Synthesis and hydrolysis of a phenylalanyl adenylate pentacoordinated phosphorane.
Amino acid-nucleotide conjugates have important biological functions and therapeutic applications. For example, aminoacyl adenylates are key intermediates in aminoacyl tRNA synthetase reactions. They may also be involved in the prebiotic synthesis of polypeptides. Finally, various amino acid carbomethoxy aryl phosphoramidates of nucleotide prodrugs may be activated through a mechanism involving a pentacoordinated phosphorane intermediates. In order to understand better the chemistry of these compounds, a phenylalanyl adenylate pentacoodinated phosphorane has been synthesized in 72% yield and its decomposition in aqueous solution studied. Hydrolysis gave 2('),3(')-O-isopropylidene adenosine 5(')-monophosphate, 2('),3(')-O-isopropylidene adenosine, and phenylalanine. The results provide model chemistry for the enzymatic degradation mechanism of antiviral aryl amino acid phosphodiester amidates in cells, which leads to their activation.
Fu
Hua
H
Department of Chemistry, School of Life Sciences and Engineering, Tsinghua University, Beijing 100084, People's Republic of China. fuhua@mail.tsinghua.edu.cn
Han
Bo
B
Zhao
Yu-Fen
YF
Tu
Guang-Zhong
GZ
Xu
Li
L
Lu
Qiang
Q
Wang
Jing-Zun
JZ
Xiao
Hong-Zhan
HZ
D000249:Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D006868:Hydrolysis; D009711:Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry
D009711:Nucleotides; D011355:Prodrugs; D000249:Adenosine Monophosphate