(6R)-N-<(2S)-2-<(Benzyloxy)methyl>pyrrolidino>-6-<(2-bromo-3,4-dimethoxybenzoyl)methyl>-2-piperidinone | 162756-00-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (6R)-N-<(2S)-2-<(Benzyloxy)methyl>pyrrolidino>-6-<(2-bromo-3,4-dimethoxybenzoyl)methyl>-2-piperidinone
• 英文别名: (6R)-6-[2-(2-bromo-4,5-dimethoxyphenyl)-2-oxoethyl]-1-[(2S)-2-(phenylmethoxymethyl)pyrrolidin-1-yl]piperidin-2-one
• CAS: 162756-00-5
• 化学式: C₂₇H₃₃BrN₂O₅
• 分子量: 545.473
• InChiKey: UYOYPEXBFXGTAM-RTWAWAEBSA-N

物化性质

• 沸点：
  633.5±65.0 °C(Predicted)
• 密度：
  1.319±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  68.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (6R)-N-<(2S)-2-<(Benzyloxy)methyl>pyrrolidino>-6-<(2-bromo-3,4-dimethoxybenzoyl)methyl>-2-piperidinone 在 氢氧化钾 、 sodium hydroxide 、 lithium aluminium tetrahydride 、 重铬酸吡啶 、 硼烷四氢呋喃络合物 、 偶氮二异丁腈 、 4 A molecular sieve 、 三正丁基氢锡 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 苯 为溶剂， 生成 小穗苎麻素
  参考文献：
  名称：

  （R）-（-）-隐尿嘧啶的对映选择性合成

  摘要：

  描述了基于高效的不对称酰胺基烷基化的天然（R）-（-）-隐氨氯林的对映选择性合成，其使用环状N-酰基亚胺中间体。

  DOI：

  10.1016/0040-4039(94)02376-m
• 作为产物：
  描述：

  1-(2-bromo-4,5-dimethoxyphenyl)ethanone 在 三氟化硼乙醚 、 lithium diisopropyl amide 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 (6R)-N-<(2S)-2-<(Benzyloxy)methyl>pyrrolidino>-6-<(2-bromo-3,4-dimethoxybenzoyl)methyl>-2-piperidinone
  参考文献：
  名称：

  Asymmetric Total Synthesis of (R)-(-)-Cryptopleurine and (R)-(-)-Julandine via Highly Enantioselective Amidoalkylations with N-Acylhydrazonium Salts

  摘要：

  The first enantioselective total syntheses of the phenanthroquinolizidine alkaloid(-)-cryptopleurine (1) and its seco base (-)-julandine [(R)-3] are described. The synthesis of(R)-3 allowed the 9aS configuration to be assigned to natural dextrorotatory julandine as shown by structure (S)-3. Both synthetic approaches are based on the high degree of 1,3-asymmetric induction achieved using an N-acylhydrazonium salt, which belongs to a new structural class of activated azomethines. Upon exposure of methoxy lactam 9, with a chiral 2-substituted pyrrolidine auxiliary, to BF3 . Et(2)O and a silyl enol ether the in situ generated N-acylhydrazonium intermediate 10 underwent asymmetric nucleophilic addition to give the (GR)-keto lactams 13 and 14 with complete diastereoselectivity. On the other hand, nucleophilic addition to the N-acylhydrazonium ion 25, with an acyclic chiral auxiliary, showed poor diastereoselectivity. From these results, the high degree of diastereoselection observed for the N-acylhydrazonium ion 10 can be rationalized in terms of the pyramidal stability of the trivalent nitrogen in the chiral pyrrolidine auxiliary. Removal of the chiral auxiliary from 13 and 14 was achieved by reductive N-N bond cleavage using BH3 . THF, affording (BS)-piperidine derivatives 15 and 31, respectively, which were transformed into quinolizidinones 30 and 35, respectively, via intramolecular aldol condensation. Reduction of 30 with alane provided (-)julandine [(R)-3]. In addition, 35 was converted to (-)-cryptopleurine (1) in two steps, by radical cyclization with Bu(3)SnH and AIBN, followed by LiAlH4 reduction.

  DOI：

  10.1021/jo00124a025

文献信息

• Enantioselective synthesis of (R)-(−)-Cryptopleurine
  作者：Hideaki Suzuki、Sakae Aoyagi、Chihiro Kibayashi

  DOI：10.1016/0040-4039(94)02376-m

  日期：1995.2

  An enantioselective synthesis of naturally occurring (R)-(−)-cryptopleurine based on highly efficient asymmetric amidoalkylation using a cyclic N-acyliminium intermediate is described.

  描述了基于高效的不对称酰胺基烷基化的天然（R）-（-）-隐氨氯林的对映选择性合成，其使用环状N-酰基亚胺中间体。
• Asymmetric Total Synthesis of (R)-(-)-Cryptopleurine and (R)-(-)-Julandine via Highly Enantioselective Amidoalkylations with N-Acylhydrazonium Salts
  作者：Hideaki Suzuki、Sakae Aoyagi、Chihiro Kibayashi

  DOI：10.1021/jo00124a025

  日期：1995.9

  The first enantioselective total syntheses of the phenanthroquinolizidine alkaloid(-)-cryptopleurine (1) and its seco base (-)-julandine [(R)-3] are described. The synthesis of(R)-3 allowed the 9aS configuration to be assigned to natural dextrorotatory julandine as shown by structure (S)-3. Both synthetic approaches are based on the high degree of 1,3-asymmetric induction achieved using an N-acylhydrazonium salt, which belongs to a new structural class of activated azomethines. Upon exposure of methoxy lactam 9, with a chiral 2-substituted pyrrolidine auxiliary, to BF3 . Et(2)O and a silyl enol ether the in situ generated N-acylhydrazonium intermediate 10 underwent asymmetric nucleophilic addition to give the (GR)-keto lactams 13 and 14 with complete diastereoselectivity. On the other hand, nucleophilic addition to the N-acylhydrazonium ion 25, with an acyclic chiral auxiliary, showed poor diastereoselectivity. From these results, the high degree of diastereoselection observed for the N-acylhydrazonium ion 10 can be rationalized in terms of the pyramidal stability of the trivalent nitrogen in the chiral pyrrolidine auxiliary. Removal of the chiral auxiliary from 13 and 14 was achieved by reductive N-N bond cleavage using BH3 . THF, affording (BS)-piperidine derivatives 15 and 31, respectively, which were transformed into quinolizidinones 30 and 35, respectively, via intramolecular aldol condensation. Reduction of 30 with alane provided (-)julandine [(R)-3]. In addition, 35 was converted to (-)-cryptopleurine (1) in two steps, by radical cyclization with Bu(3)SnH and AIBN, followed by LiAlH4 reduction.