(3S)-3-[(tert-butyldimethylsilyl)oxy]-4-methyl-5-hexenal | 220249-57-0

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: (3S)-3-[(tert-butyldimethylsilyl)oxy]-4-methyl-5-hexenal
• 英文别名: (3S,4R)-3-[(tert-butyldimethylsilyl)oxy]-4-methyl-5-hexenal；(3S,4R)-3-(tert-butyldimethylsilyloxy)-4-methylhex-5-enal；(3S,4R)-3-[tert-butyl(dimethyl)silyl]oxy-4-methylhex-5-enal
• CAS: 220249-57-0
• 化学式: C₁₃H₂₆O₂Si
• 分子量: 242.434
• InChiKey: KULUFLSKKBSAMO-NEPJUHHUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.79
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3S)-3-[(tert-butyldimethylsilyl)oxy]-4-methyl-5-hexenal 在 palladium diacetate 4-二甲氨基吡啶 、 amberlyst-15 、 四丁基氟化铵 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 lithium chloride 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 33.75h， 生成 desepoxyarenastatin A
  参考文献：
  名称：

  Total Synthesis of Cryptophycin-24 (Arenastatin A) Amenable to Structural Modifications in the C16 Side Chain

  摘要：

  Two efficient protocols for the synthesis of tert-butyl (5S,6R,2E,7E)-5-[(tert-butyldimethylsily oxy]-6-methyl-8-phenyl-2,7-octadienoate, a major component of the cryptophycins, are reported. The first utilized the Noyori reduction and Frater alkylation of methyl 5-benzyloxy-3-oxopentanoate to set two stereogenic centers, which became the C16 hydroxyl and C1' methyl oft-he cryptophycins. The second approach started from 3-p-methoxybenzyloxypropanal and a crotyl borane reagent derived from (-)-alpha -pinene to set both stereocenters in a single step and provided the dephenyl analogue, tert-butyl(5S,6R,2E)-5-[(tert-butyldimethylsilyl)oxy]-6 -methyl-2,7 -octadienoate, in five steps. This compound was readily converted to the 8-phenyl compound via Heck coupling. The silanyloxy esters were efficiently deprotected and coupled to the C2-C10 amino acid fragment to provide desepoxyarenastatin A and its dephenyl analogue. The terminal olefin of the latter was further elaborated via Heck coupling. Epoxidation provided cryptophycin-24 (arenastatin A).

  DOI：

  10.1021/jo000767+
• 作为产物：
  描述：

  1-(4-methoxybenzyloxy)-4-methylhex-5-en-3-ol 在 2,6-二甲基吡啶 、 N-甲基吲哚酮 、 四丙基高钌酸铵 、 水 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 0.67h， 生成 (3S)-3-[(tert-butyldimethylsilyl)oxy]-4-methyl-5-hexenal
  参考文献：
  名称：

  Enantioselective synthesis of A 3′-dephenylcryptophycin synthon

  摘要：

  An enantioselective synthesis of tert-butyl (5S,6R)-(E)-5-tert-butyldimethylsilyloxy-6-methy l-2,7-octadienoate, a precursor for the synthesis of the antimitotic macrolides cryptophycin A and arenastatin A (cryptophycin-24), is presented. The key step in the reaction sequence features a crotyl boration that sets both stereocenters that become the C16 hydroxyl and C1' methyl in the cryptophycins. Homologation of the terminal olefin via a Heck reaction is presented. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00557-5

文献信息

• Direct Generation of Acyclic Polypropionate Stereopolyads <i>via</i> Double Diastereo- and Enantioselective Iridium-Catalyzed Crotylation of 1,3-Diols: Beyond Stepwise Carbonyl Addition in Polyketide Construction
  作者：Xin Gao、Hoon Han、Michael J. Krische

  DOI：10.1021/ja204570w

  日期：2011.8.17

  cyclometalated iridium catalyst (R)-I derived from [Ir(cod)Cl](2), allyl acetate, 4-cyano-3-nitrobenzoic acid, and the chiral phosphine ligand (R)-SEGPHOS, α-methylallyl acetate engages 1,3-propanediol (1a) and 2-methyl-1,3-propanediol (1b) in double carbonyl crotylation from the alcohol oxidation level to deliver the C(2)-symmetric and pseudo-C(2)-symmetric stereopolyads 2a and 3a, respectively, with exceptional

