Nouvelle methode de synthese des principaux metabolites des catecholamines marques au carbone 14

Abstract

AbstractMethylsulfinylcarbanion used in large excess reacts with methyl (carboxyl 14C) vanillate 2 a, methyl (carboxyl 14C) isovanillate 2 b and methyl 3,4 dibenzyloxy (carboxyl 14C) benzoate 2 d to give 90 % yields of β‐ketosulfoxides 3 a, 3 b, 3 d. Submitted to the acid catalyzed Pummerer rearrangement these β‐ketosulfoxides lead to the formation of methyl hemimercaptals of phenylglyoxals 4 a, 4 b, 4 d in good yields. These β‐keto‐α‐hydroxy sulfides react with sodium hydroxide to give respectively : 2–(4–hydroxy‐3‐methoxyphenyl)‐2‐hydroxy (2–14C) acetic acid 5 a (V.M.A.); 2–(3‐hydroxy‐4‐methoxyphenyl)‐2‐hydroxy (2–14C) acetic acid 5 b (iso V.M.A.) in overall yields of 55 % based on vanillic and iso‐vanillic acids; and 2–(3,4 dibenzyloxyphényl)‐2 hydroxy (2–14C) acetic acid 5 d, hydrogenolysis of which gave 2–(3,4 dihydroxyphenyl)‐2‐hydroxy (2–14C) acetic acid (D.H.M.A.) in 61 % overall yield from 3,4 dihydroxy benzoic acid. The β‐keto‐α‐hydroxysulfides 4 a, 4 b, 4 d reduced with sodium borohydride give respectively 2‐(4‐hydroxy‐3‐methoxyphenyl) (2–14C) ethyleneglycol (H.M.P.G.) 6 a; 2–(3‐hydroxy‐4‐methoxyphenyl) (2–14C) ethyleneglycol 6 b (iso H.M.P.G.) in overall yields of 64 % and 60 % based on vanillic and isovanillic acids; and glycol 6 d the hydrogenolysis of which gave 2–(3,4‐dihydroxyphenyl) (2–14C) ethyleneglycol 6 c (D.H.P.G.) in yield of 64 % based on 3,4 dihydroxybenzoic acid.