<2S,2(1R),3S,6R,8S,8(3S),9R>-2-(4-Hydroxy-1-methylbutyl)-3,9-dimethyl-8-(3-methyl-4-pentenyl)-1,7-dioxaspiro<5.5>undecane | 165961-54-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: <2S,2(1R),3S,6R,8S,8(3S),9R>-2-(4-Hydroxy-1-methylbutyl)-3,9-dimethyl-8-(3-methyl-4-pentenyl)-1,7-dioxaspiro<5.5>undecane
• 英文别名: (2S,2(1R),3S,6R,8S,8(3S),9R)-2-(4-hydroxy-1-methylbutyl)-8-(3-methyl-4-pentenyl)-3,9-dimethyl-1,7-dioxaspiro[5.5]undecane；(4R)-4-[(2S,3S,6R,8S,9R)-3,9-dimethyl-8-[(3S)-3-methylpent-4-enyl]-1,7-dioxaspiro[5.5]undecan-2-yl]pentan-1-ol
• CAS: 165961-54-6
• 化学式: C₂₂H₄₀O₃
• 分子量: 352.558
• InChiKey: VCSGZLLSOXAENS-CUCLYRJJSA-N

物化性质

• 沸点：
  444.4±15.0 °C(Predicted)
• 密度：
  0.97±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  <2S,2(1R),3S,6R,8S,8(3S),9R>-2-(4-Hydroxy-1-methylbutyl)-3,9-dimethyl-8-(3-methyl-4-pentenyl)-1,7-dioxaspiro<5.5>undecane 在 bis(acetylacetonate)oxovanadium 、 palladium dichloride 2,6-二甲基吡啶 、 叔丁基过氧化氢 、 4-二甲氨基吡啶 、 重铬酸吡啶 、 3 A molecular sieve 、 4 A molecular sieve 、 氢氟酸 、 水 、 氧气 、 三乙基硅基三氟甲磺酸酯 、 四氯化钛 、 三乙基硼氢化锂 、 戴斯-马丁氧化剂 、 三乙胺 、 copper(l) chloride 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 40.5h， 生成 互变霉素
  参考文献：
  名称：

  Total Synthesis of Tautomycin

  摘要：

  A convergent stereocontrolled synthesis of the antifungal antibiotic tautomycin, a potent protein phosphatases inhibitor, has been achieved first via key aldol coupling of two large subunits, a right-hand C-1-C-21 ketone and a left-hand aldehyde (left from C-22). The C-1-C-10 segment was synthesized through a remote stereochemical control process using a spiroketal template. After joining with the C-11-C-18 segment, the spiroketal moiety was selectively constructed. Then the right-hand C-1-C-21 ketone was synthesized via Roush asymmetric crotylboration. The left-hand aldehyde was prepared from a C-21-C-26 Segment and a dialkylmaleic anhydride segment. Completely stereoselective assemblage of the two subunits, the right-hand and the left-hand, was achieved by employing the Mukaiyama aldol reaction. Further functional group manipulations including desilylation, oxidation at C-2, and deprotection of tert-butyl ester with concomitant anhydride formation provided tautomycin which was identical with the natural product. As a preliminary study, derivatizations and degradation of the natural product were also examined to support the total synthesis.

  DOI：

  10.1021/jo00121a026
• 作为产物：
  描述：

  (2R,3R,6R,8R,8(1R),9S)-2-hydroxymethyl-8-(2-hydroxy-1-methylethyl)-3,9-dimethyl-1,7-dioxaspiro[5.5]undecane 在 palladium dihydroxide 吡啶 、 4-二甲氨基吡啶 、 sodium amalgam 、 lithium aluminium tetrahydride 、 正丁基锂 、 potassium tert-butylate 、 氢气 、 碳酸氢钠 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 11.42h， 生成 <2S,2(1R),3S,6R,8S,8(3S),9R>-2-(4-Hydroxy-1-methylbutyl)-3,9-dimethyl-8-(3-methyl-4-pentenyl)-1,7-dioxaspiro<5.5>undecane
  参考文献：
  名称：

  互变霉素的合成研究。第2部分：基于复杂分子的区域选择性酶乙酰化的Ichihara片段的合成

  摘要：

  实现了互变异构体的正式合成，它可以抑制1型和2A型蛋白磷酸酶。螺二元醇21由醇2或11合成。用脂肪酶“ Amano PS”对21进行区域选择性酶促乙酰化，以90％的收率得到单乙酸酯23，基于Julia偶联和Wittig同源性将其转化为Ichihara的中间体31。

