Position of coordination of the lithium ion determines the regioselectivity of demethylations of 3,4-dimethoxymorphinans with L-selectride.
[reaction: see text] L-Selectride is an efficient agent for the 3-O-demethylation of opioids and is known to cleave the least hindered methoxyl group in a molecule. The treatment of a 3,4-dimethoxymorphinan containing a 6-ketal with L-Selectride gave selective 4-O-demethylation, rather than cleavage of the less hindered 3-methoxyl. In contrast, a 3,4-dimethoxymorphinan lacking a 6-ketal gave selective 3-O-demethylation, suggesting that the regiochemistry of L-Selectride-mediated O-demethylation can be manipulated through altering the position of coordination of the lithium ion.
Wu
Huifang
H
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 Penn Street, Baltimore, Maryland 21201, USA.
Thatcher
Linn N
LN
Bernard
Denzil
D
Parrish
Damon A
DA
Deschamps
Jeffrey R
JR
Rice
Kenner C
KC
MacKerell
Alexander D
AD
Coop
Andrew
A
D002384:Catalysis; D007202:Indicators and Reagents; D008094:Lithium / Q000737:chemistry*; D015394:Molecular Structure; D009019:Morphinans / Q000737:chemistry*; D009294:Narcotics / Q000737:chemistry*; D013237:Stereoisomerism
D007202:Indicators and Reagents; D009019:Morphinans; D009294:Narcotics; D008094:Lithium