Boc-D-isoleucinal | 141321-54-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Boc-D-isoleucinal
• 英文别名: (2R,3R)-N-Boc-D-isoleucinal；N-Boc-2(R),3(R)-3-methylpentanal；tert-butyl N-[(2R,3R)-3-methyl-1-oxopentan-2-yl]carbamate
• CAS: 141321-54-2
• 化学式: C₁₁H₂₁NO₃
• 分子量: 215.293
• InChiKey: YJAAJMSZVZJPOQ-BDAKNGLRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Boc-D-isoleucinal 在 吡啶 、 三乙胺 、 三氟乙酸 、 lithium diisopropyl amide 作用下， 以 二氯甲烷 为溶剂， 反应 24.92h， 生成 [(2R,3R)-2-[(2R)-butan-2-yl]-5-oxopyrrolidin-3-yl] acetate
  参考文献：
  名称：

  Synthesis and properties of the eight isostatine stereoisomers

  摘要：

  The eight possible stereoisomers of isostatine, (3S,4R,5S)-4-amino-3-hydroxy-5-methylheptanoic acid, have been synthesized from the four isomeric D- and L-isoleucinals and D- and L-allo-isoleucinals and ethyl lithioacetate. The eight isomers have been compared for the GC retention times of their bis(trifluoroacetyl) methyl ester derivatives and the H-1 NMR properties of the gamma-lactams derived from them. The natural isomer was shown to be the 3S,4R,5S isomer.

  DOI：

  10.1021/jo00037a012
• 作为产物：
  描述：

  Boc-D-异亮氨酸 在 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 Boc-D-isoleucinal
  参考文献：
  名称：

  Deglycobleomycin A6 analogues modified in the methylvalerate moiety

  摘要：

  Previous studies have indicated that the methylvalerate subunit of bleomycin (BLM) plays an important role in facilitating DNA cleavage by BLM and deglycoBLM. Eleven methylvalerate analogues have been synthesized and incorporated into deglycoBLM congeners by the use of solid-phase synthesis. The effect of the valerate moiety in the deglycoBLM analogues has been studied by comparison with the parent deglycoBLM A(5) using supercoiled DNA relaxation and sequence-selective DNA cleavage assays. All of the deglycoBLM analogues were found to effect the relaxation of the plasmid DNA. Those analogues having aromatic C4-substituents exhibited cleavage efficiency comparable to that of deglycoBLM A(5). Some, but not all, of the deglycoBLM analogues were also capable of mediating sequence-selective DNA cleavage. (C) 2011 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2011.04.047

文献信息

• Total synthesis of spiruchostatin B, a potent histone deacetylase inhibitor, from a microorganism
  作者：Toshiya Takizawa、Kazuhiro Watanabe、Koichi Narita、Takamasa Oguchi、Hideki Abe、Tadashi Katoh

  DOI：10.1039/b718310k

  日期：——

  The first total synthesis of spiruchostatin B, a potent histone deacetylase inhibitor, was achieved in a convergent manner; the synthesis established stereochemistry at the C5'' position.

  一种有效的组蛋白脱乙酰基酶抑制剂spiruchostatin B的第一个全合成以收敛的方式得以实现。合成在C5''位置建立了立体化学。
• Total Synthesis of the Bicyclic Depsipeptide HDAC Inhibitors Spiruchostatins A and B, 5′′-<i>epi</i>-Spiruchostatin B, FK228 (FR901228) and Preliminary Evaluation of Their Biological Activity
  作者：Koichi Narita、Takuya Kikuchi、Kazuhiro Watanabe、Toshiya Takizawa、Takamasa Oguchi、Kyosuke Kudo、Keisuke Matsuhara、Hideki Abe、Takao Yamori、Minoru Yoshida、Tadashi Katoh

  DOI：10.1002/chem.200901552

  日期：2009.10.26

  Julia–Kocienski olefination of a 1,3‐propanediol‐derived sulfone and a L‐ or D‐malic acid‐derived aldehyde to access the most synthetically challenging unit, (3S or 3R,4E)‐3‐hydroxy‐7‐mercaptohept‐4‐enoic acid, present in a D‐alanine‐ or D‐valine‐containing segment; ii) a condensation of a D‐valine‐D‐cysteine‐ or D‐allo‐isoleucine‐D‐cysteine‐containing segment with a D‐alanine‐ or D‐valine‐containing

