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Cl

Cl N

OH N N N NH

N

Cl

N

O N N N NH

N alcohol oxidation

losartan (Cozaar) antihypertensive

N

OH

N

O

alcohol oxidation

aldehyde metabolite

N N N NH

acid metabolite

sp2 hybridized carbon oxidations Oxidations of sp2 hybridized carbons normally involve aromatic rings. The aromatic ring is initially epoxized, and the epoxide rearranges to restore aromaticity and form a phenol. The rearrangement is frequently not regioselective, and isomeric metabolites may be observed. Me

Me

H N O Me

H

HO

N oxidation

3

O Me

ropivacaine (Naropin) local anesthetic

Me

H N

N

H

HO

3-hydroxy metabolite

H N O Me

4

H

N

4-hydroxy metabolite

heteroatom oxidations Heteroatom oxidations occur on sulfur atoms and nitrogens, especially sp 2 hybridized nitrogens. Me N

Me N

N

O N

N Cl

Cl N H clozapine (Clozaril) antipsychotic

Me HN

N

S

H N

NHMe N

N cimetidine (Tagamet) acid reflux

N H clozapine N-oxide

Me HN

CN

N

S O

H N

NHMe N

cimetidine sulfoxide

CN

MOOC Medicinal Chemistry