(1S-(1α,3α,4β,5α,6α,7β))-1-(3,3-dimethoxypropyl)-4,6,7-trihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid 3,4,5-tris(1,1-dimethylethyl) ester | 185155-26-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (1S-(1α,3α,4β,5α,6α,7β))-1-(3,3-dimethoxypropyl)-4,6,7-trihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid 3,4,5-tris(1,1-dimethylethyl) ester
• 英文别名: tritert-butyl (1S,3S,4S,5R,6R,7R)-1-(3,3-dimethoxypropyl)-4,6,7-trihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylate
• CAS: 185155-26-4
• 化学式: C₂₆H₄₄O₁₃
• 分子量: 564.628
• InChiKey: BWDXSKVDRRZJPQ-LXBOXMHASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  39
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  177
• 氢给体数：
  3
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  (1S-(1α,3α,4β,5α,6α,7β))-1-(3,3-dimethoxypropyl)-4,6,7-trihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid 3,4,5-tris(1,1-dimethylethyl) ester 在 4 A molecular sieve 、 4-甲基苯磺酸吡啶 作用下， 以 苯 为溶剂， 反应 0.12h， 生成 (1R,3R,8S-(1α,2α,5α,10α,11β))-5-methoxy-2,11-dihydroxy-4,9,12-trioxatricyclo[6.3.1.0^3,8]dodecane-1,10,11-tricarboxylic acid 1,10,11-tris(1,1-dimethylethyl) ester 、 (1R,3R,8S-(1α,2α,5β,10α,11β))-5-methoxy-2,11-dihydroxy-4,9,12-trioxatricyclo[6.3.1.0^3,8]dodecane-1,10,11-tricarboxylic acid 1,10,11-tris(1,1-dimethylethyl) ester
  参考文献：
  名称：

  Total Synthesis of Zaragozic Acid A (Squalestatin S1). Degradation to a Relay Compound and Reassembly of the Natural Product

  摘要：

  Zaragozic acid A (squalestatin S1) (1) was converted into the simpler derivative 2, which was reconverted into the natural product, thus establishing 2 as a viable relay compound for total synthesis of 1. The degradation (Scheme 1) consisted of formation of the tri-tert-butyl ester (3), from which the two side chains were sequentially removed to obtain 8. Aldehyde 8 was converted into dimethyl acetal 2 in standard fashion. The C6 acyl side chain 14 was prepared from (S)-2-methylbutanol (''active amyl alcohol''), and the desired 4S configuration was obtained by use of Evans asymmetric enolate methylation (Scheme 2). The C1 alkyl side chain was prepared as stannane 23a from (R)-2-methyl-3-phenylpropanol (21) as shown in Scheme 5. For conversion of 2 back into zaragozic acid A, the dimethyl acetal was first converted into the cyclic acetal 17, thus protecting the C7 hydroxyl group. The remaining hydroxyl group was then acylated with acid 14 to obtain 18, which was transformed into aldehyde 20 (Scheme 4). The C1 alkyl chain was elaborated by the addition of a chiral alpha-alkoxyorganocerium reagent, obtained from 23a, to aldehyde 20. The resulting mixture of diastereomeric secondary alcohols was converted into zaragozic acid A (1) in six steps (Scheme 6).

  DOI：

  10.1021/jo961533m
• 作为产物：
  描述：

  [1S-(1α(4S,5R),3α,4β,5α,6α,7β)]-1-(4-hydroxy-5-methyl-3-methylene-6-phenylhexyl)-4,6,7-trihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid 3,4,5-tris(1,1-dimethylethyl) ester 在 lead(IV) acetate 、 sodium tetrahydroborate 、 二甲基硫 、 4-甲基苯磺酸吡啶 、 臭氧 作用下， 以 甲醇 、 苯 为溶剂， 反应 3.55h， 生成 (1S-(1α,3α,4β,5α,6α,7β))-1-(3,3-dimethoxypropyl)-4,6,7-trihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid 3,4,5-tris(1,1-dimethylethyl) ester
  参考文献：
  名称：

  Total Synthesis of Zaragozic Acid A (Squalestatin S1). Degradation to a Relay Compound and Reassembly of the Natural Product