  双环去肽肽组蛋白去乙酰化酶（HDAC）抑制剂spiruchostatins A和B，5'′- epi- spiruchostatin B和FK228可以通过聚合和统一的方式高效合成。合成方法涉及以下关键步骤：i）1，3-丙二醇衍生的砜和L-或D-苹果酸衍生的醛的Julia-Kocienski烯化反应，以合成最具挑战性的单元（3 S或3 R，4 E）-3-羟基-7-巯基庚基-4-烯酸，存在于含有D-丙氨酸或D-缬氨酸的链段中；ii）D-缬氨酸-D-半胱氨酸-或D的缩合-同种异体-isoleucine- d -半胱氨酸含与段d -alanine-或d含缬氨酸段直接组装相应的开环-acids; 和iii）的大环化开环使用椎名法或光延法构造必需15-或16-元大环内酯-酸。本合成已建立了螺旋藻抑素B的C5'立体化学。此外，对合成的二肽的HDAC抑制测定和细胞生长抑制分析确定了其效力的顺序，并揭示了
• [EN] THIOUREA DERIVATIVES OR NON-TOXIC SALTS THEREOF FOR INHIBITNG RAS-TRANSFORMED CELL GROWTH<br/>[FR] DERIVES DE THIO-UREE ET SELS NON TOXIQUES DE CES DERIVES PERMETTANT D'INHIBER LA CROISSANCE CELLULAIRE TRANSFORMEE PAR "RAS"
  申请人：YUHAN CORPORATION

