Progess towards the total synthesis of the antifungal natural product (-)-pramanicin

Unrestricted Progress towards the total synthesis of the antifungal natural product (-)-pramanicin and efficient synthesis of its side chain, (E)-4,5-epoxy-2-tetradecenoic acid, are reported. (-)-Pramanicin consists of a functionalized lipophilic side chain bound to a chiral gamma-lactam head group. The key synthetic steps include: (i) oxygen-promoted palladium-catalyzed cross-coupling of an aliphatic alkenyl-boron compound with methyl acrylate, (ii) stereo- and regioselective monoepoxidation of the resultant diene, (iii) rhodium(II)-catalyzed intramolecular C-H insertion of an alpha-diazoacetamide to afford a bicyclic gamma-lactam, and (iv) lithium diisopropylamide promoted condensation of an alpha,beta-unsaturated, gamma,delta-epoxy aldehyde with the bicyclic gamma-lactam.本研究报道了抗真菌天然产物(-)-普拉米星（(-)-pramanicin）的全合成及其侧链(E)-4,5-环氧-2-十四碳烯酸的高效合成的全面研究进展。(-)-普拉米星由连接于手性γ-内酰胺（gamma-lactam）头部基团的功能化亲脂性侧链组成。核心合成步骤包括：(i) 氧气促进的钯催化脂肪族烯基硼化合物与丙烯酸甲酯的交叉偶联反应；(ii) 对所得二烯烃进行立体选择性与区域选择性的单环氧化反应；(iii) 铑(II)催化α-重氮乙酰胺（alpha-diazoacetamide）的分子内C-H插入反应，以构建双环γ-内酰胺骨架；(iv) 二异丙基氨基锂（lithium diisopropylamide）促进的α,β-不饱和γ,δ-环氧醛与双环γ-内酰胺的缩合反应。