Evaluation of the efficiency of the macrolactonization using MNBA in the synthesis of erythromycin A aglycon.
Various intermediates for the synthesis of erythronolide A, an aglycon of erythromycin A, are prepared from the corresponding seco-acids using 2-methyl-6-nitrobenzoic anhydride (MNBA) in the presence of 4-(dimethylamino)pyridine (DMAP) with or without triethylamine. The efficiency of the MNBA lactonization is assessed by studying this method and comparing the results with those of the other established macrocyclization protocols. It has been finally concluded that (i) the conformationally appropriate substrate for the monomeric cyclization gave the desired lactone in excellent yield under mild reaction conditions in the presence of MNBA and DMAP, (ii) the highly-strained substrate for the cyclization also afforded the monomeric lactone in relatively good yield at 100 degrees C in toluene, and (iii) the seco-acid having stable linear conformation, which preferred dimerizing more than forming the monomeric lactone, provided the corresponding diolide in high yield with the constant ratio of the monomer to dimeric lactone (approximately 1/5).
Shiina
Isamu
I
Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan. Shiina@kagu.tus.ac.jp
Katoh
Takashi
T
Nagai
Shunsuke
S
Hashizume
Minako
M
D000812:Anhydrides / Q000737:chemistry*; D003500:Cyclization; D004917:Erythromycin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry*; D018942:Macrolides / Q000138:chemical synthesis / Q000737:chemistry; D009579:Nitrobenzoates / Q000737:chemistry*
C526944:2-methyl-6-nitrobenzoic anhydride; D000812:Anhydrides; D007783:Lactones; D018942:Macrolides; D009579:Nitrobenzoates; C038316:erythronolide A; D004917:Erythromycin