研究目的
To develop a non-toxic free-radical approach for the stereoselective synthesis of (+)-muscarine using photoredox decarboxylation and tin-free Barton-McCombie reactions.
研究成果
A non-toxic free-radical synthesis of (+)-muscarine was successfully developed, featuring a novel strategy for installing the C-5 methyl group via photoredox decarboxylation and tin-free deoxygenation. This approach provides a new method for accessing biologically important C-methyl glycosides and highlights the potential of photoredox chemistry in alkaloid synthesis.
研究不足
The photoredox catalysts were ineffective for some radical deoxygenation steps, requiring alternative methods like Et3B/O2 conditions. Optimization efforts for certain reactions were unsuccessful, and some byproducts could not be isolated with high purity.
1：Experimental Design and Method Selection:
The synthesis utilized a chiron approach starting from a 1,2-O-isopropylidene-D-xylofuranose derivative. Key methods included stereoselective nucleophilic substitution at the anomeric position (NSAP), blue-light photoredox decarboxylation, and tin-free Barton-McCombie deoxygenation.
2：Sample Selection and Data Sources:
The starting material was a dibenzylated D-xylofuranose derivative.
3：List of Experimental Equipment and Materials:
Equipment included a blue-LED light source, a 150 W tungsten lamp, and standard laboratory glassware. Materials included allyltrimethylsilane, BF3?OEt2, tert-butyldimethylchlorosilane (TBSCl), N,N’-dicyclohexylcarbodiimide (DCC), 4-dimethylaminopyridine (DMAP), 2-mercaptopyridine N-oxide, N-hydroxyphthalimide, Ir[dF(CF3)ppy]2(dtbbpy)PF6 catalyst, Hantzsch ester, Ru(bpy)3(PF6)2 catalyst, Pd(OH)2, 1,1’-thiocarbonyldiimidazole (TCDI), triethylborane, tosyl chloride, and BF3?OEt
4：Experimental Procedures and Operational Workflow:
Steps involved allylation to form C-glycoside, protection with TBSCl, ozonolysis/Pinnick oxidation to carboxylic acid, formation of ester Barton and N-acyloxyphthalimida derivatives, photoredox decarboxylation with blue-LEDs, debenzylation, formation of cyclic thiocarbonate and acyclic thionocarbamate, radical deoxygenation using Et3B/O2 conditions, deprotection, and substitution to yield (+)-muscarine.
5：Data Analysis Methods:
Products were characterized using NMR spectroscopy, and yields were calculated based on isolated products after column chromatography.
独家科研数据包，助您复现前沿成果，加速创新突破
获取完整内容
