An elegant synthesis of (+)-exo-brevicomin, the sex pheromone of bark beetles
made use of FDP-aldolase (Scheme 2.184) [1547]. RAMA-catalyzed addition of
DHAP to a δ-keto-aldehyde gave, after enzymatic dephosphorylation, a threo-ketodiol, which was cyclized to form a precursor of the pheromone. Finally, the side
chain was de-functionalized in four subsequent steps to give (+)-exo-brevicomin.
Despite the fact that enzymatic aldol reactions are becoming useful in synthetic
carbohydrate chemistry, the preparation of aldehyde substrates containing chiral
centers remains a problem. Many α-substituted aldehydes racemize in aqueous
solution, which would result in the production of a diastereomeric mixture, which
is not always readily separable.
O
OH +
O
OH
OH
OH
O
N 3
O
OH
OH
OH
O
N 3
O
OH
O
N 3
H
OH
OH
HO
HO
NH
HO
OH
HO
HO
NH
* newly formed
stereocenters
* *
= phosphate
DHAP
FDP aldolase
+
deoxynojirimycin
deoxymannojirimycin
* *
phosphatase
then H 2 /Pd
phosphatase
then H 2 /Pd
P
P
P
P
5
5
Scheme 2.183 Synthesis of aza-sugar analogs
O
O
O
OH
O
O
O
OH
OH
O
OH
O
O
H
(+)-exo-brevicomin
four steps
phosphatase
FDP aldolase
+ DHAP
* newly formed stereocenters
*
*
H
+
Scheme 2.184 Synthesis of (+)-exo-brevicomin
210
2 Biocatalytic Applications