Barua A B, Olson J A
Biochim Biophys Acta. 1983 Jun 9;757(3):288-95. doi: 10.1016/0304-4165(83)90053-3.
All-trans retinoyl fluoride was prepared by treating all-trans retinoic acid with diethylaminosulfurtrifluoride. The crystalline product, which was characterized by melting point, infrared, 1H-NMR, 19F-NMR and elementary analysis, showed lambda max at 382 nm in hexane (epsilon = 4.98 x 10(4) M-1 . cm-1) and at 392 nm in methanol (epsilon = 4.60 x 10(4) M-1 . cm-1). Its biological activity in the rat growth assay, relative to all-trans retinyl acetate, was 22% +/- 10%. Upon oral administration for 5 days to vitamin A-depleted rats, retinoyl fluoride (1020 micrograms) was rapidly metabolized to a polar metabolite fraction and, in the intestine, to an unstable retinol-like metabolite, purportedly 15-fluororetinol. Upon administering intraperitoneally smaller doses (47-94 micrograms) of [11-3H]retinoyl fluoride, which was synthesized from [11-3H]retinoic acid, radioactive retinoic acid was noted in the liver and plasma but not in the intestine. As expected, a radioactive polar fraction appeared in the intestine and liver, but radioactive retinol, retinyl ester and some common oxidation products were not detected. Of the administered radioactivity, 72% was excreted in the urine, and only 4% was found in the feces over a 7-day period. Hydrolysis of the urine gave a radioactive fraction with a polarity similar to that of retinoic acid. Retinoyl fluoride also reacts readily with glycine to yield N-retinoyl glycine. Thus, the biological activity of retinoyl fluoride can be attributed to the formation of retinoic acid, probably by way of N-retinoyl derivatives. A possible pathway for its metabolism is presented.
全反式视黄酰氟是通过用二乙氨基三氟化硫处理全反式视黄酸制备的。该结晶产物通过熔点、红外光谱、1H-NMR（核磁共振氢谱）、19F-NMR（核磁共振氟谱）和元素分析进行表征，在己烷中λmax为382nm（ε = 4.98×10(4) M-1·cm-1），在甲醇中为392nm（ε = 4.60×10(4) M-1·cm-1）。在大鼠生长试验中，相对于全反式视黄醇乙酸酯，其生物活性为22%±10%。给维生素A缺乏的大鼠口服5天后，视黄酰氟（1020微克）迅速代谢为极性代谢物部分，并在肠道中代谢为不稳定的视黄醇样代谢物，据推测为15-氟视黄醇。腹腔注射较小剂量（47-94微克）由[11-3H]视黄酸合成的[11-3H]视黄酰氟后，在肝脏和血浆中检测到放射性视黄酸，但在肠道中未检测到。正如预期的那样，肠道和肝脏中出现了放射性极性部分，但未检测到放射性视黄醇、视黄酯和一些常见的氧化产物。在7天的时间里，所给予的放射性物质中，72%通过尿液排出，只有4%通过粪便排出。尿液水解后得到一个极性与视黄酸相似的放射性部分。视黄酰氟也能与甘氨酸迅速反应生成N-视黄酰甘氨酸。因此，视黄酰氟的生物活性可能归因于视黄酸的形成，可能是通过N-视黄酰衍生物的途径。文中提出了其可能的代谢途径。
