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

Kuan Yu, Beiling Gao, Hanfeng Ding
2016 Huaxue xuebao  
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 CaCl 2 tube. The resulting mixture
more » ... e resulting mixture was stirred at 110 ℃ for 12 h before it was concentrated in vacuo. The residue was diluted with H 2 O, neutralized with NaHCO 3 (sat. aq.) and extracted with EtOAc. The combined organic layers were washed with brine, dried (Na 2 SO 4 ) 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 NaHCO 3 (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 H 2 O. The aqueous layer was extracted with CH 2 Cl 2 . The combined organic layers were washed with brine, dried (Na 2 SO 4 ) 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-Bu 3 SnH (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.].
doi:10.6023/a16020102 fatcat:no2yfuc75rfhxkq7v7xzpmnl4i