State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China.
Chem Asian J. 2011 Feb 1;6(2):573-9. doi: 10.1002/asia.201000556. Epub 2010 Dec 14.
Condensation of (S)-3-aminobutan-1-ol with 1,3-cyclohexane-dione followed by an intramolecular alkylation afforded bicyclic enamine 32, which was converted into enone 35 through a diastereoselective hydrogenation. Mukaiyama-Michael addition of a bicyclic silyl enol ether to 35 and subsequent stereochemistry inversion by means of an oxidation/reduction strategy provided lactone 41. After reduction of lactone 41 with LAH, Swern oxidation was carried out to give enone 46 upon a spontaneous intramolecular aldol reaction and cleavage of the ketal protecting group. SmI(2) -mediated carbonyl-alkene reductive coupling of 46 proceeded smoothly in refluxing tetrahydrofuran to deliver pentacyclic intermediate 49, which was oxidized with 2-iodoxybenzoic acid and then treated with trifluoroacetic acid to furnish (-)-GB 13. The overall yield was 6.1% over 19 linear steps. By following the known procedure, our synthetic (-)-GB 13 was converted into himgaline. In addition, by starting from lactone 41, the first total synthesis of (+)-GB 16, a newly isolated member of the gabulimima alkaloid family, was achieved. This synthesis features an intramolecular condensation between an amine and a 1,3-diketone moiety.
（S）-3-氨基-1-丁醇与 1,3-环己二酮缩合，然后进行分子内烷基化，得到双环烯胺 32，通过立体选择性氢化将其转化为烯酮 35。双环硅基烯醇醚与 35 的 Mukaiyama-Michael 加成，通过氧化/还原策略进行立体化学反转，得到内酯 41。内酯 41 用 LAH 还原后，通过 Swern 氧化在自发的分子内醛醇反应和酮保护基裂解后得到烯酮 46。46 在回流四氢呋喃中，SmI(2) 介导的羰基-烯烃还原偶联反应顺利进行，得到五环中间体 49，用 2-碘代苯甲酸氧化，然后用三氟乙酸处理，得到（-）-GB 13。经过 19 个线性步骤，总收率为 6.1%。按照已知的程序，我们合成的（-）-GB 13 转化为 himgaline。此外，通过内酯 41 起始，首次实现了 gabulimima 生物碱家族中新分离成员（+）-GB 16 的全合成。该合成的特点是胺和 1,3-二酮部分之间的分子内缩合。