  在使用衍生自 [Ir(cod)Cl](2)、乙酸烯丙酯、4-氰基-3-硝基苯甲酸和手性膦配体 (R)-的环金属化铱催化剂 (R)-I 进行转移氢化的条件下SEGPHOS，α-甲基烯丙基乙酸酯与 1,3-丙二醇 (1a) 和 2-甲基-1,3-丙二醇 (1b) 从醇氧化水平进行双羰基巴豆化反应，以提供 C(2)-对称和假-C (2)-对称立体多聚体 2a 和 3a，分别具有反非对映选择性和对映选择性的特殊控制。值得注意的是，聚丙酸酯立体五元组 3a 主要以 16 种可能的立体异构体中的一种形成。3a 的去对称化很容易在碘醚化形成吡喃 4 后实现。 3a 的直接生成能够显着简化先前制备的聚丙酸酯亚结构的方法，正如利福霉素 S 的 C19-C27（八步，最初在 26 步中制备）和细胞霉素 C 的 C19-C25 的合成（八步，最初以 15 步制备）所证明的。本转移氢化协议代表了聚酮化合物结构中手
• Synthesis and Cytotoxicity Studies of New Cryptophycin Analogues
  作者：Wen Lu Liu、Jian Cun Zhang、Fa Qin Jiang、Lei Fu

  DOI：10.1002/ardp.200900067

  日期：2009.10

  Two analogues of cryptophycin were synthesized and biologically evaluated for their in‐vitro cytotoxicities against several solid tumors and leukemia cell lines. The results revealed that both analogues exhibited a broad range of cytotoxic activity with observed IC50 values in the μM‐range, and compound 4 was more effective than compound 3 in most assays studied.

  合成了两种隐藻素类似物，并对其对几种实体瘤和白血病细胞系的体外细胞毒性进行了生物学评估。结果表明，两种类似物都表现出广泛的细胞毒活性，观察到的 IC50 值在 μM 范围内，在大多数研究中，化合物 4 比化合物 3 更有效。
• Cryptophycin affinity labels: synthesis and biological activity of a benzophenone analogue of cryptophycin-24
  作者：Ramdas Vidya、MariJean Eggen、Gunda I. Georg、Richard H. Himes

  DOI：10.1016/s0960-894x(02)01023-5

  日期：2003.2

  An efficient synthesis of a C16 side chain benzophenone analogue of cryptophycin-24 using a crotylboration reaction and Heck coupling as key steps is described. In an in vitro tubulin assembly assay, the benzophenone analogue of the beta isomer (IC(50)=7.4 microM) is twice as active as cryptophycin-24 (IC(50)=15 microM).

  描述了使用巴豆基硼化反应和Heck偶联作为关键步骤，高效合成隐藻霉素24的C16侧链二苯甲酮类似物。在体外微管蛋白组装测定中，β异构体的二苯甲酮类似物（IC（50）= 7.4 microM）的活性是隐藻素-24（IC（50）= 15 microM）的两倍。
• Total Synthesis of Cryptophycin-24 (Arenastatin A) Amenable to Structural Modifications in the C16 Side Chain
  作者：MariJean Eggen、Craig J. Mossman、Suzanne B. Buck、Sajiv K. Nair、Laxminarayan Bhat、Syed M. Ali、Emily A. Reiff、Thomas C. Boge、Gunda I. Georg

  DOI：10.1021/jo000767+

  日期：2000.11.1

  Two efficient protocols for the synthesis of tert-butyl (5S,6R,2E,7E)-5-[(tert-butyldimethylsily oxy]-6-methyl-8-phenyl-2,7-octadienoate, a major component of the cryptophycins, are reported. The first utilized the Noyori reduction and Frater alkylation of methyl 5-benzyloxy-3-oxopentanoate to set two stereogenic centers, which became the C16 hydroxyl and C1' methyl oft-he cryptophycins. The second approach started from 3-p-methoxybenzyloxypropanal and a crotyl borane reagent derived from (-)-alpha -pinene to set both stereocenters in a single step and provided the dephenyl analogue, tert-butyl(5S,6R,2E)-5-[(tert-butyldimethylsilyl)oxy]-6 -methyl-2,7 -octadienoate, in five steps. This compound was readily converted to the 8-phenyl compound via Heck coupling. The silanyloxy esters were efficiently deprotected and coupled to the C2-C10 amino acid fragment to provide desepoxyarenastatin A and its dephenyl analogue. The terminal olefin of the latter was further elaborated via Heck coupling. Epoxidation provided cryptophycin-24 (arenastatin A).
• Enantioselective synthesis of A 3′-dephenylcryptophycin synthon
  作者：MariJean Eggen、Gunda I. Georg

  DOI：10.1016/s0960-894x(98)00557-5

  日期：1998.11

  An enantioselective synthesis of tert-butyl (5S,6R)-(E)-5-tert-butyldimethylsilyloxy-6-methy l-2,7-octadienoate, a precursor for the synthesis of the antimitotic macrolides cryptophycin A and arenastatin A (cryptophycin-24), is presented. The key step in the reaction sequence features a crotyl boration that sets both stereocenters that become the C16 hydroxyl and C1' methyl in the cryptophycins. Homologation of the terminal olefin via a Heck reaction is presented. (C) 1998 Elsevier Science Ltd. All rights reserved.