55043-75-9Relevant academic research and scientific papers
Improved synthetic approaches toward 2'-O-methyl-adenosine and guanosine and their N-acyl derivatives
Beigelman, Leonid,Haeberli, Peter,Sweedler, David,Karpeisky, Alexander
, p. 1047 - 1056 (2007/10/03)
We developed several improved approaches toward 2'-O-methyl adenosine and guanosine and their N-acyl derivatives. (a) Transglycosylation of N4- acetyl-5', 3'-di-O-acetyl-2'-O-methyl cytidine with N6-Bz-adenine provided N6-benzoyl-5'3'-di-O-acetyl-2'-O-methyl adenosine in 50% yield. (b) Regioselective methylation of 2-amino-6-chloro purine riboside with MeI/NaH followed by hydrolysis provided 2'-O-Me-guanosine in high yield. The same 2'- O-Me-precursor was transformed into 2'-O-Me-adenosine in 58% yield. (c) Very efficient transformation of 2,6-diamino-purine riboside into N2-isobutyryl (isopropylphenoxyacetyl) 2'-O-Me-guanosine through methylation of 5',3'-O- TIPDSi derivative followed by selective N2-acylation, deamination and desylilation provided target compounds in 70% combined yield. (d) Mg2+ and Ag+ directed methylation of N1-Bzl-guanosine proceeded in >80% yield with ratio of 2'-O-Me-3'-O-Me=9:1. The same methylation of adenosine with Ag+ and Sr2+ acetylacetonates provided 2'-O-Me-adenosine in 75-80% yield. (C) 2000 Elsevier Science Ltd.
Synthesis and Properties of N2,3-Ethenoguanosine and N2,3-Ethenoguanosine 5'-Diphosphate
Kusmierek, Jaroslaw T.,Jensen, David E.,Spengler, Sylvia J.,Stolarski, Ryszard,Singer, B.
, p. 2374 - 2378 (2007/10/02)
N2,3-Ethenoguanosine has not been reported as a product of guanosine reaction with haloacetaldehydes.This is in contrast to the reaction of the ribosides yielding the well-known etheno compounds 1,N6-εAdo, 3,N4-εCyd, and 1,N2-εGuo.The base, N2,3-ethenoguanine was, however, synthesized, but not by direct reaction.We now report the synthesis of the nucleoside via reaction of O6-benzylguanosine with bromoacetaldehyde followed by hydrogenolytic debenzylation in the presence of palladium on charcoal.The structure of N2,3-ethenoguanosine was confirmed by NMR, UV, and FAB-MS data.The conformation of this nucleoside resembles that of guanosine, being predominantly in the anti form.The nucleoside was stable at neutrality, 37 deg C, but depurination was rapid at pH 1,24 deg C, with a t1/2 = 16 min.In contrast to 1,N2-εGuo, the angular N2,3-etheno derivatives are fluorescent, with the base having considerably higher fluorescence than the nucleoside.N2,3-Ethenoguanosine was converted to the 5'-diphosphate by conventional methods.This compound was a substrate for polynucleotide phosphorylase and could be copolymerized with CDP or ADP.There is little quench of the nucleotide fluorescence in copolymers.The recent report that N2,3-ethenoguanine is detected in chloroacetaldehyde-treated DNA after depurination makes N2,3-etheno modification of the guanine moiety of potential importance in understanding vinyl chloride induced carcinogenesis.
