(S)-methyl 2-((tert-butoxycarbonyl)amino)-3-((((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)thio)-3-methylbutanoate | 1346422-59-0

• 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)-methyl 2-((tert-butoxycarbonyl)amino)-3-((((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)thio)-3-methylbutanoate
• 英文别名: methyl (2S)-3-[[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methylsulfanyl]-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate
• CAS: 1346422-59-0
• 化学式: C₁₇H₃₁NO₆S
• 分子量: 377.502
• InChiKey: HGVPZJHUONIOGW-NEPJUHHUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-methyl 2-((tert-butoxycarbonyl)amino)-3-((((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)thio)-3-methylbutanoate 在 4-二甲氨基吡啶 、 水 、 1-羟基苯并三唑 、 溶剂黄146 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 53.0h， 生成 (R)-3-(((S)-4-(((S)-3-(tert-butoxy)-1-methoxy-1-oxopropan-2-yl)amino)-3-((tert-butoxycarbonyl)amino)-2-methyl-4-oxobutan-2-yl)thio)propane-1,2-diyl dipalmitate
  参考文献：
  名称：

  Structure–Activity Relationships in Toll-Like Receptor 2-Agonists Leading to Simplified Monoacyl Lipopeptides

  摘要：

  Toll-like receptor 2-agonistic lipopeptides typified by S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-R-cystein-yl-S-serine (PAM(2)CS) compounds are potential vaccine adjuvants. In continuation of previously reported structure activity relationships on this chemotype, we have determined that at least one acyl group of optimal length (C-16) and an appropriately oriented ester carbonyl group is essential for TLR2-agonistic activity. The spacing between one of the palmitoyl ester carbonyl and the thioether is crucial to allow for an important H-bond, which observed in the crystal structure of the lipopeptide:TLR2 complex; consequently, activity is lost in homologated compounds. Penicillamine-derived analogues are also inactive, likely due to unfavorable steric interactions with the carbonyl of Ser 12 in TLR2. The thioether in this chemotype can be replaced with a selenoether. Importantly, the thioglycerol motif can be dispensed with altogether and can be replaced with a thioethanol bridge. These results have led to a structurally simpler, synthetically more accessible, and water-soluble analogue possessing strong TLR2-agonistic activities in human blood,

  DOI：

  10.1021/jm201071e
• 作为产物：
  描述：

  N-Boc-(S)-Penicillaminmethylester 、 2,2-二甲基-4(r)-4-碘甲基-1,3-二氧杂烷 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 以65%的产率得到(S)-methyl 2-((tert-butoxycarbonyl)amino)-3-((((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)thio)-3-methylbutanoate
  参考文献：
  名称：

  Structure–Activity Relationships in Toll-Like Receptor 2-Agonists Leading to Simplified Monoacyl Lipopeptides

  摘要：

  Toll-like receptor 2-agonistic lipopeptides typified by S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-R-cystein-yl-S-serine (PAM(2)CS) compounds are potential vaccine adjuvants. In continuation of previously reported structure activity relationships on this chemotype, we have determined that at least one acyl group of optimal length (C-16) and an appropriately oriented ester carbonyl group is essential for TLR2-agonistic activity. The spacing between one of the palmitoyl ester carbonyl and the thioether is crucial to allow for an important H-bond, which observed in the crystal structure of the lipopeptide:TLR2 complex; consequently, activity is lost in homologated compounds. Penicillamine-derived analogues are also inactive, likely due to unfavorable steric interactions with the carbonyl of Ser 12 in TLR2. The thioether in this chemotype can be replaced with a selenoether. Importantly, the thioglycerol motif can be dispensed with altogether and can be replaced with a thioethanol bridge. These results have led to a structurally simpler, synthetically more accessible, and water-soluble analogue possessing strong TLR2-agonistic activities in human blood,

  DOI：

  10.1021/jm201071e

文献信息

• Structure–Activity Relationships in Toll-Like Receptor 2-Agonists Leading to Simplified Monoacyl Lipopeptides
  作者：Geetanjali Agnihotri、Breanna M. Crall、Tyler C. Lewis、Timothy P. Day、Rajalakshmi Balakrishna、Hemamali J. Warshakoon、Subbalakshmi S. Malladi、Sunil A. David

  DOI：10.1021/jm201071e

  日期：2011.12.8

  Toll-like receptor 2-agonistic lipopeptides typified by S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-R-cystein-yl-S-serine (PAM(2)CS) compounds are potential vaccine adjuvants. In continuation of previously reported structure activity relationships on this chemotype, we have determined that at least one acyl group of optimal length (C-16) and an appropriately oriented ester carbonyl group is essential for TLR2-agonistic activity. The spacing between one of the palmitoyl ester carbonyl and the thioether is crucial to allow for an important H-bond, which observed in the crystal structure of the lipopeptide:TLR2 complex; consequently, activity is lost in homologated compounds. Penicillamine-derived analogues are also inactive, likely due to unfavorable steric interactions with the carbonyl of Ser 12 in TLR2. The thioether in this chemotype can be replaced with a selenoether. Importantly, the thioglycerol motif can be dispensed with altogether and can be replaced with a thioethanol bridge. These results have led to a structurally simpler, synthetically more accessible, and water-soluble analogue possessing strong TLR2-agonistic activities in human blood,