The synthesis of all the possible isomers of the eburnameninevincamine type alkaloids l b , 2a*, 3a and derivatives 4, 8, 9, 10 is described. Structures were determined by 'H-and 13C-NMR spectroscopy including special techniques such as DR, DEPT, DNOE, and 2D-HSC. In contrast to the known cerebrovascular effects of cis-(3S,lGS) compounds, trans-(3S,lGR) derivatives show a significant peripheral vasodilator effect.

A series of trans-2'-hydroxyethyl and 2'-acyloxyethyl apovincaminates 4b- f and 7b- f has been synthesized and evaluated for their antioxidant and antiamnesic effects. The new esters were prepared from 4a and 7a ethyl esters or from the corresponding carboxylic acid sodium salt. For starting materials 11a, b, a new stereoselective trans-reduction was elaborated. From the combined results of the data obtained from in vitro and in vivo tests and examination of the metabolism, (3 R,16 S)-2'-hydroxyethyl apovincaminate ( 7b, RGH-10885) was identified as the most promising compound, owing to its potent neuroprotective and antiamnesic activities. The in vivo effectiveness of selected compounds on the cognitive functions was studied in a one-trial passive avoidance task and a water-labyrinth test.

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