(4R)-4-ethyl-4,5-dihydroxypentanal acetonide | 131703-67-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (4R)-4-ethyl-4,5-dihydroxypentanal acetonide
• 英文别名: (4R)-ethyl-4,5-dihydroxypentanal acetonide；3-[(4R)-4-ethyl-2,2-dimethyl-1,3-dioxolan-4-yl]propanal
• CAS: 131703-67-8
• 化学式: C₁₀H₁₈O₃
• 分子量: 186.251
• InChiKey: ZAEKHBVPIUDODJ-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4R)-4-ethyl-4,5-dihydroxypentanal acetonide 、 methyl 3-benzyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate 以 甲苯 为溶剂， 反应 12.0h， 生成 methyl 3-benzyl-2,3,3a,4,5,7-hexahydro-4-<(2R)-2-ethyl-2,3-(isopropylidenedioxy)propyl>-1H-pyrrolo<2,3-d>carbazole-6-carboxylate
  参考文献：
  名称：

  Enantioselective syntheses of vinblastine, leurosidine, vincovaline and 20'-epi-vincovaline

  摘要：

  The binary indole-indoline alkaloids vinblastine (1), leurosidine (13), 20'-epi-vincovaline (14a), and vincovaline (14b) were obtained by coupling of vindoline (3) to the tetracyclic intermediates 7a, 7b or 22a, 22b, followed by reduction and cyclization steps (60% overall yield for these reactions). The intermediates were obtained by enantioselective establishment of C20' through a first-step Sharpless oxidation (10a,b) and followed by a subsequent diastereomeric separation (20a,b or 21a,b). Alternatively, enantioselective control of the key secodine-type cyclization in the reaction sequence provided the tetracyclic intermediates 54 and 60 for coupling to vindoline. Selective generation of the natural (1, 13, 14a,b) or unnatural (30, 34, 35a,b) atropisomeric forms of the alkaloids was achieved through alternative closures of ring D'. The natural products were also obtained from the higher energy atropisomers by conformational inversion on heating. For the vinblastine synthesis, the overall yield was 22%.

  DOI：

  10.1021/jo00002a008
• 作为产物：
  描述：

  2-Methylene-1-butanol 在 titanium(IV) isopropylate 、 叔丁基过氧化氢 、 copper(l) iodide 、 L-(+)-酒石酸二乙酯 、 4 A molecular sieve 、 对甲苯磺酸 、 臭氧 、 三苯基膦 作用下， 以 四氢呋喃 、 异辛烷 、 二氯甲烷 、 丙酮 为溶剂， 反应 70.25h， 生成 (4R)-4-ethyl-4,5-dihydroxypentanal acetonide
  参考文献：
  名称：

  Enantioselective syntheses of vinblastine, leurosidine, vincovaline and 20'-epi-vincovaline

  摘要：

  The binary indole-indoline alkaloids vinblastine (1), leurosidine (13), 20'-epi-vincovaline (14a), and vincovaline (14b) were obtained by coupling of vindoline (3) to the tetracyclic intermediates 7a, 7b or 22a, 22b, followed by reduction and cyclization steps (60% overall yield for these reactions). The intermediates were obtained by enantioselective establishment of C20' through a first-step Sharpless oxidation (10a,b) and followed by a subsequent diastereomeric separation (20a,b or 21a,b). Alternatively, enantioselective control of the key secodine-type cyclization in the reaction sequence provided the tetracyclic intermediates 54 and 60 for coupling to vindoline. Selective generation of the natural (1, 13, 14a,b) or unnatural (30, 34, 35a,b) atropisomeric forms of the alkaloids was achieved through alternative closures of ring D'. The natural products were also obtained from the higher energy atropisomers by conformational inversion on heating. For the vinblastine synthesis, the overall yield was 22%.

  DOI：

  10.1021/jo00002a008

文献信息

• The Syntheses of 16a‘-<i>homo-</i>Leurosidine and 16a‘-<i>homo-</i>Vinblastine. Generation of Atropisomers
  作者：Martin E. Kuehne、Yong Qin、Anne E. Huot、Susan L. Bane

  DOI：10.1021/jo000250y

  日期：2001.8.1

  The synthesis of 16a'-homo-leurosidine was achieved through enantioselective generation of a ring U-seco-precursor 33 (without requirement of a chiral auxiliary). Its cyclization provided the N-b'-quaternary salt 35 with a configuration corresponding to the atropisomeric form 8a rather than 8b of the target product. On debenzylation, the amine Sa was obtained and found not to isomerize thermally to the anticipated atropisomer 8b (in contrast to its lower homologue, with its formation of natural leurosidine). However, on protonation, a 1:1 mixture of atropisomers of 16a'-homo-leurosidine was obtained. A synthesis of 16a'-homo-vinblastine provided two atropisomers 5a and 5b for the free base at equilibrium (1:2.3 at room temperature in CDCl3), with a shift to the major conformer 5b with increasing solvent acidity or decreasing temperature. The synthesis was achieved through a stereoselective inversion of the tertiary hydroxyl function in the enantioselectively generated C-20' progenitor 39.
• KUEHNE, MARTIN E.;MATSON, PATRICIA A.;BORNMANN, WILLIAM G., J. ORG. CHEM., 56,(1991) N, C. 513-528
  作者：KUEHNE, MARTIN E.、MATSON, PATRICIA A.、BORNMANN, WILLIAM G.

  DOI：——

  日期：——
• Enantioselective syntheses of vinblastine, leurosidine, vincovaline and 20'-epi-vincovaline
  作者：Martin E. Kuehne、Patricia A. Matson、William G. Bornmann

  DOI：10.1021/jo00002a008

  日期：1991.1

  The binary indole-indoline alkaloids vinblastine (1), leurosidine (13), 20'-epi-vincovaline (14a), and vincovaline (14b) were obtained by coupling of vindoline (3) to the tetracyclic intermediates 7a, 7b or 22a, 22b, followed by reduction and cyclization steps (60% overall yield for these reactions). The intermediates were obtained by enantioselective establishment of C20' through a first-step Sharpless oxidation (10a,b) and followed by a subsequent diastereomeric separation (20a,b or 21a,b). Alternatively, enantioselective control of the key secodine-type cyclization in the reaction sequence provided the tetracyclic intermediates 54 and 60 for coupling to vindoline. Selective generation of the natural (1, 13, 14a,b) or unnatural (30, 34, 35a,b) atropisomeric forms of the alkaloids was achieved through alternative closures of ring D'. The natural products were also obtained from the higher energy atropisomers by conformational inversion on heating. For the vinblastine synthesis, the overall yield was 22%.