The Synthesis Of Coleonolic Acid Intermediates

Numerous studies show that Forskolin Coleus of the main chemical composition is the sesquiterpenes, triterpenes, flavon-oids and steroidal.Pharmacology research has testified its widespread pharmacological effects,such as asthma antispas-modic effect,reducing intraocular pressure, inhibiting of platelet aggregation and antitumor role. Professor Yan wen Liu published patent CN200610019675to prove that Coleus forskohli i’s main chemical compositions is diterpene types, and they can also proved Coleonolic acid,Coleolic acid and Colex-anthone inhibit the tumor growth and proliferation through screening the cell activity and they are diterpenes types. Forskolin has successfully developed a class of drugs for the diterpenoid and it has a good effect on heart failure, glaucoma, bronchial asthma.Purpose of the experiment:Related patents proved that the Coleus acid inhibit tumor cell growth. The workload is considerable to extract and separate from Coleus fors kohlii by taking into account the extremely limited Coleonolic acid. From the research point of view of domestic and foreign, Chemical synthesis had been reported very seldom.We act Coleonolic acid for the target compounds and research the route of synthesis. Because the Sclareol can be attained easily and has mild reaction conditions, we choose the starting material of sclareol.We provide raw materials from chemical synthesis the intermediate of Coleonolic acid and its analogs, which can be modified and activity screening and construct two terpenoids synthesis research platform.Experimental methods and results:1The synthetic route:Sclareol as raw materials is oxidized by neutral potassium permanganate can produce Methyl ketone compounds (2) in room temperature; Methyl ketone compounds (2) is oxidized for carboxylic acid compounds (3) in glacial acetic acid under acidic conditions. Carboxylic acid compounds (3) in LTA/I2system and solar light, heating, carboxyl was iodine replaced by generating at least one carbon Iodine compounds(TM1). Sclareol as raw materials, chromium trioxide as oxidant, acetic anhydride to do a dehydrating agent, acetic acid conditions, which is heated to generate Sclareolide. Borohydride k/zinc reductive into alcohol compound (compounds5)。 Sclareol as raw material, at room temperature, neutral potassium permanganate oxidation of Methyl ketone compounds(2), Methyl ketone compounds (2) in the weak acid acetic acid heating conditions to generate enol ether.2Process optimization:The article to the synthetic Methyl ketone compound (2) and Iodine compound(TM1) from the mol ratio, reaction temperature, reaction time were investigated and after that we choose the best synthesis conditions. Orthogonal design of synthetic carboxylic acid compound (3) to select the optimum reaction conditions and optimize the synthesis process. Experimental conclusions:1.The Products can be testified by IR,1H-NMR,13C-NMR, map resolution. The map can show that several intermediates has been prepared successfully2. In this paper, synthetic Methyl ketone compound (2) and the compounds of Iodine compound(TM1) affect the reaction of the conventional factors such as time, temperature, feed ratio were investigated in detail. The Methyl ketone compound(2) after only a simple filtration, followed by next reaction, time is shorten and costs is reduced, production rate is increased. Carboxylic acid compound(3)is used in the orthogonal design, the mol ratio, reaction temperature, reaction time, the four factors and three levels orthogonal design get the better of the synthesis conditions.The article successfully applied Nobel Prize winner by Barton name reactions, the reaction is guidanced from the reaction mechanism of conventional factors such as mol, LTA, reaction temperature, reaction time, the synthesis yield of TM1make us get satisfactory results.