. In vitro, 1 displays picomolar affinity for PKC and exhibits over 100-fold greater potency than bryostatin 1 when tested against various human cancer cell lines. Macrocycle 1 can be generated in clinically required amounts by chemical synthesis in only 19 steps (LLS) and represents a new clinical lead for the treatment of cancer.