(S)-3-<(2S,3S,4R)-4--3-hydroxy-2-methylpentanoyl>-4-isopropyl-1,3-oxazolidin-2-one | 96443-48-0

• 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: (S)-3-<(2S,3S,4R)-4--3-hydroxy-2-methylpentanoyl>-4-isopropyl-1,3-oxazolidin-2-one
• 英文别名: (4S,2'S,3'S,4'R)-3-<4'-(N-((tert-butyloxy)carbonyl)amino)-3'-hydroxy-2'-methylpentanoyl>-4-isopropyl-2-oxazolidinone；(1R,2S,3S,4'S)-[2-hydroxy-4-(4'-isopropyl-2'-oxo-oxazolidin-3'-yl)-1,3-dimethyl-4-oxobutyl]carbamic acid tert-butyl ester；tert-butyl N-[(2R,3S,4S)-3-hydroxy-4-methyl-5-oxo-5-[(4S)-2-oxo-4-propan-2-yl-1,3-oxazolidin-3-yl]pentan-2-yl]carbamate
• CAS: 96443-48-0
• 化学式: C₁₇H₃₀N₂O₆
• 分子量: 358.435
• InChiKey: LVQSYRHUOVLBJG-LOWDOPEQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-3-<(2S,3S,4R)-4--3-hydroxy-2-methylpentanoyl>-4-isopropyl-1,3-oxazolidin-2-one 在 lithium hydroxide 、 二甲基硫 、 双氧水 、 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 (2S,3S,4R)-4-amino-3-hydroxy-2-methylpentanoic acid
  参考文献：
  名称：

  博莱霉素类抗生素的固相合成。108 人去糖霉素文库的构建

  摘要：

  博来霉素 (BLM) 是从轮状链霉菌中分离出的结构相关的糖肽抗生素，可介导 DNA 和 RNA 的序列选择性氧化损伤。去糖博来霉素缺乏碳水化合物部分，可以像博来霉素本身一样切割 DNA，尽管效力较低，并且已成功用于分析博来霉素的功能域。尽管已经报道了对博来霉素和去甘博来霉素的结构修饰，但尚未描述具有增强的 DNA 切割活性的博来霉素或去甘博来霉素类似物。在固体支持物上成功合成了去甘博莱霉素，允许通过平行固相合成轻松固相合成 108 种独特的去甘博莱霉素类似物。每种去糖博莱霉素类似物都被有效合成；通过HPLC积分确定每种粗产物的纯度大于60%。去糖博莱霉素库的固相合成提供了接近毫克到毫克的每种去糖博莱霉素，从而允许通过 (1) H NMR 和高分辨率质谱法进行表征。每个类似物都表现出高于背景切割的超螺旋质粒 DNA 松弛；该文库包括两种类似物，它们比亲本去糖霉素分子在更大程度上介导质粒松弛。

  DOI：

  10.1021/ja021388w
• 作为产物：
  描述：

  (R)-1-(甲氧基(甲基)氨基)-1-氧代-2-丙基氨基甲酸叔丁酯 在 lithium aluminium tetrahydride 、 三氟甲磺酸二丁硼 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (S)-3-<(2S,3S,4R)-4--3-hydroxy-2-methylpentanoyl>-4-isopropyl-1,3-oxazolidin-2-one
  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

• On the reversal of the stereoselectivity in the evans aldol reaction of α-amino aldehydes
  作者：Kyoko Hayashi、Yasumasa Hamada、Takayuki Shioiri

  DOI：10.1016/0040-4039(91)80500-6

  日期：1991.12

  Reversal of the stereoselectivity in the Evans aldol reaction of Boc-(S)-prolinal (3), observed during the total synthesis of dolastatin 10 (1), was proved to be due to the amounts of dibutylboron triflate and triethylamine. (R)-Alaninal derivatives (14) also showed the analogous reversal of the stereoselectivity.

  在全合成dolastatin 10（1）期间观察到的Boc-（S）-脯氨酸（3）的Evans aldol反应中的立体选择性逆转被证明是由于三氟甲磺酸二丁基硼和三乙胺的含量所致。（R）-丙氨酸衍生物（14）也显示出立体选择性的类似逆转。
• Solid-Phase Synthesis of Bleomycin Group Antibiotics. Construction of a 108-Member Deglycobleomycin Library
  作者：Christopher J. Leitheiser、Kenneth L. Smith、Michael J. Rishel、Shigeki Hashimoto、Kazuhide Konishi、Craig J. Thomas、Chunhong Li、Michael M. McCormick、Sidney M. Hecht

  DOI：10.1021/ja021388w

  日期：2003.7.1

  structural modifications to bleomycin and deglycobleomycin have been reported, no bleomycin or deglycobleomycin analogue having enhanced DNA cleavage activity has yet been described. The successful synthesis of a deglycobleomycin on a solid support has permitted the facile solid-phase synthesis of 108 unique deglycobleomycin analogues through parallel solid-phase synthesis. Each of the deglycobleomycin analogues

