.5 - Methoxy Psoralen (5-mop) Synthesis

Furanocoumarins are natural products showing a wide range of biological properties. Many are effective with anti-coagulating, bactericide, antivirus, anti-hyperplasia, anti-tumor, anti-infectious and anti-HIV. So the chemistry of furanocoumarin derivatives has received much attention.Bergapten, linear furanocoumarin, is a potent photosensitizer of human skin, mollusk and microorganism and be 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.In this dissertation, the synthesis ways of furanocoumarins were studied, and a new synthesis route to bergapten was designed 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 and the feasibility of route to linear furanocoumarins by regioselective iodination, Pechmann condensation and coupling reaction was studied. Under optimum conditions, the amount of phloroglucinol was 40g, the volume of methanol was 200mL, gaseous HCI as catalyst, reflux for 3h, the yield of phloroglucinol monomethyl ether was 55%; Under ice bath, in 1.7mol·L^-1 H₂SO₄ solution, n(5-methoxybenzene-1,3-diol) : n(I₂) =1:0.55, the reaction time was 15 min, the yield of 4-iodo-5-methoxybenzene-1,3-diol reached about 81%; Under N₂, n(4-iodo-5-methoxybenzene-1,3-diol) : n(ethyl propiolate) : n(ZnCl₂)=1:3:1.1, the mixture was heated at 90℃for 1.5h , the yield of 7-hydroxy-6-iodo-5-methoxy-2H-chromen-2-one reached about 57.7%; Under N₂, n(7-hydroxy-6-iodo-5-methoxy-2H-chromen-2-one) : n(ethyl propiolate) : n(Cu₂O) =1:1.6:0.7, the mixture was heated at 110℃for 36h , the yield of ethyl 4-methoxy-7-oxo-7H-furo[3,2-g]chromene-2-carboxylate was 61.9%; Alkaline hydrolysis of ethyl 4-methoxy-7-oxo-7H-furo[3,2-g]chromene-2-carboxylate and subsequent decarboxylation by treatment with copper power in quinoline ,the yield of bergapten was 74.7%.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.