Drug Metabolism in Drug Design and Development Basic Concepts and Practice

3. Aromatic

hydroxylation(Gerhard et al.,2003)

NNH

O

O

HN

F

NH

N

O

O

HN

F

OH

2 4

The hydroxylation position at

C2 or at C4 was not obviousfrom the 1D proton spectrumdue to the presence of theF



H couplings

No further experiment is

needed to confirm theregiochemistry

2D COSY spectrum indicated

the larger doublet at

d7.25

(8.1 Hz) was due to vicinalcoupling of F



H while the

smaller coupling (2.3 Hz) wasthe result of H2



H6 meta

coupling

Based on the coupling

constant, the hydroxylationoccurred at the C4 position

4. Epoxidation

(Garcia et al.,2004)

HN

O

NH

2

HN

O

NH

2

O

13,14-E

pox

y Hu

perzine A

Hu

perzine A

The olefinic protons shifted

from

d6.12 to

d2.79 ppm.

This observation ischaracteristic for epoxidein which the protonnormally appears atd2.2–2.9 ppm

The formation of epoxide

can be confirmed bydetermining the shifts ofC13 and C14 carbonsinvolved in epoxide formationeither by performing

1 H



13

C

HMQC or direct

13

C

1D

experiments. Both carbonsshould shift from



130 to



50 ppm.

(continued

)

399