benzyl (2S)-2-((2R)-3-tert-butoxycarbonylamino-2-methylpropionyloxy)-4-methylpentanoate | 245125-88-6

• 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: benzyl (2S)-2-((2R)-3-tert-butoxycarbonylamino-2-methylpropionyloxy)-4-methylpentanoate
• 英文别名: (2S,2'R)-benzyl 2-[(3'-{[(tert-butoxy)carbonyl]amino}-2'-methylpropinoyl)oxy]-4-methylpentanoate；Boc-bAib(R)-OLeu-OBn；benzyl (2S)-4-methyl-2-[(2R)-2-methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]oxypentanoate
• CAS: 245125-88-6
• 化学式: C₂₂H₃₃NO₆
• 分子量: 407.507
• InChiKey: WUQGYAJBZVEOAX-AEFFLSMTSA-N

物化性质

• 沸点：
  509.3±35.0 °C(Predicted)
• 密度：
  1.090±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  29
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  90.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  benzyl (2S)-2-((2R)-3-tert-butoxycarbonylamino-2-methylpropionyloxy)-4-methylpentanoate 在 palladium hydroxide - carbon 4-二甲氨基吡啶 、 1-[3-(diethylamino)propyl]-3-ethylcarbodiimide hydrochloride 、 叠氮磷酸二苯酯 、 氢气 、 二甲基二环氧乙烷 、 碳酸氢钠 、 1-羟基苯并三唑 、 三乙胺 、 三氟乙酸 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 93.0h， 生成 2-{[{2-[(4-硝基苯基)磺酰]肼基<联氨基>}(羰基)乙酰基]氨基}苯甲酸
  参考文献：
  名称：

  Total Synthesis of Cryptophycins-1, -3, -4, -24 (Arenastatin A), and -29, Cytotoxic Depsipeptides from Cyanobacteria of the Nostocaceae

  摘要：

  A convergent synthesis of cryptophycins has been developed in which (5S,GR)-5-hydroxy-6-methyl-8-phenylocta-2(E),7(E)-dienoic add (A) is coupled with an amino acid. segment (B). Two stereoselective routes to A are described, the first employing allylation of an alpha-homochiral aldehyde and the second using asymmetric crotylation of an achiral aldehyde to establish the two stereogenic centers present in a. The styryl moiety of A was attached either via Stille coupling or through a Wadsworth-Emmons condensation with diethyl benzylphosphonate. The amino acid subunit B was prepared from benzyl (2S)-2-hydroxyisocaproate by connection first to N-Boc-beta-alanine or its (2R)-methyl-substituted derivative and then to (2R)-N-Boc-O-methyltyrosine or its nt-chloro derivative. Fusion of the A and B subunits was accomplished by initial esterification of the former with the latter, followed by macrocyclization using diphenyl phosphorazidate. In this way, cryptophycin-3, -4, and -29 were obtained along with the nonnatural cyclic depsipeptide 52. Epoxidation of cryptophycin-3 with dimethyldioxirane gave cryptophycin-1; analogous epoxidation of 52 afforded arenastatin A (cryptophycin-24).

  DOI：

  10.1021/jo9907585
• 作为产物：
  描述：

  L-alpha-羟基异己酸 在 4-二甲氨基吡啶 、 四丁基碘化铵 、 potassium carbonate 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 benzyl (2S)-2-((2R)-3-tert-butoxycarbonylamino-2-methylpropionyloxy)-4-methylpentanoate
  参考文献：
  名称：

  多功能化学酶合成方法，用于发现强隐藻霉素类似物。

  摘要：

  隐藻霉素是大环二肽天然产物的家族，对抗药性癌症显示出异常有效的抗增殖活性。复杂分子的合成和衍生化所面临的独特挑战促使我们研究化学酶法合成方法，该方法旨在获得用于生物学评估的新类似物。隐藻霉素硫酯酶（CrpTE）和隐霉素环氧化酶（CrpE）是一组通用的酶，可催化20多种天然隐藻毒素代谢产物的大环化和环氧化。因此，我们设想了一种药物开发策略，其中涉及将它们用作生产非天然衍生物的独立生物催化剂。在这里 我们开发了12种新的ABCD线性链伸长中间体的可扩展合成方法，该中间体包含杂环芳族基团作为天然A苄基的替代品。使用野生型CrpTE评估了每种中间体的N-乙酰半胱胺活化形式向大环产物的转化，这证明了该酶的出色灵活性。进行了半制备规模的反应，用于新隐藻霉素的分离和结构表征。然后评估每种化合物作为CrpE P450的底物，以及它们从这些底物生成环氧化产物的能力，这些底物在单元A苯乙烯基双键位置具有改变的

  DOI：

  10.1021/acschembio.9b00998

文献信息

• Efficient and Versatile Stereoselective Synthesis of Cryptophycins
  作者：Christian Alexander Mast、Stefan Eißler、Arvydas Stončius、Hans-Georg Stammler、Beate Neumann、Norbert Sewald

  DOI：10.1002/chem.200500282

  日期：2005.8.5

  units A to D which correspond to the respective amino acids and hydroxy acids. A new synthetic route to unit A allows the selective generation of all four stereogenic centres by introducing two of them in a catalytic asymmetric dihydroxylation, followed by substrate-controlled diastereoselective reactions. The diol also serves as the epoxide precursor. This approach provides selective access to stereoisomers