  摘要：

  Zaragozic acid A (squalestatin S1) (1) was converted into the simpler derivative 2, which was reconverted into the natural product, thus establishing 2 as a viable relay compound for total synthesis of 1. The degradation (Scheme 1) consisted of formation of the tri-tert-butyl ester (3), from which the two side chains were sequentially removed to obtain 8. Aldehyde 8 was converted into dimethyl acetal 2 in standard fashion. The C6 acyl side chain 14 was prepared from (S)-2-methylbutanol (''active amyl alcohol''), and the desired 4S configuration was obtained by use of Evans asymmetric enolate methylation (Scheme 2). The C1 alkyl side chain was prepared as stannane 23a from (R)-2-methyl-3-phenylpropanol (21) as shown in Scheme 5. For conversion of 2 back into zaragozic acid A, the dimethyl acetal was first converted into the cyclic acetal 17, thus protecting the C7 hydroxyl group. The remaining hydroxyl group was then acylated with acid 14 to obtain 18, which was transformed into aldehyde 20 (Scheme 4). The C1 alkyl chain was elaborated by the addition of a chiral alpha-alkoxyorganocerium reagent, obtained from 23a, to aldehyde 20. The resulting mixture of diastereomeric secondary alcohols was converted into zaragozic acid A (1) in six steps (Scheme 6).

  DOI：

  10.1021/jo961533m

文献信息

• Total Synthesis of Zaragozic Acid A (Squalestatin S1). Synthesis of the Relay Compound
  作者：Stéphane Caron、Doris Stoermer、Anna Kathryn Mapp、Clayton H. Heathcock

  DOI：10.1021/jo961534e

  日期：1996.1.1

  Compound 2 has been prepared from the 1,6-anhydropyranohexose 3. The key process for elaborating the 1,7-dioxabicyclo[3.2.1]octane core of the zaragozic acids is addition of an organometallic reagent to lactone 6 and treatment of the resulting 1,2,3-trihydroxy-6-oxo ethylene acetal with acid. Use of the cerium(III) reagent of 4-bromo-1-butene in this process provided 7 in excellent yield, unaccompanied by the isomeric 1,6-anhydropyranose isomer. The remaining two carboxy groups of the zaragozic acid core were added by addition of the lithium enolate of 8 to formaldehyde, to obtain 9, and cerium(III)-mediated addition of vinyllithium to ketone 10. The latter addition was shown by 2D H-1 NMR experiments to provide the relative configuration found in the zaragozic acids. Similar stereoselective additions were observed with 2-furyllithium and (5-methyl-2-furyl)-lithium, but the resulting adducts are resistant to ozonolysis. The synthesis of 2 completes a total synthesis of zaragozic acid A (squalestatin S1) (1).
• Total Synthesis of Zaragozic Acid A (Squalestatin S1). Degradation to a Relay Compound and Reassembly of the Natural Product
  作者：Doris Stoermer、Stéphane Caron、Clayton H. Heathcock

  DOI：10.1021/jo961533m

  日期：1996.1.1

  Zaragozic acid A (squalestatin S1) (1) was converted into the simpler derivative 2, which was reconverted into the natural product, thus establishing 2 as a viable relay compound for total synthesis of 1. The degradation (Scheme 1) consisted of formation of the tri-tert-butyl ester (3), from which the two side chains were sequentially removed to obtain 8. Aldehyde 8 was converted into dimethyl acetal 2 in standard fashion. The C6 acyl side chain 14 was prepared from (S)-2-methylbutanol (''active amyl alcohol''), and the desired 4S configuration was obtained by use of Evans asymmetric enolate methylation (Scheme 2). The C1 alkyl side chain was prepared as stannane 23a from (R)-2-methyl-3-phenylpropanol (21) as shown in Scheme 5. For conversion of 2 back into zaragozic acid A, the dimethyl acetal was first converted into the cyclic acetal 17, thus protecting the C7 hydroxyl group. The remaining hydroxyl group was then acylated with acid 14 to obtain 18, which was transformed into aldehyde 20 (Scheme 4). The C1 alkyl chain was elaborated by the addition of a chiral alpha-alkoxyorganocerium reagent, obtained from 23a, to aldehyde 20. The resulting mixture of diastereomeric secondary alcohols was converted into zaragozic acid A (1) in six steps (Scheme 6).