The Research On The Synthesis Of Retinoyl Sugar And Isoprenylamine Derivatives

Retinoic acid is nonsteroidal small molecule hormone and plays a key role in the maintenance and differentiation of epithelial tissue and is very important for the treatment of acne and skin damaged by UV-light. 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.Carbohydrates are a large group of biomolecules which are distributed widely in nature and involved in a great variety of physiological and pathological processes. 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. Sugar and isoprenylamine modification can decrease the toxicity and increase absorption of some nature drugs. Nowadays, synthesis of sugar compounds to modify nature drugs has become an important field of pharmaceutical chemistry. 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, 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 use of sugar, Four new glucosyl esters of all-trans-acitretin were synthesized by the reaction of all-trans-acitretin with O-acetylglucopyranosyl bromide or O-acetylgalactopyranosyl bromide, O-acetylgalactopyranosyl bromide, O-acetylgalactopyranosyl bromide in the...