Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan.
Chem Rec. 2009;9(6):305-20. doi: 10.1002/tcr.200900017.
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).
各种用于合成红霉素 A 的 aglycon 赤藓糖内酯 A 的中间体可通过使用 2-甲基-6-硝基苯甲酸酐 (MNBA) 在 4-(二甲氨基)吡啶 (DMAP) 的存在下从相应的 sec 酸来制备，而无需添加三乙胺。通过研究该方法并将结果与其他已建立的大环化方案进行比较，评估了 MNBA 内酯化的效率。最终得出结论：(i) 对于单体环化，构象合适的底物在 MNBA 和 DMAP 的存在下在温和的反应条件下以优异的收率得到所需的内酯；(ii) 对于环化的高度应变底物也在 100°C 的甲苯中以相对较好的收率得到单体内酯；以及 (iii) 具有稳定线性构象的 sec 酸更喜欢二聚而不是形成单体内酯，以高收率提供相应的二醇内酯，单体与二聚体内酯的比例保持不变（约 1/5）。
