501416-89-3Relevant academic research and scientific papers
Addition of ester enolates to N-alkyl-2-fluoropyridinium salts: Total synthesis of (±)-20-deoxycamptothecin and (+)-camptothecin
Bennasar, M.-Lluisa,Zulaica, Ester,Juan, Cecilia,Alonso, Yolanda,Bosch, Joan
, p. 7465 - 7474 (2007/10/03)
Several 4-substituted dihydropyridones or 2-pyridones have been prepared by nucleophilic addition of α-(methylsulfanyl)ester enolates to N-alkyl-2-fluoropyridinium salts, followed by acid hydrolysis or oxidation with concomitant hydrolysis, of the intermediate 2-fluoro-1,4-dihydropyridine adducts, respectively. Addition of the enolate derived from isopropyl α-(methylsulfanyl)butyrate to N-(quinolylmethyl)-2-fluoropyridinium triflate 21 followed by DDQ treatment gave pyridone 29, from which (±)-20-deoxycamptothecin (31), a known precursor of camptothecin, was synthesized by a radical cyclization-desulfurization, with subsequent elaboration of the lactone E ring by chemoselective reduction. A similar sequence starting from the enolate of a chiral 2-hydroxybutyric acid derivative (33) provides access to natural (+)-camptothecin (37).
