化学学报 ›› 2016, Vol. 74 ›› Issue (5): 410-414.DOI: 10.6023/A16020102 上一篇    下一篇

研究通讯

吲哚生物碱(+)-Alsmaphorazine D的不对称全合成及其绝对构型更正

余宽, 高北岭, 丁寒锋   

  1. 浙江大学化学系 杭州 310028
  • 收稿日期:2016-02-25 出版日期:2016-05-15 发布日期:2016-04-08
  • 通讯作者: 丁寒锋 E-mail:hfding@zju.edu.cn
  • 基金资助:

    项目受国家自然科学基金(No. 21472167)及浙江省杰出青年基金(No. LR16B020001)资助.

Asymmetric Total Synthesis and Absolute Configuration Reassignment of Indole Alkaloid (+)-Alsmaphorazine D

Yu Kuan, Gao Beiling, Ding Hanfeng   

  1. Department of Chemistry, Zhejiang University, Hangzhou 310028
  • Received:2016-02-25 Online:2016-05-15 Published:2016-04-08
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 21472167) and the Zhejiang Natural Science Fund for Distinguished Young Scholars (No. LR16B020001).

通过无痕手性转移策略实现了(+)-alsmaphorazine D的首次不对称全合成, 并对其绝对构型进行了更正. 该高效合成路径的关键步骤主要包括催化氧化环合反应、非对映选择性氧化缩醛胺化环合反应以及分子内自由基环合反应.

关键词: 生物碱, 全合成, 四环体系, 氧化环合, 自由基反应

The first asymmetric total synthesis of (+)-alsmaphorazine D has been achieved through a traceless chirality transfer strategy, which also enabled absolute configuration reassignment of the natural product. Key steps of this efficient approach entail a catalytic oxidative cyclization [To a solution of indoline ester 8 (5.82 g, 10 mmol) in AcOH (100 mL) were added CAN (550 mg, 1 mmol) and NaOAc (1.64 g, 20 mmol). The reaction vessel was exposed to air through a CaCl2 tube. The resulting mixture was stirred at 110 ℃ for 12 h before it was concentrated in vacuo. The residue was diluted with H2O, neutralized with NaHCO3 (sat. aq.) and extracted with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4) and concentrated in vacuo. Flash column chromatography (silica gel, hexanes/EtOAc, V:V=4:1) afforded δ-lactamindole 7 (4.34 g, 75%) as a white amorphous solid], a diastereoselective oxidative cyclic aminal formation [To a stirred solution of mono-ester 13 (5.20 g, 10 mmol, dr=1:1) in acetone (100 mL) at 0 ℃ was added NaHCO3 (100 mL, sat. aq.). The resulting mixture was stirred for 0.5 h before it was added oxone (12.28 g, 20 mmol) slowly. The reaction mixture was stirred at 0 ℃ for an additional 2 h before it was diluted with H2O. The aqueous layer was extracted with CH2Cl2. The combined organic layers were washed with brine, dried (Na2SO4) and concentrated in vacuo. Flash column chromatography (silica gel, hexanes/EtOAc, V:V=3:1) afforded pyrroloindole 6' (1.61 g, 71%) as a white amorphous solid] and an intramolecular radical cyclization [To a stirred solution of ent-5 (250 mg, 0.47 mmol) in benzene (5 mL) at 80 ℃ were added n-Bu3SnH (152 μL, 0.56 mmol) and AIBN (5 μL, 0.047 mmol). The resulting mixture was stirred for 0.5 h before it was concentrated in vacuo. Flash column chromatography (silica gel, hexanes/EtOAc, V:V=1:1) afforded C(16)-epi-ent-4 (213 mg, 72%) as a colorless oil.].

Key words: alkaloid, total synthesis, tetracyclic system, oxidative cyclization, radical reaction