Parallel synthesis of novel heteroaromatic acromelic acid analogues from kainic acid.
A range of new C-4 heteroaromatic acromelic acid analogues has been synthesized in a parallel fashion from (-)-alpha-kainic acid 1. Protection of the amine and carboxylate groups of 1 followed by ozonolysis gave methyl ketone 8. A silyl enol ether 9, generated regiospecifically from the methyl ketone 8 using "kinetic" conditions, was brominated in situ with phenyltrimethylammonium perbromide to give the key alpha-bromo ketone 10. Parallel cyclization reactions of bromo ketone 10 with thioamides and thioureas were then performed. The aromatic heterocyclic derivatives 11a-d and 19 produced were deprotected to give the new kainoid amino acids 6a-d and 25 in excellent yield. Compounds 6a and 6c show strong binding to the kainate receptor. Reaction of 10 with alternative condensing agents was also briefly investigated.
Baldwin
J E
JE
The Dyson Perrins Laboratory, South Parks Road, Oxford OX1 3QY, U.K. jack.baldwin@chem.ox.ac.uk
Fryer
A M
AM
Pritchard
G J
GJ
D000818:Animals; D000871:Anthelmintics / Q000138:chemical synthesis; D018690:Excitatory Amino Acid Agonists / Q000138:chemical synthesis; D018691:Excitatory Amino Acid Antagonists / Q000138:chemical synthesis; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D006801:Humans; D007306:Insecticides / Q000138:chemical synthesis; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis*
D000871:Anthelmintics; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D006571:Heterocyclic Compounds; D007306:Insecticides; C051743:acromelic acid A; D007608:Kainic Acid; C438458:acromelic acid B