(R,S)-allyloxy(N,N-diisopropylamino)(2',3'-O-isopropylideneadenosin-5'-yloxy)phosphine | 237768-96-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: (R,S)-allyloxy(N,N-diisopropylamino)(2',3'-O-isopropylideneadenosin-5'-yloxy)phosphine
• CAS: 237768-96-6
• 化学式: C₂₂H₃₅N₆O₅P
• 分子量: 494.531
• InChiKey: IBAZHYOOBXHOIM-LGXGWTMCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.39
• 重原子数：
  34.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  119.01
• 氢给体数：
  1.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  (R,S)-allyloxy(N,N-diisopropylamino)(2',3'-O-isopropylideneadenosin-5'-yloxy)phosphine 在 四氮唑 、 四(三苯基膦)钯 、 间氯过氧苯甲酸 、 N-甲基苯胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 20.0h， 生成 Fmoc-Thr{PO[OH][OAMP(acetonide)]}-OH
  参考文献：
  名称：

  Fmoc-based solid-phase synthesis of adenylylated peptides using diester-type adenylylated amino acid derivatives

  摘要：

  Phosphodiester-type adenylylated (AMPylated) Ser, Thr, and Tyr derivatives were developed for Fmoc solid phase peptide synthesis of AMPylated peptides. One-pot/sequential reaction consisting of condensation of an N-nonprotected adenosine derivative and Fmoc-Ser/Thr/Tyr-OAllyl using allyl-N,N-diisopropylchlorophosphoramidite and subsequent oxidation with m-chloroperbenzoic acid gave phosphotriester-type AMPylated Ser/Thr/Tyr derivatives. After Pd(0)-mediated deprotection of allyl groups, the resulting phosphodiester-type AMPylated Ser/Thr/Tyr derivatives were successfully incorporated into peptides by standard Fmoc solid phase peptide synthesis without significant side reactions including dehydroalanine formation. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2012.04.063
• 作为产物：
  描述：

  N,N,N',N'-四(1-甲基乙基)-二氨基亚磷酸 2-丙烯-1-基酯 、 2',3'-异丙叉腺苷 在 四氮唑 作用下， 以 二氯甲烷 为溶剂， 以63%的产率得到(R,S)-allyloxy(N,N-diisopropylamino)(2',3'-O-isopropylideneadenosin-5'-yloxy)phosphine
  参考文献：
  名称：

  A sulfoximine-based inhibitor of human asparagine synthetase kills l-asparaginase-resistant leukemia cells

  摘要：

  An adenylated sulfoximine transition-state analogue 1, which inhibits human asparagine synthetase (hASNS) with nanomolar potency, has been reported to suppress the proliferation of an L-asparagine amidohydrolase (ASNase)-resistant MOLT-4 leukemia cell line (MOLT-4R) when L-asparagine is depleted in the medium. We now report the synthesis and biological activity of two new sulfoximine analogues of 1 that have been studied as part of systematic efforts to identify compounds with improved cell permeability and/or metabolic stability. One of these new analogues, an amino sulfoximine 5 having no net charge at cellular pH, is a better hASNS inhibitor (K*(I) = 8 nM) than 1 and suppresses proliferation of MOLT-4R cells at 10-fold lower concentration (IC50 = 0.1 mM). More importantly, and in contrast to the lead compound 1, the presence of sulfoximine 5 at concentrations above 0.25 mM causes the death of MOLT-4R cells even when ASNase is absent in the culture medium. The amino sulfoximine 5 exhibits different dose-response behavior when incubated with an ASNase-sensitive MOLT-4 cell line (MOLT-4S), supporting the hypothesis that sulfoximine 5 exerts its effect by inhibiting hASNS in the cell. Our work provides further evidence for the idea that hASNS represents a chemotherapeutic target for the treatment of leukemia, and perhaps other cancers, including those of the prostate. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.07.047

文献信息

• A Potent Transition-State Analogue Inhibitor of <i>Escherichia c</i><i>oli</i> Asparagine Synthetase A
  作者：Mitsuteru Koizumi、Jun Hiratake、Toru Nakatsu、Hiroaki Kato、Jun'ichi Oda

  DOI：10.1021/ja990851a

  日期：1999.6.1