A chiral synthesis of (-)-spiro[1-azabicyclo[2.2.2]octane-3,5'- oxazolidin-2'-one]: a conformationally restricted analogue of acetylcholine that is a potent and selective alpha7 nicotinic receptor agonist.
A direct, short chiral synthesis of the selective alpha7 nicotinic receptor agonist (-)-spiro[1-azabicyclo[2.2.2]octane-3,5'-oxazolidin-2'-one] (AR-R17779) is presented. The key step utilized attack of the dianion of the (R)-HYTRA ester [(R)-(+)-2-hydroxy-1,2,2-triphenylethyl acetate] on quinuclidin-3-one, followed by a selective precipitation of the diasteriomeric tertiary alcohol that led to (S)-(-)-AR-R17779 in two additional steps.
Macor
John E
JE
CNS Discovery, AstraZeneca, 1800 Concord Pike, Wilmington, Delaware 19850-5437, USA. john.macor@bms.com
Mullen
George
G
Verhoest
Patrick
P
Sampognaro
Anthony
A
Shepardson
Bruce
B
Mack
Robert A
RA
D001952:Bridged-Ring Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D018722:Nicotinic Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
C408128:AR-R 17779; D001952:Bridged-Ring Compounds; D018722:Nicotinic Agonists; D013141:Spiro Compounds