Chemistry Reference
In-Depth Information
(c) The
trans
elimination of water from (
S
)-malic acid must remove the groups shown in bold. We then substitute
one of the hydrogens at position 3 with
2
H (deuterium; D) to get the 3
S
configuration by the trial-and-error
procedure in (b). (2
S
,3
S
)-[3-
2
H]malic acid is thus labelled as shown, and
trans
elimination of water must
result in the deuterium label ending up as shown in fumaric acid.
trans
elimination
H
H
H
CO
2
H
CO
2
H
HO
2
C
- H
2
O
HO
2
C
H
HO
H
priority 4
priority 3
trans
elimination
H
D
D
CO
2
H
S
S
CO
2
H
HO
2
C
- H
2
O
HO
2
C
H
priority 1
HO
H
priority 2
(2
S
,3
S
)-[3-
2
H]malic acid
(d) As soon as you have written down the reagents, you will find the reaction follows quite readily. We have
simple nucleophilic addition to an aldehyde.
nucleophilic atack of hydroxide
onto thioester carbonyl
O
acetyl-CoA
HOH
H
2
C
SCoA
OH
OH
O
OH
OH
H
O
H
SCoA
H
SCoA
H
SCoA
CO
2
H
CO
2
H
O
CO
2
H
O
CO
2
H
O
glyoxylic acid
protonation
from solvent
loss of leaving
group
intermediate thioester
nucleophilic attack of
acetyl-Co-derived anion
onto aldehyde
OH
H
OH
SCoA
CO
2
H
O
malic acid
(e) The intermediate thioester is then hydrolysed by base as included above.
(f) Now for the stereochemistry. Draw the malic acid product with the 2
S
configuration. It is also possible to
turn around the structure obtained in part (b). You can only get this configuration if the planar aldehyde is
attacked from the face shown. This is the
Si
face, using the priority rules for enantiotopic faces, which are
an extension of the Cahn - Ingold - Prelog
R
and
S
system.
turn structure round, or redraw
it with S stereochemistry
priority 1
O
OH
O
Si
CO
2
H
HO
Nu
H
OH
≡
HO
2
C
Nu
H
HO
H
HO
2
C
H
CO
2
H
H
CO
2
H
CO
2
H
O
priority 2
priority 3
(
S
)-malic acid
(
S
)-malic acid
to get this stereochemistry,
must attack from face shown
from (b)
from (d)
front (Si) face
is attacked
