L-serine N-acetylcysteamine thioester hydrochloride | 1001401-80-4

• 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: L-serine N-acetylcysteamine thioester hydrochloride
• CAS: 1001401-80-4
• 化学式: C₇H₁₄N₂O₃S*ClH
• 分子量: 242.727
• InChiKey: QYMCDFNULGLRBK-RGMNGODLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.88
• 重原子数：
  14.0
• 可旋转键数：
  5.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  92.42
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  L-serine N-acetylcysteamine thioester hydrochloride 、 己酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以78%的产率得到Nα-hexanoyl-L-serine N-acetylcysteamine thioester
  参考文献：
  名称：

  Engineered Biosynthesis of Nonribosomal Lipopeptides with Modified Fatty Acid Side Chains

  摘要：

  The biological properties of the calcium-dependent antibiotics (CDAs), daptomycin and related nonribosomal lipopeptides, depend to a large extent on the nature of the N-terminal fatty acid moiety. It is suggested that the chain length of the unusually short (C6) 2,3-epoxyhexanoyl fatty acid moiety of CDA is determined by the specificity of the KAS-II enzyme encoded by fabF3 in the CDA biosynthetic gene cluster. Indeed, deletion of the downstream gene hxcO results in three new lipopeptides, all of which possess hexanoyl side chains (hCDAs). This confirms that HxcO functions as a hexanoyl-CoA or -ACP oxidase. The absence of additional CDA products with longer fatty acid groups further suggests that the CDA lipid chain is biosynthesized on a single ACIP and is then transferred directly from this ACID to the first CDA peptide synthetase (CdaPS1). Interestingly, the hexanoyl-containing CDAs retain antibiotic activity. To further modulate the biological properties of CDA by introducing alternative fatty acid groups, a mutasynthesis approach was developed. This involved mutating the key active site Set residue of the CdaPS1, module 1 PCP domain to Ala, which prevents subsequent phosphopantetheinylation. In the absence of the natural module 1 PCP tethered intermediate, it is possible to effect incorporation of different N-acyl-L-serinyl N-acetylcysteamine (NAC) thioester analogues, leading to CDA products with pentanoyl as well as hexanoyl side chains.

  DOI：

  10.1021/ja074331o
• 作为产物：
  描述：

  Nα-tert-butoxycarbonyl-O-tert-butyl-L-serine N-acetylcysteamine thioester 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.17h， 以79%的产率得到L-serine N-acetylcysteamine thioester hydrochloride
  参考文献：
  名称：

  Engineered Biosynthesis of Nonribosomal Lipopeptides with Modified Fatty Acid Side Chains

  摘要：

  The biological properties of the calcium-dependent antibiotics (CDAs), daptomycin and related nonribosomal lipopeptides, depend to a large extent on the nature of the N-terminal fatty acid moiety. It is suggested that the chain length of the unusually short (C6) 2,3-epoxyhexanoyl fatty acid moiety of CDA is determined by the specificity of the KAS-II enzyme encoded by fabF3 in the CDA biosynthetic gene cluster. Indeed, deletion of the downstream gene hxcO results in three new lipopeptides, all of which possess hexanoyl side chains (hCDAs). This confirms that HxcO functions as a hexanoyl-CoA or -ACP oxidase. The absence of additional CDA products with longer fatty acid groups further suggests that the CDA lipid chain is biosynthesized on a single ACIP and is then transferred directly from this ACID to the first CDA peptide synthetase (CdaPS1). Interestingly, the hexanoyl-containing CDAs retain antibiotic activity. To further modulate the biological properties of CDA by introducing alternative fatty acid groups, a mutasynthesis approach was developed. This involved mutating the key active site Set residue of the CdaPS1, module 1 PCP domain to Ala, which prevents subsequent phosphopantetheinylation. In the absence of the natural module 1 PCP tethered intermediate, it is possible to effect incorporation of different N-acyl-L-serinyl N-acetylcysteamine (NAC) thioester analogues, leading to CDA products with pentanoyl as well as hexanoyl side chains.

  DOI：

  10.1021/ja074331o