Research On The Synthesis And Characterization Of 13-cis-Retinoic Acid Derivatives Containing N, O-Funcitons

Retinoids contain natural vitamine A, their metabolites and all synthesized analogues. Study found that retinoids play an essential role in vertebrate growth and development, supporting cell differentiation, embryonic development, vision, the immune response and reproduction. All-trans-retinoic acid (ATRA), 13-cis-retinoic acid (13-c-RA) as well as other retinoids are currently used for treatment of dermatological disorders and certain types of cancer. The actions of retinoids are mediated through binding and activation of the retinoic acid receptors or retinoic acid X receptors, 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.Results of bioactivity showed that many retinoates and retinamides can reduction of wrinkling of the skin as an incident of aging and actinic damage, used for treatment of skin diseases, breast cancer, and the side effect is less than 13-c-RA. So we guess the toxicity is possibly due to the strong carboxylic polarity. In order to decrease toxicities of 13-c-RA and enhance pharmacal effects and gain the relative derivatives with better curing effect and selectivity, structures of 13-c-RA were modified by nitroalkenes, Schiff bases and neolignans. Three major sections are involved in this thesis.In the first section, a series ofα-nitryl phenyl propene derivertives were synthesized from aldehydes and nitroethane with ammonium acetate/acetic acid as solvent and ammonium cetyltrimethyl bromide as the phase transfer catelyst. The productions reacted with 13-c-RA under protecting with N2, avoiding light and stirring conditions and three 13-cis-retinoates containing nitroalkene corresponding were obtained. Selected reductioned of double bonds which are joined nitryl by sodium borohydride, and three other 13-cis-retinoates 10a~10c were obtained.In the second section, 13-c-RA esterified with substituent hydroxybenzenes (or 4-hydroxyl aniline), the products reacted with 4-amidoantipyrine (or aldehyde) and eight of Schiff base-13-cis-retinoates were obtained. The crystal of 11a was obtained and determined by single crystal X-ray diffraction analysis and its molecular structure has been confirmed. Compound 11a belongs to monoclinic system with space group P2 (1) /c, a = 22.235 (3) ?, b = 7.4117 (10) ?, c = 15.990 (2) ?,β= 109.253 (3)°, V = 2487.7 (6) ?3, Z = 4, R = 0.0613, wR = 0.01437, GOF = 0.814.In the last section, neolignans 16a, 16b were synthesized via Knoevenagel reaction, esterification and Ag2O-catalyzed biomimetic oxidative coupling from vanillin or...