2-C-(Hydroxymethyl)-4,5-O-isopropylidene-3-O-(p-methoxybenzyl)-D-arabinose diethyl acetal | 171625-62-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-C-(Hydroxymethyl)-4,5-O-isopropylidene-3-O-(p-methoxybenzyl)-D-arabinose diethyl acetal
• 英文别名: (2S,3R)-2-(Diethoxymethyl)-3-((R)-2,2-dimethyl-1,3-dioxolan-4-YL)-3-(4-methoxybenzyloxy)propane-1,2-diol；(2S,3R)-2-(diethoxymethyl)-3-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-3-[(4-methoxyphenyl)methoxy]propane-1,2-diol
• CAS: 171625-62-0
• 化学式: C₂₁H₃₄O₈
• 分子量: 414.496
• InChiKey: GXPITZBRJHUCDS-OPYAIIAOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  29
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  95.8
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-C-(Hydroxymethyl)-4,5-O-isopropylidene-3-O-(p-methoxybenzyl)-D-arabinose diethyl acetal 在 咪唑 、 碘 、 sodium hexamethyldisilazane 、 4-甲基苯磺酸吡啶 、 sodium hydride 、 三苯基膦 、 锌 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 8.0h， 生成 (1Z,3S,4R)-2-(benzyloxy)-1-iodo-4-<(p-methoxybenzyl)oxy>-3-<<(p-methoxybenzyl)oxy>methyl>-1,5-hexadiene
  参考文献：
  名称：

  Stereochemical Models for the Enantiocontrolled Construction of Fully Functionalized C Rings via Intramolecular Aldolization in Advanced Precursors to Paclitaxel

  摘要：

  Six transition-state models for intramolecular aldol C-ring annulation in suitably substituted bicyclo-[6.2.1]undecanones have been defined. The first consideration is the inherent conformational flexibility of the nine-membered ketonic ring which does not limit effective deprotonation to a single C-8 epimer. When the oxygen substituents at C-4 and C-5 are not covalently linked, the configuration at C-5 defines the stereochemical course of the ring closure, with only the beta series being amenable to the proper elaboration of paclitaxel. When C-4 and C-5 are incorporated into a 1,3-dioxane ring instead, the principal stereocontrol element is translocated into the aryl-substituted carbon of the cyclic acetal. To the extent that the Ar group remains equatorially disposed, then proper aldolization will materialize in only one of the four possible diastereomers. Experimental tests that are provided for three of the models are shown to conform to expectations. This analysis of the origin of stereoselectivity has, for the first time, defined the scope and limitations associated with C-ring closure by means of the aldol protocol.

  DOI：

  10.1021/jo981749j
• 作为产物：
  描述：

  2-desoxy-4,5-isopropylidene-2-C-methylene-D-pentose 在 叔丁基过氧化氢 、 sodium hydroxide 、 vanadyl acetylacetonate 、 sodium hydride 作用下， 以 二氯甲烷 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 18.0h， 生成 2-C-(Hydroxymethyl)-4,5-O-isopropylidene-3-O-(p-methoxybenzyl)-D-arabinose diethyl acetal
  参考文献：
  名称：

  An Abbreviated, Highly Stereocontrolled Route to Precursors of Taxol. Elaboration of a Fully Functionalized C Ring by Means of Intramolecular Aldol Cyclization

  摘要：

  The asymmetric synthesis of an advanced taxol precursor is reported. The scheme involves the conversion of (R)-glyceraldehyde acetonide into the Q-vinyl iodide 2, transmetalation of this intermediate, and 1,2-addition to the D-camphor derivative 11 from the endo direction. This convergent coupling gives rise to exo alcohol 12, which undergoes anionic oxy-Cope rearrangement at low temperatures. In situ methylation of the resulting enolate anion delivers 13, which is chemoselectively transformed into aldehyde 18. In a key step, the aldol cyclization of 18 proceeds without beta-elimination to deliver a tricyclic product in which proper absolute configuration is adopted at the two stereogenic centers being newly introduced. Following protection of the hydroxyl substituent as in 19b,the alpha-hydroxy ketone 21 is heated with aluminum tri-tert-butoxide in benzene in order to effect near-quantitative rearrangement to the taxol-like isomer 22.

  DOI：

  10.1021/jo00129a027

文献信息

• An Abbreviated, Highly Stereocontrolled Route to Precursors of Taxol. Elaboration of a Fully Functionalized C Ring by Means of Intramolecular Aldol Cyclization
  作者：Leo A. Paquette、Francis J. Montgomery、Ting-Zhong Wang

  DOI：10.1021/jo00129a027

  日期：1995.12

  The asymmetric synthesis of an advanced taxol precursor is reported. The scheme involves the conversion of (R)-glyceraldehyde acetonide into the Q-vinyl iodide 2, transmetalation of this intermediate, and 1,2-addition to the D-camphor derivative 11 from the endo direction. This convergent coupling gives rise to exo alcohol 12, which undergoes anionic oxy-Cope rearrangement at low temperatures. In situ methylation of the resulting enolate anion delivers 13, which is chemoselectively transformed into aldehyde 18. In a key step, the aldol cyclization of 18 proceeds without beta-elimination to deliver a tricyclic product in which proper absolute configuration is adopted at the two stereogenic centers being newly introduced. Following protection of the hydroxyl substituent as in 19b,the alpha-hydroxy ketone 21 is heated with aluminum tri-tert-butoxide in benzene in order to effect near-quantitative rearrangement to the taxol-like isomer 22.
• Stereochemical Models for the Enantiocontrolled Construction of Fully Functionalized C Rings via Intramolecular Aldolization in Advanced Precursors to Paclitaxel
  作者：Leo A. Paquette、Qingbei Zeng、Hon-Chung Tsui、Jeffrey N. Johnston

  DOI：10.1021/jo981749j

  日期：1998.11.1

  Six transition-state models for intramolecular aldol C-ring annulation in suitably substituted bicyclo-[6.2.1]undecanones have been defined. The first consideration is the inherent conformational flexibility of the nine-membered ketonic ring which does not limit effective deprotonation to a single C-8 epimer. When the oxygen substituents at C-4 and C-5 are not covalently linked, the configuration at C-5 defines the stereochemical course of the ring closure, with only the beta series being amenable to the proper elaboration of paclitaxel. When C-4 and C-5 are incorporated into a 1,3-dioxane ring instead, the principal stereocontrol element is translocated into the aryl-substituted carbon of the cyclic acetal. To the extent that the Ar group remains equatorially disposed, then proper aldolization will materialize in only one of the four possible diastereomers. Experimental tests that are provided for three of the models are shown to conform to expectations. This analysis of the origin of stereoselectivity has, for the first time, defined the scope and limitations associated with C-ring closure by means of the aldol protocol.