  公开号：WO1999012912A1

  公开（公告）日：1999-03-18

  (EN) The present invention relates to novel thiourea derivatives of formula (I) which possess an excellent activity for inhibiting ras-transformed cell growth, pharmaceutically acceptable salt or stereoisomer thereof, wherein R1 represents hydrogen; straight-chain or branched C1-C8-alkyl which is optionally substituted by substituents selected from a group consisting of halogen, C1-C6-alkoxy, C1-C6-alkoxycarbonyl and di(C1-C4-alkyl)amino; C2-C6-alkenyl; C1-C4-alkoxycarbonyl; C3-C6-cycloalkyl; phenyl which is optionally mono- to trisubstituted by substituents selected from a group consisting of halogen, C1-C6-alkyl, C1-C6-alkoxy, C1-C6-alkylthio, halogeno-C1-C6-alkyl, azido, nitro, amino, phenyl, di(C1-C4-alkyl)amino and hydroxy; phenyl-C1-C4-alkyl; naphthyl which is optionally substituted by di(C1-C4-alkyl)amino; benzoyl; pyridyl which is optinally substituted by substituents selected from a group consisting of halogen and C1-C6-alkoxy; or adamantyl; R2 and R3 independently of one another represent hydrogen, straight-chain or branched C1-C6-alkyl, C3-C6-cycloalkyl or benzyloxybenzyl; R4 represents C1-C4-alkyl substituted by phenyl wherein the phenyl moiety is optionally mono- to trisubstituted by substituents selected from a group consisting of halogen, halogeno-C1-C4-alkyl, C1-C4-alkylenedioxy, C1-C6-alkyl, nitro, C1-C6-alkoxy, carboxyl and C1-C6-alkoxycarbonyl; naphthyl-C1-C4-alkyl; thiophenyl-C1-C4-alkyl; C1-C6-alkyl which is optionally substituted by substituents selected from a group consisting of pyridyl, oxypyridyl, C1-C6-alkoxy and C1-C6-alkylthio; or C2-C6-alkynyl; and X represents nitro or cyano. The present invention also relates to a process for the preparation of the thiourea derivatives and a pharmaceutical composition for inhibition of ras-transformed cell growth comprising the same as an active ingredient.(FR) La présente invention se rapporte à de nouveaux dérivés de thio-urée représentés par la formule (I), qui s'avèrent très actifs s'agissant d'inhiber la croissance cellulaire transformée par la protéine 'ras', ainsi qu'aux sels pharmaceutiquement acceptables ou aux stéréoisomères de ces composés. Dans la formule (I), R1 représente l'hydrogène, un alkyle C1-C8 qui est éventuellement substitué par des substituants sélectionnés dans un groupe constitué par un halogène, alcoxy C1-C6, alcoxycarbonyle C1-C6 et amino di(alkyle C1-C4); alcényle C2-C6; alcoxycarbonyle C1-C4; cycloalkyle C3-C6; phényle qui est éventuellement mono- à tri-substitué par des substituants sélectionnés dans un groupe constitué par un halogène, alkyle C1-C6, alcoxy C1-C6, alkylthio C1-C6, halogéno-alkyle C1-C6, azido, nitro, amino, phényle, amino di(alkyle C1-C4) et hydroxy; phényl-alkyle C1-C4; naphtyle qui est éventuellement substitué par amino di(alkyle C1-C4); benzolyle; pyridyle qui est éventuellement substitué par des substituants sélectionnés dans un groupe constitué par un halogène et alcoxy C1-C6; ou adamantyle. Dans la formule (I) également, R2 et R3 représentent, indépendamment l'un de l'autre, l'hydrogène, un alkyle C1-C6 à chaîne linéaire ou ramifiée, alkyle C1-C6, cycloalkyle C3-C6 ou benzyloxybenzyle; R4 représente alkyle C1-C4 substitué par phényle, ladite fraction phényle étant éventuellement mono- à tri-substituée par des substituants sélectionnés dans un groupe constitué par un halogène, halogéno-alkyle C1-C4, alkylènedioxy C1-C4, alkyle C1-C6, nitro, alcoxy C1-C6, carboxyle et alcoxycarbonyle C1-C6; naphtyl-alkyle C1-C6; thiophényl-alkyle C1-C4; alkyle C1-C6 qui est éventuellement substitué par des substituants sélectionnés dans un groupe constitué par pyridyle, oxypyridyle, alcoxy C1-C6 et alkylthio C1-C6 ou alkynyle C2-C6; et X représente un nitro ou cyano. La présente invention se rapporte à un procédé de préparation de ces dérivés de thio-urée et à une composition pharmaceutique permettant d'inhiber la croissance cellulaire transformée par la protéine 'ras' et contenant ces dérivés en tant que principe actif.
• Synthesis and properties of the eight isostatine stereoisomers
  作者：Kenneth L. Rinehart、Ryuichi Sakai、Vimal Kishore、David W. Sullins、Kai Ming Li

  DOI：10.1021/jo00037a012

  日期：1992.5

  The eight possible stereoisomers of isostatine, (3S,4R,5S)-4-amino-3-hydroxy-5-methylheptanoic acid, have been synthesized from the four isomeric D- and L-isoleucinals and D- and L-allo-isoleucinals and ethyl lithioacetate. The eight isomers have been compared for the GC retention times of their bis(trifluoroacetyl) methyl ester derivatives and the H-1 NMR properties of the gamma-lactams derived from them. The natural isomer was shown to be the 3S,4R,5S isomer.
• Deglycobleomycin A6 analogues modified in the methylvalerate moiety
  作者：Xiaoqing Cai、Paul A. Zaleski、Ali Cagir、Sidney M. Hecht

  DOI：10.1016/j.bmc.2011.04.047

  日期：2011.6

  Previous studies have indicated that the methylvalerate subunit of bleomycin (BLM) plays an important role in facilitating DNA cleavage by BLM and deglycoBLM. Eleven methylvalerate analogues have been synthesized and incorporated into deglycoBLM congeners by the use of solid-phase synthesis. The effect of the valerate moiety in the deglycoBLM analogues has been studied by comparison with the parent deglycoBLM A(5) using supercoiled DNA relaxation and sequence-selective DNA cleavage assays. All of the deglycoBLM analogues were found to effect the relaxation of the plasmid DNA. Those analogues having aromatic C4-substituents exhibited cleavage efficiency comparable to that of deglycoBLM A(5). Some, but not all, of the deglycoBLM analogues were also capable of mediating sequence-selective DNA cleavage. (C) 2011 Published by Elsevier Ltd.