文档介绍：湘潭大学
硕士学位论文
香豆素类抗凝血药华法林及其类似物的合成
姓名:刘小帆
申请学位级别:硕士
专业:应用化学
指导教师:申东升;邓建成
20050501
Coumarin anticoagulants, called oral anticoagulant are a
pharmaceutical taken orally to participate intravital metabolism. Varities
had been applied to clinic such as dicoumarol or ethyl biscoumacetate,
warfarin(benzyl acetone coumarin) and acenocoumarol(4-nitrobenzyl
acetone coumarin also called nicoumalone). Dicoumarol is usually
shared with heparin, because it was absorbed slowly as taken orally. On
the countrary, warfarin and acenocoumarol were absorbed rapidly and
completely as taken orally. Their concentration in blood will reach the
pinnacle within 2-4 hours. The characteristics of lasting continuance and
high biologic utilization made them especially adaptive to those who
must maintain anticoagulation long-term. Presently, the numbers of
people with thrombophlebitis, pulmonary and myocardial infarction
are increased sharply, while domestic demand to warfarin has mainly
been depending on importation. Therefore, high- yield and economical
synthesis for pound was evident.
Our study began from the synthesis of substituted benzaldehyde
explored the best routes. Eight substituted benzalacetone were prepared
via the improvement of technics of benzalacetone, The products were
proved by IR, 1H NMR.
Then, warfarin and its analogs acenocoumarol, 4-hydroxybenzyl
acetone coumarin, 4-methoxybenzyl acetone coumarin, 4-chlorbenzyl
acetone coumarin, 4-butylbenzyl acetone coumarin, thiofuran acetone
coumarin, furan acetone coumarin was synthesized by Michael addition
reaction of 4-hydroxycoumarin and substituted benzaleacetone without
any catalyst. The yield were all more than 60%. The products were
proved by IR, 1H NMR. The factors affected the reaction were
investigated. This procedure was simple with easy final-treatment,
seems to be amenable to large-scale application.
We got a better result by the improvement of synthesis