Study Of Green Synthesis Techniques Of 13-cis-retinoic Acid And Vitamin A Acetate

Vitamin A was one of essential nutritive factors for human being.Vitamin A acetate had wide range of physiological effect and application value,such as sustaining visual process,human immunity,promoting development and so on.Therefore,they were in great demand in pharmaceutical industry,cosmetics,health care products etc.More importantly,retinoic acid had been demonstrated to be highly effective in inhibiting chemically induced carcinogenesis and tumor.In fact,many RA isomers had been recognized as cancer therapeutic agents clinically in the treatment of different kinds of tumors.Currently,traditional methods utilized for the synthesis of retinoids,however,needed too many reaction steps and also were accused of asking high technological requirements and getting low yields.Whereas,mild reaction conditions and low cost featured Horner-Wadsworth-Emmons reaction based on phosphonate was adopted to the construction of this polyene side chain.In the preparation of key intermediate ?-ionone,synthetic performance was greatly improved by an innovative combination of self-prepared polymer-bound secondary amine catalyst and microwave-assisted organic synthesis.And the yield was above 80%.Notably,the heterogeneous catalyst could be reused four times without significant loss of its reactivity,all of which laid a solid foundation of the ggreen synthesis of ?-ionone.In the synthesis of the two C5 synthons,as for furanome,by screening many different kinds of secondary amine salt used for the mannich reaction,the yields got remarkable increase,which was 92%.For C5 aldehyde,convenient nitroacetoxylation method was favored,also,its raw materials were very easy to get.The optimum substrate equivalent of nitroacetoxylation reaction was investigated,which was followed by the attempt to find an excellent alternative reaction condition of Nef reaction.Stannous chloride was tested to be the best reagent in this transformation.It was proven the yield of this synthon was above 60%.Meanwhile,the rather time-consuming synthetic method of the other vital intermediate tetraethyl methylenediphosphonate was totally altered,yield was improved to 78%.Thus,one of the tightest bottlenecks of the collective synthetic routine was overcome.Finally the two target compounds were synthesized by HWE reaction,optimum reaction conditions were achieved by comparing different solvent and base.All in all,after a series of inquiries and trials,the synthetic performances of 13-cis-retinoic acid and retinol acetate based on HWE reaction were improved as a whole.These endeavors will be good reference for other studies on the synthesis of retinoids.