  隐藻霉素是具有四个逆合成单元A至D的环状双缩肽家族，其分别对应于氨基酸和羟基酸。一条新的合成路线通往A单元，通过在催化不对称二羟基化反应中引入两个立体异构中心，然后进行底物控制的非对映选择性反应，可以选择性生成所有四个立体异构中心。二醇还用作环氧化物前体。这种方法提供了对单元A的立体异构体（对映异构体，差向异构体）的选择性访问，以进行结构-活性关系研究。将单位A衍生物掺入隐藻素-1，隐藻素52和新型隐藻素差向异构体52中。
• Asymmetric Syntheses of Potent Antitumor Macrolides Cryptophycin B and Arenastatin A
  作者：Arun K. Ghosh、Alexander Bischoff

  DOI：10.1002/ejoc.200300814

  日期：2004.5

  Efficient and highly stereoselective syntheses of cryptophycin B and arenastatin A, potent cytotoxic agents, are described. An ester-derived titanium enolate mediated syn-aldol reaction was employed to generate the stereocenters C-5 and C-6. The route is convergent and provides a convenient access to the synthesis of structural variants of cryptophycins as well as members of its family.

  描述了有效的细胞毒剂隐藻素 B 和阿那他丁 A 的高效且高度立体选择性的合成。采用酯衍生的钛烯醇化物介导的顺醛醇反应来生成立体中心C-5和C-6。该路线是收敛的，为合成隐藻素及其家族成员的结构变体提供了方便的途径。
• A Convergent Synthesis of (+)-Cryptophycin B, a Potent Antitumor Macrolide from <i>Nostoc</i> sp. Cyanobacteria
  作者：Arun K. Ghosh、Alexander Bischoff

  DOI：10.1021/ol000058i

  日期：2000.6.1

  text] An efficient and highly stereoselective synthesis of cryptophycin B (2), a potent cytotoxic agent, is described. The ester-derived titanium-enolate-mediated syn-aldol reaction was employed to generate the stereocenters C(5) and C(6). The route is convergent and provides a convenient access to the synthesis of structural variants of cryptophycin B as well as members of its family.

  [结构-见正文]描述了一种有效的高度立体选择性的隐藻霉素B（2）（一种有效的细胞毒剂）合成方法。酯衍生的钛烯醇盐介导的顺式羟醛反应被用于生成立体中心C（5）和C（6）。该途径是会聚的，为合成隐藻霉素B及其家族成员的结构变体提供了便利。
• A Versatile Chemoenzymatic Synthesis for the Discovery of Potent Cryptophycin Analogs
  作者：Jennifer J. Schmidt、Yogan Khatri、Scott I. Brody、Catherine Zhu、Halina Pietraszkiewicz、Frederick A. Valeriote、David H. Sherman

  DOI：10.1021/acschembio.9b00998

  日期：2020.2.21

  demonstrated the exceptional flexibility of this enzyme. Semipreparative scale reactions were conducted for isolation and structural characterization of new cryptophycins. Each was then evaluated as a substrate for CrpE P450 and its ability to generate the epoxidized products from these substrates that possess altered electronics at the unit A styrenyl double bond position. Finally, biological evaluation of

  隐藻霉素是大环二肽天然产物的家族，对抗药性癌症显示出异常有效的抗增殖活性。复杂分子的合成和衍生化所面临的独特挑战促使我们研究化学酶法合成方法，该方法旨在获得用于生物学评估的新类似物。隐藻霉素硫酯酶（CrpTE）和隐霉素环氧化酶（CrpE）是一组通用的酶，可催化20多种天然隐藻毒素代谢产物的大环化和环氧化。因此，我们设想了一种药物开发策略，其中涉及将它们用作生产非天然衍生物的独立生物催化剂。在这里 我们开发了12种新的ABCD线性链伸长中间体的可扩展合成方法，该中间体包含杂环芳族基团作为天然A苄基的替代品。使用野生型CrpTE评估了每种中间体的N-乙酰半胱胺活化形式向大环产物的转化，这证明了该酶的出色灵活性。进行了半制备规模的反应，用于新隐藻霉素的分离和结构表征。然后评估每种化合物作为CrpE P450的底物，以及它们从这些底物生成环氧化产物的能力，这些底物在单元A苯乙烯基双键位置具有改变的
• Total Synthesis of Cryptophycins-1, -3, -4, -24 (Arenastatin A), and -29, Cytotoxic Depsipeptides from Cyanobacteria of the Nostocaceae
  作者：James D. White、Jian Hong、Lonnie A. Robarge

  DOI：10.1021/jo9907585

  日期：1999.8.1

  A convergent synthesis of cryptophycins has been developed in which (5S,GR)-5-hydroxy-6-methyl-8-phenylocta-2(E),7(E)-dienoic add (A) is coupled with an amino acid. segment (B). Two stereoselective routes to A are described, the first employing allylation of an alpha-homochiral aldehyde and the second using asymmetric crotylation of an achiral aldehyde to establish the two stereogenic centers present in a. The styryl moiety of A was attached either via Stille coupling or through a Wadsworth-Emmons condensation with diethyl benzylphosphonate. The amino acid subunit B was prepared from benzyl (2S)-2-hydroxyisocaproate by connection first to N-Boc-beta-alanine or its (2R)-methyl-substituted derivative and then to (2R)-N-Boc-O-methyltyrosine or its nt-chloro derivative. Fusion of the A and B subunits was accomplished by initial esterification of the former with the latter, followed by macrocyclization using diphenyl phosphorazidate. In this way, cryptophycin-3, -4, and -29 were obtained along with the nonnatural cyclic depsipeptide 52. Epoxidation of cryptophycin-3 with dimethyldioxirane gave cryptophycin-1; analogous epoxidation of 52 afforded arenastatin A (cryptophycin-24).