| Fibrauretine is a natrual protoberberine alkaloid extracted from a Chinese herbal medicine Berberidaceae.It exhibits a wide variety of pharmacological and biological activities such as anti-bacteria,anti-fungi and anti-vinuses.And it has been widely used to treating various inflammatory diseases,such as surgical infection,bacillary dysentery, eneritis,peogaster,respiratory tract and urinary tract infection,pink eye and gynecological inflammation etc.The Fibrauretine medicaments have wide range of applications and exact efficacy in clinic,and it's in short supply.Owning to the long growth cycle of berberidaceae plants and short supply of natural fibrauretine,studies on the synthesis of Fibrauretine alternatives to natural Fibrauretine to alleviate the increasingly shrinking medicine resources is currently a better solution. At present, a number of domestic pharmaceutical companies have developed sevral synthetic routes of Fibrauretine, or the reduction of material fibrauretine tetrahydropalmatine line and they attempted to industrialized,but the synthetic route reported suffer from too long, the yield is not high, as well as the synthesis with large environmental pollution,high cost and other issues.The development of a new and effective synthetic route has great market and research value.In this work, a new route for the synthesis of fibrauretine was developed starting from catechol, the synthetic route involves catechol methoxylation gets 1.2-dimethoxybenzene (yield:90.5%),via vilsmeier reaction gets 3,4-dimethoxybenz- aldehyde(yield:95.2%),via henry reaction gets 3,4-dimethoxy-β-nitrostyrene (yield:93.6%), KBH4/F3B-Et2O catalytic synthesis of 3,4-dimethoxyphenylethy- lamine(yield:87.5%),condensation gets Schiff base then reduction by KBH4 gets N-(2,3–dimethoxybenzyl)-β-(3,4-dimethoxybenzyl)ethylamine (yield:87%),re-cond- ensation gets the end product Fibrauretine(yield:85%) in overall yields of 52.2%.Reaction conditions were optimized,the intermediates and end product were analysised.This thesis provided a key step via Henry reaction from 3,4-dimethoxybenzald- ehyde and niro-methane synthesis of 3,4-dimethoxyphenyl-β-nitro-ethylene,and KBH4/F3B-Et2O catalyzed 3,4-dimethoxyphenyl-β-nitro-ethylene reduction generates 3,4-dimethoxy-phenylethylamine in new methods.Throughout the synthesis process, not only the raw materials used in low-cost are easy to get,but also the post-processing of intermediate and end product is simple to deal with.and pilot experiments laid the foundation for the expansion. |
