SYNTHESIS OF 2-FLUORO AND 6-FLUORO ANALOGS OF THREO-3-(3,4-DIHYDROXYPHENYL) SERINE (2-FLUORO-THREO-DOPS AND 6-FLUORO-THREO-DOPS)

2-Fluoro- and 6-fluoro-threo-dihydroxyphenylserine (2-F- and 6-F-threo-DOPS) have the potential, after crossing the blood-brain barrier, of functioning in the central nervous system as biological precursors of 2- and 6-fluoronorepinephrine (2- and 6-F-NE). Since 2-F-NE is a selective beta-adrenergic agonist and 6-F-NE is a selective alpha-adrenergic agonist, subsequent selective actions at beta- and alpha-adrenergic receptors could be beneficial for both clinical and pharmacological studies. We have prepared 2- and 6-F-threo-DOPS by the ZnCl2-catalyzed reaction of a protected glycine trimethylsilylketene acetal with benzyl-protected 2- and 6-fluoroprocatechuealdehyde. Other enantio- and diastereoselective approaches to these analogues either gave no product or produced predominantly the erythro diastereomer, apparently formed during work-up by acid-promoted racemization of the benzylic OH group in compounds possessing an unprotected catechol.