The beta-lactone route to a totally stereoselective synthesis of carnitine derivatives

The syntheses of the enantiomerically pure, carnitine-related beta-lactones 10 and 12 starling ii-om various carnitine precursors of opposite configuration (or carnitine itself) are described. (R)-3-Chlorocarnitine (20) has also been directly prepared from (S)-carnitine (14) and has been cyclized to 12 by a second inversion of configuration of thr stereogenic centre. By nucleophilic attack at the carbonyl carbon, the beta-lactone carnitine derivatives have been converted into esters, amides and guanidino congeners. Following this route, it is possible to obtain the biologically active isomer (R)-carnitine (1) starting from the otherwise useless industrial by-product (S)carnitine (14). Nucleophilic attack by selected am bident nucleophiles at the beta-carbon of the same beta-lactone derivatives results in a second inversion of configuration of the stereogenic centre. Besides aminocarnitine (3). chiral acetylcarnitine (2) and acetylthiocarnitine (S) have been synthesized in homochiral forms following this latter procedure.