  DOI：

  10.1016/j.tet.2005.10.013

文献信息

• Synthesis of a C1−C21 Subunit of the Protein Phosphatase Inhibitor Tautomycin:  A Formal Total Synthesis
  作者：James A. Marshall、Mathew M. Yanik

  DOI：10.1021/jo0056951

  日期：2001.2.1

  The synthesis of a C1-C21 subunit of tautomycin is described. The convergent route employs enantioenriched allenylstannane and zinc reagents derived from (S)-3-butyn-2-ol methanesulfonate. These reagents react with appropriate aldehyde segments to yield syn and anti adducts with high diastereoselectivity. The derived lithioalkynes are joined stepwise to a CO equivalent, (MeONMe)2C=O, to afford an intermediate

  描述了互变霉素C1-C21亚基的合成。收敛路线采用了对映体富集的烯丙基锡烷和衍生自（S）-3-butyn-2-ol甲磺酸盐的锌试剂。这些试剂与适当的醛链段反应，以高非对映选择性产生顺式和反加合物。将衍生的硫代炔烃逐步连接至CO当量（MeONMe）2 C ＝ O，以提供中间体酮，该中间体酮在酸处理后转化为互变异构体的核心螺缩酮部分。通过将上述烯丙基锌试剂另一种添加到螺酮醛中来进行链延长，以高非对映选择性进行，以安装剩余的立体中心。所得的炔丙醇加合物通过炔烃的分子内氢化硅烷化和衍生的五元硅氧烷的Tamoo氧化而转化为甲基酮。该酮被证明与张伯林在先前的互变异构全合成中使用的中间体相同。
• Synthetic study on tautomycin. Stereocontrolled synthesis of C(1)C(18) fragment using a strategy of selective reduction of spiroketal
  作者：Masato Oikawa、Hideaki Oikawa、Akitami Ichihara

  DOI：10.1016/s0040-4039(00)74091-3

  日期：1993.7

  A stereocontrolled synthesis of C(1)-C(18) fragment of tautomycin is accomplished employing asymmetric crotylboration, selective reduction of spiroketal, and addition of crotylstannane as the key steps.
• Total Synthesis of Tautomycin
  作者：Masato Oikawa、Tohru Ueno、Hideaki Oikawa、Akitami Ichihara

  DOI：10.1021/jo00121a026

  日期：1995.8

  A convergent stereocontrolled synthesis of the antifungal antibiotic tautomycin, a potent protein phosphatases inhibitor, has been achieved first via key aldol coupling of two large subunits, a right-hand C-1-C-21 ketone and a left-hand aldehyde (left from C-22). The C-1-C-10 segment was synthesized through a remote stereochemical control process using a spiroketal template. After joining with the C-11-C-18 segment, the spiroketal moiety was selectively constructed. Then the right-hand C-1-C-21 ketone was synthesized via Roush asymmetric crotylboration. The left-hand aldehyde was prepared from a C-21-C-26 Segment and a dialkylmaleic anhydride segment. Completely stereoselective assemblage of the two subunits, the right-hand and the left-hand, was achieved by employing the Mukaiyama aldol reaction. Further functional group manipulations including desilylation, oxidation at C-2, and deprotection of tert-butyl ester with concomitant anhydride formation provided tautomycin which was identical with the natural product. As a preliminary study, derivatizations and degradation of the natural product were also examined to support the total synthesis.
• Synthetic study of tautomycin. Part 2: Synthesis of Ichihara's fragment based on regioselective enzymatic acetylation of complex molecule
  作者：Yusuke Ishii、Shinji Nagumo、Takayuki Arai、Masami Akuzawa、Norio Kawahara、Hiroyuki Akita

  DOI：10.1016/j.tet.2005.10.013

  日期：2006.1

  Formal synthesis of tautomycin, which inhibits type 1 and type 2A protein phosphatases, was achieved. Spiroketal diol 21 was synthesized from alcohol 2 or 11. The regioselective enzymatic acetylation of 21 with the lipase ‘Amano PS’ gave monoacetate 23 in 90% yield, which was converted into Ichihara's intermediate 31 based on Julia coupling and Wittig homologation.

  实现了互变异构体的正式合成，它可以抑制1型和2A型蛋白磷酸酶。螺二元醇21由醇2或11合成。用脂肪酶“ Amano PS”对21进行区域选择性酶促乙酰化，以90％的收率得到单乙酸酯23，基于Julia偶联和Wittig同源性将其转化为Ichihara的中间体31。