SYNTH & BIOL ACT OF TRANS RETINOL METABOLITE PRODUCE THRU NEW RETINOL METAB PATH

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。视黄醇及其代谢产物参与许多生理过程，如生长、发育、繁殖、细胞分化和视觉。饲喂不含视黄醇和全反式视黄酸（全反式视黄酸，atRA）饲料的大鼠无法繁殖。已有研究表明，维生素A缺乏、atra补充（VAD-RAS）的雌性大鼠不迟于妊娠第10天就需要视黄醇，以防止胎儿吸收。在维生素A缺乏、维甲酸补充的第10天大鼠体内对所有反式视黄醇的代谢研究导致了一种新的代谢物的分离和鉴定，即2-（羟甲基）-3-甲基-5-（2′-氧丙基）-2,5-二氢噻吩的异构体。在继续我们对这种代谢物的生物学研究中，我们合成了代谢物的顺式和反式异构体。这些最终异构体及其前体的构型将通过1H、1H COSY二维光谱和1H NOE差谱来确定，并与自然存在的异构体进行比较。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Retinol and its metabolites participate in many physiological processes, such as growth, development, reproduction, cellular differentiation, and vision. Rats fed with retinol-free and all-trans-retinoic acid (atRA)-supplemented diet fail to reproduce. It has been shown that retinol is required no later then day 10 of gestation in order to prevent fetal resorption in the vitamin A deficient, atRA-supplemented (VAD-RAS) female rats. Metabolic studies on all trans retinol in day 10 conceptuses of vitamin A deficient, retinoic acid supplemented rats led to the isolation and identification of a novel metabolite, the isomers of 2-(hydroxymethyl)-3-methyl-5-(2'-oxopropyl)-2,5-dihydrothiophene. In continuation of our biological studies of this metabolite, we synthesised the cis and trans isomers of the metabolite. Configurations of these final isomers as well as their precursors are to be determined by 1H, 1H COSY 2D spectra and 1H NOE difference spectroscopy to compare th e isomers with the naturally occuring ones.