cryptophycin-29

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: cryptophycin-29
• 英文别名: Cryptophycin 29；(3S,10R,13E,16S)-10-[(3-chloro-4-methoxyphenyl)methyl]-3-(2-methylpropyl)-16-[(E,2R)-4-phenylbut-3-en-2-yl]-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone
• 化学式: C₃₄H₄₁ClN₂O₇
• 分子量: 625.162
• InChiKey: XFXOMGLTDWTPTP-SEZBCZDQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  44
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  cryptophycin-29 在 Crp E epoxidase 、 Crp TE 、 spinach ferridoxin reductase 、 NADPH 、 氧气 作用下， 生成 cryptophycin-27
  参考文献：
  名称：

  Frontiers and Opportunities in Chemoenzymatic Synthesis

  摘要：

  Natural product biosynthetic pathways have evolved enzymes with myriad activities that represent an expansive array of chemical transformations for constructing secondary metabolites. Recently, harnessing the biosynthetic potential of these enzymes through chemoenzymatic synthesis has provided a powerful tool that often rivals the most sophisticated methodologies in modern synthetic chemistry and provides new opportunities for accessing chemical diversity. Herein, we describe our research efforts with enzymes from a broad collection of biosynthetic systems, highlighting recent progress in this exciting field.

  DOI：

  10.1021/jo101124n
• 作为产物：
  描述：

  (3S,4R)-1-[(tert-butyldimethylsilyl)oxy]-4-methylhex-5-en-3-ol 在 吡啶 、 咪唑 、 4-二甲氨基吡啶 、 正丁基锂 、 叠氮磷酸二苯酯 、 四丁基氟化铵 、 碳酸氢钠 、 戴斯-马丁氧化剂 、 氟化氢吡啶 、 臭氧 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 131.75h， 生成 cryptophycin-29
  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

文献信息

• Structure determination, conformational analysis, chemical stability studies, and antitumor evaluation of the cryptophycins. Isolation of 18 new analogs from Nostoc sp. strain GSV 224
  作者：Trimurtulu Golakoti、Junichi Ogino、Carl E. Heltzel、Trang Le Husebo、Craig M. Jensen、Linda K. Larsen、Gregory M. L. Patterson、Richard E. Moore、Susan L. Mooberry、Thomas H. Corbett、Frederick A. Valeriote

  DOI：10.1021/ja00154a002

  日期：1995.12.1

  Using a modified isolation procedure devoid of methanol, 18 new cyclic cryptophycins have been isolated from Nostoc sp. GSV 224 as minor constituents in addition to cryptophycins-1 (A), -2 (B), -3 (C), and -4 (D). Acyclic cryptophycins are not found, indicating that the previously reported cryptophycins-5 (E methyl ester), -6 (F methyl ester), and -7 (G) are artifacts produced as a consequence of using methanol in the isolation scheme. Seventeen of the new cyclic analogs differ in structure in either one of the two hydroxy acid units, viz. unit A [(5S,6S,7R,8R)-7,8-epoxy-5-hydroxy-6-methyl-8-phenyl-2(E)-octenoic acid for cryptophycin-1 or (5S,6S)-5-hydroxy-6-methyl-8-phenyl-2(E),7(E)-octadienoic acid for cryptophycin-3] and unit D [(2S)-2-hydroxy-4-methylvaleric acid], or one of the two amino acid units, viz. unit B [(2R)-2-amino-3-(3-chloro-4-methoxyphenyl)propionic acid] and unit C [(2R)3-amino-2-methylpropionic acid], found in the cyclic ABCD peptolide. In unit A of cryptophycins-26, -28, -30, and -40, the methyl group on C-6 is missing or the Delta(2)-double bond is hydrated. In unit B of cryptophycins-16, -17, -23, 31, -43, and -45, the aromatic ring is phenolic and/or possesses two or zero chlorines. In unit C of cryptophycins-21 and -29, the methyl group on C-2 is missing. In unit D of cryptophycins-18, -19, -49, -50, and -54, a different alkyl group (propyl, isopropyl, or sec-butyl) is attached to C-2. Only one of the new analogs, cryptophycin-24, differs in structure for two units by lacking chlorine in unit B and the methyl group in unit C. Revised structures are presented for cryptophycins-5, -6, and -7 and are correlated with cryptophycin-3, the relative stereochemistry of which has been further rigorously established by X-ray crystallography. NOE studies show that the preferred conformations of most cryptophycins in solution differ from the conformation of cryptophycin-3 in the crystal state. Although cryptophycin-1 is relatively stable at pH 7, both in ionic and nonionic media, the ester bond linking units C and D is fairly labile to solvolysis and mild base hydrolysis. Structure-activity relationship studies indicate that the intact macrolide ring, the epoxide group, the chloro and 0-methyl groups in unit B, and the methyl group in unit C are needed for the in vivo activity of cryptophycin-1.
• Enzymatic Release and Macrolactonization of Cryptophycins from a Safety-Catch Solid Support
  作者：Wolfgang Seufert、Zachary Q. Beck、David H. Sherman

  DOI：10.1002/anie.200703665

  日期：2007.12.10
• 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).
• Frontiers and Opportunities in Chemoenzymatic Synthesis
  作者：Jonathan D. Mortison、David H. Sherman

  DOI：10.1021/jo101124n

  日期：2010.11.5

  Natural product biosynthetic pathways have evolved enzymes with myriad activities that represent an expansive array of chemical transformations for constructing secondary metabolites. Recently, harnessing the biosynthetic potential of these enzymes through chemoenzymatic synthesis has provided a powerful tool that often rivals the most sophisticated methodologies in modern synthetic chemistry and provides new opportunities for accessing chemical diversity. Herein, we describe our research efforts with enzymes from a broad collection of biosynthetic systems, highlighting recent progress in this exciting field.