(S)-1-Amino-2-<(benzyloxy)methyl>pyrrolidine | 162755-96-6

• 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: (S)-1-Amino-2-<(benzyloxy)methyl>pyrrolidine
• 英文别名: (2S)-2-(phenylmethoxymethyl)pyrrolidin-1-amine
• CAS: 162755-96-6
• 化学式: C₁₂H₁₈N₂O
• 分子量: 206.288
• InChiKey: CDGZRHATABLGOH-LBPRGKRZSA-N

物化性质

• 沸点：
  314.7±17.0 °C(Predicted)
• 密度：
  1.074±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  38.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-1-Amino-2-<(benzyloxy)methyl>pyrrolidine 在 三氟化硼四氢呋喃络合物 、 三氟化硼乙醚 、 sodium acetate 、 4-甲基苯磺酸吡啶 、 乙酸酐 、 三乙基硼氢化锂 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 32.25h， 生成 (S)-2-(苄氧基甲基)吡咯烷
  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
• 作为产物：
  描述：

  [(2S)-1-亚硝基吡咯烷-2-基]甲醇 在 lithium aluminium tetrahydride 、 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-1-Amino-2-<(benzyloxy)methyl>pyrrolidine
  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

文献信息

• Indeno [1,2-c]pyrazol-4-ones and their uses
  申请人：——

  公开号：US20010027195A1

  公开（公告）日：2001-10-04

  The present invention relates to the synthesis of a new class of indeno[1,2-c]pyrazol-4-ones of formula (I): 1 that are potent inhibitors of the class of enzymes known as cyclin dependent kinases, which relate to the catalytic subunits cdk1-9 and their regulatory subunits know as cyclins A-H. This invention also provides a novel method of treating cancer or other proliferative diseases by administering a therapeutically effective amount of one of these compounds or a pharmaceutically acceptable salt form thereof. Alternatively, one can treat cancer or other proliferative diseases by administering a therapeutically effective combination of one of the compounds of the present invention and one or more other known anti-cancer or anti-proliferative agents.

  本发明涉及合成一种新类别的indeno[1,2-c]pyrazol-4-ones化合物，其化学式为(I):1，这些化合物是一类名为细胞周期依赖性激酶的酶的强效抑制剂，与催化亚基cdk1-9及其调节亚基cyclins A-H有关。本发明还提供了一种新颖的治疗癌症或其他增生性疾病的方法，即通过给予这些化合物中的一种或其药用可接受的盐形式的治疗有效剂量。另外，可以通过给予本发明化合物之一与一种或多种其他已知的抗癌或抗增生剂的治疗有效组合来治疗癌症或其他增生性疾病。
• Asymmetric synthesis of 1-substituted tetrahydroisoquinolines by nucleophilic addition to hydrazonium ions. Application to the enantioselective syntheses of (+)- and (−)-salsolidines and (−)-cryptostyline II
  作者：Hideaki Suzuki、Sakae Aoyagi、Chihiro Kibayashi

  DOI：10.1016/00404-0399(50)1358-o

  日期：1995.9

  hydride reagents to hydrazonium salts modified by optically active 2-substituted pyrrolidine auxiliaries leads to highly enantioselective synthesis of 1-substituted tetrahydroisoquinolines. This methodology was applied to asymmetric synthesis of the title isoquinoline alkaloids.

  将碳亲核试剂和金属氢化物试剂亲核加成到旋光的2-取代的吡咯烷助剂改性的盐中，会导致1-取代的四氢异喹啉的高度对映选择性的合成。该方法学用于标题异喹啉生物碱的不对称合成。
• 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。
• US6407103B2
  申请人：——

  公开号：US6407103B2

  公开（公告）日：2002-06-18
• 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.