The Research On The Synthesis Of Retinoyl Flavonoid,Isoprenylamine And Sugar Derivatives

Retinoids contain natural vitamine A, their metabolites and all synthesized analogues. Study found that retinoids play an essential role in vertebrate growth and development, vision, supporting cell differentiation and embryonic development. Furthermore, it has been evaluated for their possible beneficial effects in several cancerous conditions.The actions of retinoids are mediated through binding and activation of the retinoic acid receptors (RARs) or retinoid X receptors (RXRs), which function as ligand-dependent transcription factors. Unfortunately, Retinoids, including retinoic acids, have been found to be too toxic at high dosage levels to be of practical value for cancer prevention in higher mammals. Therefore development of retinoid analogues possessing a higher therapeutic index is of interest.Flavonoids are a kind of natural organic compounds with potential physiological activities and effective components of Chinese Herbs. Solanesol is a high added value product which has remarkable medical effects such as diminishing inflammation, hemostaria and antibacterial. Nitrogen mustard is not a single-structure anti-tumour group, the dissociated and the conjugation with other compounds are both anticancer prodrugs. Carbohydrates are a large group of biomolecules which are distributed widely in nature and involved in a great variety of physiological and pathological processes. In order to decrease toxicities of retinods and enhance pharmacal effects and gain the relative derivatives with better curing effect and selectivity. The work we have done are displayed:First, Synthesized 7-Hydroxy- Flavonoe by improved Bake-Venkatarama method. Retinoic acid was modified by changing the polar group, After investigating various reaction conditions, a new synthetic method with mild reaction conditions was built up to synthesize retinoates. With dicyclohexylcarbodiimide (DCC) as reagent and 4-dimethylaminopyridine (DMAP) as catalyst, a series of retinoates were synthesized from all-trans-retinoic acid and 13-cis-retinoic acid. The method was proved to be relatively simple and stable with high yields and superior practical value.Second, Retinoic acid was modified by using solanesolamine group. In order to improve the therapeutic efficacy of retinoid carboxylic acids, a novel retinoate was designed and synthesized with 4-aminophenol as a linker from solanesol and 4-Carbonyl-13-cis-retinoic acid. Which is one of much polar metabolites of 13-cis-retinoic acid in plasma. Third, Retinoic acid was modified by use of sugar, and hydroquinone as bridge. A mild selective method for deacetylation has been developed. It's application to deacetylation of glucosides was studied using catalytic amount of dibutyltin oxide ascatalyst and methanol as solvent. The mechanism of the deprotection reaction have been discussed. The present results showed that the method is suitable for deactylation of glycoesters. The method has advantages of mild reaction conditions, easy seperation of products and high stereospecificity.We have synthesized 22 compounds and 10 of them were not reported in literatures until now. Their structures were characterized and confirmed by IR, 1H NMR, 13C NMR and MS spectra.