  博来霉素 (BLM) 是从轮状链霉菌中分离出的结构相关的糖肽抗生素，可介导 DNA 和 RNA 的序列选择性氧化损伤。去糖博来霉素缺乏碳水化合物部分，可以像博来霉素本身一样切割 DNA，尽管效力较低，并且已成功用于分析博来霉素的功能域。尽管已经报道了对博来霉素和去甘博来霉素的结构修饰，但尚未描述具有增强的 DNA 切割活性的博来霉素或去甘博来霉素类似物。在固体支持物上成功合成了去甘博莱霉素，允许通过平行固相合成轻松固相合成 108 种独特的去甘博莱霉素类似物。每种去糖博莱霉素类似物都被有效合成；通过HPLC积分确定每种粗产物的纯度大于60%。去糖博莱霉素库的固相合成提供了接近毫克到毫克的每种去糖博莱霉素，从而允许通过 (1) H NMR 和高分辨率质谱法进行表征。每个类似物都表现出高于背景切割的超螺旋质粒 DNA 松弛；该文库包括两种类似物，它们比亲本去糖霉素分子在更大程度上介导质粒松弛。
• Man-designed bleomycins: Significance of the binding sites as enzyme models and of the stereochemistry of the linker moiety
  作者：Takashi Owa、Andreas Haupt、Masami Otsuka、Susumu Kobayashi、Nobuo Tomioka、Akiko Itai、Masaji Ohno、Takashi Shiraki、Motonari Uesugi、Yukio Sugiura、Kenji Maeda

  DOI：10.1016/s0040-4020(01)90783-5

  日期：1992.1

  Comparison of the DNA cleavage activity of man-designed bleomycins demonstrates that belomycins are small enzymes comprised of a catalytic site and a binding site. The linker moiety is shown to be significant for DNA binding, and inversion of its stereochemistry results in a dramatic decrease in the DNA-cleaving efficiency. One of the man-designed BLMs shows excellent cytotoxicity against L1210.

  人为设计的博来霉素的DNA切割活性的比较表明，博来霉素是由催化位点和结合位点组成的小酶。接头部分显示出对DNA结合的重要作用，其立体化学的反转导致DNA切割效率的显着降低。人为设计的BLM之一对L1210具有出色的细胞毒性。
• Total Synthesis of Bleomycin A2 and Related Agents. 1. Synthesis and DNA Binding Properties of the Extended C-Terminus: Tripeptide S, Tetrapeptide S, Pentapeptide S, and Related Agents
  作者：Dale L. Boger、Steven L. Colletti、Takeshi Honda、Royce F. Menezes

  DOI：10.1021/ja00092a011

  日期：1994.6

  Full details of concise, diastereocontrolled syntheses of 2-5 and their incorporation into tri-, tetra-, and pentapeptide S, the C-terminus of bleomycin Alt are described. The extension of the studies to the synthesis of a complete set of tri- and tetrapeptide S structural analogs 29a,b and 43b-j is detailed, and their DNA binding constants (apparent K-B, calf thymus DNA) and apparent binding site sizes were determined. Consistent with past observations, the studies highlight the fact that the majority of the DNA binding affinity for bleomycin A(2) (1.0 X 10(5) M(-1)) and deglycobleomycin Aa (1.1 x 10(5) M(-1)) is embodied within N-BOC-tripeptide S (0.26 X 10(5) M(-1)). The additional comparisons of 29a (O.18 x 10(5) M(-1)), N-BOC-tetrapeptide S (0.21 x 10(5) M(-1)), 43h (0.20 x 10(5) M(-1)), and N-BOC-pentapeptide S (0.23 X 10(5) M(-1)) versus N-BOC-dipeptide S (0.10 x 10(5) M(-1)) indicate productive stabilizing binding interactions for the tripeptide S L-threonine subunit and substituent, illustrate that the entire pentanoic acid subunit of tetrapeptide S and its substituents do not significantly contribute to DNA binding affinity, and indicate that the entire beta-hydroxy-L-histidine subunit of pentapeptide S does not contribute to DNA binding affinity. With the exception of the L-threonine side chain substituent, the observations suggest that the tri- and tetrapeptide S substituent effects on the bleomycin A(2) DNA cleavage reaction are not due to substantial stabilizing binding interactions with duplex DNA. In addition, the measured apparent binding site sizes for bleomycin A(2)(3.8 base pairs), deglycobleomycin A(2) (3.9 base pairs), N-BOC-tripeptide S (3.6 base pairs), N-BOC-tetrapeptide S (3.7 base pairs), 43h (3.5 base pairs), and N-BOC-pentapeptide S (4.2 base pairs) versus N-BOC-dipeptide S (2.2 base pairs) and 29a (2.7 base pairs) suggest that it is the tripeptide S subunit of bleomycin A(2) that is fully bound to duplex DNA, that the tripeptide S L-threonine hydroxyethyl substituent detectably affects the agent interaction with duplex DNA, but that the presence or absence of the other tetrapeptide S and pentapeptide S backbone substituents do not substantially alter the binding site size or tripeptide S binding mode.
• 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.