The synthesis of the first of these starts with the formation of the enamide
( 18 ) from tyrosine ( 16 ) and 2-benzoylcyclohexanone ( 17 ). Treatment of that
product with palladium on charcoal leads to dehydrogenation of the ene-
amide ring with consequent aromatization. Condensation of the terminal
hydroxyl group on the side chain in the substituted oxazole ( 21 ) with the
phenolfunction on 20 in the presence of triphenylphosphine and diethyl azo-
dicorboxylate (DEAD) leads to formation of an ether bond. This reaction
affords the hypoglycemic agentfarglitazar( 22 ).^4
HOCO 2 CH 3
NH 2
16+OHO17HOCO 2 CH 3HON18HOCO 2 CH 3OHN19HOCO 2 CH 3OHN20N
O
CH 3
(C 6 H 5 ) 3 P, DEADOCO 2 CH 3OHNN
O
CH 3OH2122An aryl carbamate replaces the tyrosine moiety in a related analogue.
The preparation of this compound first involves activation of the side-
chain oxygen in the same oxazole used above ( 21 ) by conversion to its
mesylate (21a) by means of methanesulfonyl chloride. This intermediate
N
O
CH 3R(^21) 21a; R = H; R = OSO
2 CH 3
- CH=O
23
K 2 CO 3
N
O
CH 3
O
CH=O
HO
- H 2 NCH 2 CO 2 CH 3
- NaBH 4
N
O
CH 3ONH CO 2 CH 3OCl
OOCH 3242526N
O
CH 3ON CO 2 CH 3
O O(^27) OCH 3
46 MONOCYCLIC AROMATIC COMPOUNDS