The Total Synthesis Of Four Coumarin Natural Products

The total synthesis of coumarin class of natural products has become aresearch hotspot in recent years, due to its good anti tumor, anti HIV, antioxidant,anti-inflammatory, antibacterial and other aspects of the biological activities. Inthis thesis, we started from simple small molecules, completed the total synthesisof four coumarin natural products extracted from monoterpene.1.The preparation of the intermediate (1S,5R)-5-(hydroxyl-methyl)-4,6,6-tri-Methylcyclohex-3-enol M1: We got the M1from the SM of (E)-3,7-dimethylocta-2,6-dien-1-ol, through the protection of carboxyl, doublehydroxylation, epoxidation and ring closing reaction. We used TsCl instead ofhighly toxic and cancerigenic reagent MsCl in epoxidation. In this paper, theyield was62.7%, while the literature yield is51.5%.2.The preparation of the intermediate (7-substituted coumarins) M2: In thispaper,7-bromide-coumarin(3-1) is obtained by malic acid and3-bromine phenolas raw material by coupling cyclization reaction,7-iodine-coumarin(3-2) isobtained by malic acid and3-iodine phenol as raw material by couplingcyclization reaction. five7-substituted of coumarin compounds synthetisedthrough reduction, P-toluene sulfonyl protection by7-hydroxy coumarin as rawmaterial,they are named7-bromochroman-2-one(3-3),7-hydroxy-chroman-2-one(3-4),2-oxochroman-7-yltrifluoromethanesulfonate(3-5),2-oxo-2H-chromen-7-yltri-fluoromethanesulfo-nate(3-6),2-(benzyloxy)-4-bromobenzaldehyde(3-7).3.The preparation of natural product (E)-7-((3,7-dimethylocta-2,6-dien-1-yl)Oxy)-2H-chromen-2-one(A): natural product A is obtained by the coupling of (E)-3,7-dimethylocta-2,6-dien-1-ol and7-hydroxy coumarin directly, and the yieldwas30.0%.4.The preparation of natural product(S,E)-7-((5-(3,3-dimethyloxiran-2-yl)-3- methylpent-2-en-1-yl)oxy)-2H-chromen-2-one(B): natural product B is obtainedby the coupling of (S,E)-5-(3,3-dimethyloxiran-2-yl)-3-methylpent-2-en-1-ol and7-hydroxy coumarin directly, and the yield was67.4%.5.The preparation of natural product7-(((1R,5S)-5-hydroxy-2,6,6-tri-methylcyclohex-2-en-1-yl)methoxy)-2H-chromen-2-one(C): natural product is obtainedC from the intermediate A and intermediate B as raw material, cuprous iodide asoxidant,1,10-phenanthroline as ligand, in the presence of cesium carbonateunder the condition of160degree sealed reaction for24h.6.The preparation of natural product (1S,5R)-4,6,6-trimethyl-5-(((2-oxo-2H-chromen-7-yl)-oxy)-methyl)-cyclohex-3-en-1-yl-3-methyl-butanoate(D): thenatural product D is obtained from the natural product C and isoamyl chloride asraw materials by esterification reaction, and the yield was62.5%.In the previous literature, the natural product C only reported the1H-NMRspectrum, and compound D with another kind of natural product mixtures ofhydrogen spectrum and carbon spectrum. This paper successfully obtained singlecompound D by chemical synthesis, and the structures of these compounds werecharacterized by1H-NMR，13C-NMR，MS and other means of detection.