Efficient synthesis of an adenosine A2a agonist: glycosylation of 2-haloadenines and an N2-alkyl-6-chloroguanine.
A convergent synthesis of adenosine A2a agonist 1 in the form of its maleate salt 2 was achieved. The key step in this approach was the highly selective 9beta-glycosylation reaction between 2-haloadenines or an N(2)-alkyl-6-chloroguanine and a D-ribose derivative containing a 2-ethyltetrazolyl moiety. Glycosylations of other purine derivatives were also examined, and the methods developed provide efficient access to a variety of adenosine analogues such as 2-alkylaminoadenosines, an attractive class of compounds with antiinflammatory activity.
Caddell
John M
JM
Chemical Development, GlaxoSmithKline, Research Triangle Park, North Carolina 27709, USA.
Chapman
Alan M
AM
Cooley
Bob E
BE
Downey
Brian P
BP
LeBlanc
Michael P
MP
Jackson
Mary M
MM
O'Connell
Thomas M
TM
Phung
Hahn-My
HM
Roper
Thomas D
TD
Xie
Shiping
S
D000225:Adenine / Q000737:chemistry; D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D058908:Adenosine A2 Receptor Agonists; D000478:Alkylation; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis*; D006031:Glycosylation; D006147:Guanine / Q000031:analogs & derivatives; D006846:Hydrocarbons, Halogenated / Q000737:chemistry; D008298:Maleates / Q000737:chemistry; D015394:Molecular Structure; D011687:Purines / Q000737:chemistry; D012266:Ribose / Q000737:chemistry
D058908:Adenosine A2 Receptor Agonists; D000893:Anti-Inflammatory Agents; D006846:Hydrocarbons, Halogenated; D008298:Maleates; D011687:Purines; D006147:Guanine; D012266:Ribose; C030272:maleic acid; D000225:Adenine; D000241:Adenosine