Improved Synthetic Approaches Toward 2′-O-Methyl-Adenosine and Guanosine and Their N-Acyl Derivatives

Autor:	Peter Haeberli, Leonid Beigelman, Alexander Karpeisky, David Sweedler
Rok vydání:	2000
Předmět:	Chemistry Stereochemistry Organic Chemistry Deamination Guanosine Methylation Riboside Biochemistry Adenosine Acylation Hydrolysis chemistry.chemical_compound Yield (chemistry) Drug Discovery medicine medicine.drug
Zdroj:	Tetrahedron. 56:1047-1056
ISSN:	0040-4020
Popis:	We developed several improved approaches toward 2′- O -methyl adenosine and guanosine and their N -acyl derivatives. (a) Transglycosylation of N 4 -acetyl-5′, 3′-di- O -acetyl-2′- O -methyl cytidine with N 6 -Bz-adenine provided N 6 -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 N 2 -isobutyryl (isopropylphenoxyacetyl) 2′- O -Me-guanosine through methylation of 5′,3′- O -TIPDSi derivative followed by selective N 2 -acylation, deamination and desylilation provided target compounds in 70% combined yield. (d) Mg 2+ and Ag + directed methylation of N 1 -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 Sr 2+ acetylacetonates provided 2′- O -Me-adenosine in 75–80% yield.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::326ec0c6e4a13b8231ffda7a21e06954 https://doi.org/10.1016/s0040-4020(00)00002-8 Zobrazit plný text záznamu Full Text from ScienceDirect