pantothenic acid propyl thioester | 157825-81-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: pantothenic acid propyl thioester
• 英文别名: S-propyl 3-[[(2R)-2,4-dihydroxy-3,3-dimethylbutanoyl]amino]propanethioate
• CAS: 157825-81-5
• 化学式: C₁₂H₂₃NO₄S
• 分子量: 277.385
• InChiKey: ZOTXMKALHVKGON-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  18
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  pantothenic acid propyl thioester 在 吡啶 、 三甲基氯硅烷 、 lithium bromide 作用下， 生成 S-propyl 3-[(2R)-2-hydroxy-3,3-dimethyl-4-phosphonooxybutyrylamino]thiopropionate
  参考文献：
  名称：

  Synthesis of Novel Analogs of Acetyl Coenzyme A: Mimics of Enzyme Reaction Intermediates

  摘要：

  An improved method for the synthesis of analogs of coenzyme A (CoA) and its thioesters, which are modified in the thiol or thioester moiety, has been developed using a combination of chemical and enzymatic reactions, The enzymes catalyzing the last two steps of CoA biosynthesis were used to prepare a CoA analog (1c) in which an amide bond is replaced by a thioester bond and the thiol group is replaced by a methyl group. Reaction of 1c with a primary amine in aqueous solution results in aminolysis of the thioester linkage to form the desired CoA analog. Reaction with different amines permits the introduction of a variety of functional groups in place of the nor mal thiol or thioester group. This methodology has been used in the synthesis of five new analogs of acetyl-CoA in which the thioester sulfur is replaced by a methylene group and the acetyl group is replaced by carboxylate (14a), nitro (14b), carboxamide (14c), methyl sulfoxide (14d), and methyl sulfone (14e) groups. 14a-c were designed to mimic the possible enolate or enol intermediate in the reaction of citrate synthase and related enzymes. 14a and 14c are potent inhibitors of citrate synthase, with K-i values 1000- and 570-fold lower than the K-m for acetyl-CoA, respectively. CD titrations indicate that 14a and 14c have low affinity for citrate synthase in the absence of oxaloacetate, consistent with their recognition as enol or enolate analogs. 14b is a poor inhibitor of citrate synthase, with affinity slightly lower than that for acetyl-CoA. These results are consistent with generation of the enol form of acetyl-CoA as the nucleophilic intermediate in the reaction of citrate synthase. 14d and 14e were designed to mimic the tetrahedral intermediate or transition state in the reaction of chloramphenicol acetyltransferase and related acetyl-CoA-dependent acetyltransferases. Both compounds are poor inhibitors of chloramphenicol acetyltransferase, with affinities slightly lower than that of acetyl-CoA, indicating that these compounds are not good mimics of the enzyme-bound tetrahedral intermediate or transition state.

  DOI：

  10.1021/ja00090a014
• 作为产物：
  描述：

  sodium pantothenate 以 甲醇 、 二氯甲烷 为溶剂， 生成 pantothenic acid propyl thioester
  参考文献：
  名称：

  Synthesis of Novel Analogs of Acetyl Coenzyme A: Mimics of Enzyme Reaction Intermediates

  摘要：

  An improved method for the synthesis of analogs of coenzyme A (CoA) and its thioesters, which are modified in the thiol or thioester moiety, has been developed using a combination of chemical and enzymatic reactions, The enzymes catalyzing the last two steps of CoA biosynthesis were used to prepare a CoA analog (1c) in which an amide bond is replaced by a thioester bond and the thiol group is replaced by a methyl group. Reaction of 1c with a primary amine in aqueous solution results in aminolysis of the thioester linkage to form the desired CoA analog. Reaction with different amines permits the introduction of a variety of functional groups in place of the nor mal thiol or thioester group. This methodology has been used in the synthesis of five new analogs of acetyl-CoA in which the thioester sulfur is replaced by a methylene group and the acetyl group is replaced by carboxylate (14a), nitro (14b), carboxamide (14c), methyl sulfoxide (14d), and methyl sulfone (14e) groups. 14a-c were designed to mimic the possible enolate or enol intermediate in the reaction of citrate synthase and related enzymes. 14a and 14c are potent inhibitors of citrate synthase, with K-i values 1000- and 570-fold lower than the K-m for acetyl-CoA, respectively. CD titrations indicate that 14a and 14c have low affinity for citrate synthase in the absence of oxaloacetate, consistent with their recognition as enol or enolate analogs. 14b is a poor inhibitor of citrate synthase, with affinity slightly lower than that for acetyl-CoA. These results are consistent with generation of the enol form of acetyl-CoA as the nucleophilic intermediate in the reaction of citrate synthase. 14d and 14e were designed to mimic the tetrahedral intermediate or transition state in the reaction of chloramphenicol acetyltransferase and related acetyl-CoA-dependent acetyltransferases. Both compounds are poor inhibitors of chloramphenicol acetyltransferase, with affinities slightly lower than that of acetyl-CoA, indicating that these compounds are not good mimics of the enzyme-bound tetrahedral intermediate or transition state.

  DOI：

  10.1021/ja00090a014

文献信息

• A Highly Convergent Synthesis of Myristoyl-carba(dethia)-coenzyme A
  作者：Lutz Tautz、Janos Rétey

  DOI：10.1002/ejoc.200901410

  日期：2010.3

  following the route of the original CoA synthesis, generate such analogues in very low over all yields that typically are not sufficient for in vivo studies. Here, we present a new, highly convergent synthesis of myristoyl-carba(dethia)-coenzyme A 1 that allows to obtain this substrate analogue in 11-fold increased yield compared to the reported linear synthesis. In addition, enzymatic cleavage of the

  各种信号蛋白的N端甘氨酸残基的共翻译肉豆蔻酰基化是膜附着和这些分子正常功能所必需的。N-肉豆蔻酰基转移酶（Nmt）催化肉豆蔻酸从肉豆蔻酰基辅酶A（myr-CoA）的转移。Nmt与多种人类疾病有关，包括癌症和癫痫病以及诸如真菌和病毒感染（包括HIV和B型肝炎）的致病机制。合理的设计已导致开发了有效的竞争性抑制剂，包括几种非甾体抗炎药。可水解的酰基辅酶A底物类似物。然而，遵循原始CoA合成路线的线性合成策略，在通常不适合于体内研究的所有产量上，以非常低的产率生成此类类似物。在这里，我们提出一个新的，肉豆蔻酰基-氨基甲酸酯（dethia）-辅酶A 1的高度收敛合成，与报道的线性合成相比，该合成物可以以11倍增加的收率获得这种底物类似物。另外，在合成的最后一步中，对2'，3'-环磷酸腺苷的酶切被证明是获得异构纯3'-磷酸1的有效方法。