Research On The Synthesis Of Bergapten

Bergapten is an important linear furanocoumarin,and it is a natural product showing a wide range of biological properties.It is a potent photosensitizer of human skin,mollusk and microorganism and is used for the clinical treatment of psoriasis and vitiligo.Modern pharmacology tests show that it also has anti-hyperplasia and anti-tumor activities,so it's a potential intermediate to anti-tumor medication.Bergapten is also an applicable intermediate for the synthesis of more complex natural products.A simple method for the preparation of 4-Methoxy-7H-Furo[3,2-g][1]benzopyran-7-one was proposed in this paper,which is from phloroglucinol and ethyl propiolate by etherification,iodination,Pechmann condensation,coupling reaction,hydrolysis and decarboxylation.The proper technological parameters were ascertained by experiments.Under optimum conditions,n(phloroglucinol):n(anhydrous methanol)=1:15,catalyzed with HCl,reflex the mixture for three hours,the yield of phloroglucinol monomethyl ether was 53%;n(5-methoxybenzene-1,3-diol):n(I₂)=1:0.55,under ice bath,in 1.7mol·L^-1 H₂SO₄ solution,the reaction time was 15 min,the yield of 4-iodo-5-methox -ybenzene-1,3-diol was 81%;n(4-iodo-5-methoxybenzene- 1,3-diol):n(ethyl propiona -te)=1:3,catalyzed with ZnCl₂ 0.5g,N2,90℃for 2h,the yield of 7-Hydroxy-6- iodo-5- methoxybenzopyran-2-one was 58%; n(7-Hydroxy-6-iodo-5-methoxybenzopyran-2- one):n(ethyl propionate)=1:2,catalyzed with Cu₂O,N₂,110℃for 24h,the yield of 4-Methoxy-7oxidation-Furo[3,2-g][1] benzopyran-2-ether formyl was 63%;after hydrolysis,catalyzed with Cu,N₂,200℃for 2h, the yield of4-Methoxy- 7H-Furo[3,2-g][1]benzopyran-7-one was 75%.The structure of the synthetic products were characterized by Infrared Spectroscopy(IR),Mass spectra(MS) and ¹H Nuclear Magnetic Resonance(¹H NMR).The results proved that the structures and performance indexes of the products conformed to the design requirement and the synthesize way was novel and practical.