Studies on the Development of Medications for Treating Osteoporosis:Synthesis of β-(p-((N-Alkanoylprolyl)amino)benzyl) D-Glucosaminepyranoside with Various Length of Alkanoic Acids and Its Biological Activity

• Main Authors: Yen-Yu Lin, 林晏右
• Other Authors: Yow-Fu Tsai
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/60156381378013131761

碩士 === 中原大學 === 化學研究所 === 101 === Glycolipid compounds GPS-1 (18), GS (18), and GO (18) synthesized in our laboratory , we found that GPS-3 (18) than the other two high GS (18) and GO (18). After comparing the three structural differences, we GPS-1 (18) is the lead compound (lead compound), Synthesized a series ofsaturated fatty acids with differrent carbon number of glycolipid compoundsGPS-1 series, explore a systematic relationship between the structure andbiological activity (structure-acti- vety relationship, SAR). GPS-1 series of compounds is N-acetyl glucosamine (glucosamine) as a starting material, via a plurality of oxide acetylation (per-O-acetylation), cyclization reaction (cyclization), glycosylation reaction (glycosylation) , N-tertiary-butoxycarbonyl-amidation reaction (amidization) and the hydrogenation reaction (hydrogenation) and other five steps to prepare the compound GS-5.Compound GS-5 and then with FMOC-L-proline (Fmoc-L-Proline) conductedamidation reaction (amidization), then de 9-fluorenyl methoxycarbonyl(fluorenylmethyloxycarbonyl, Fmoc) reacts with different unsaturated carboxylic acid amide having a carbon number of the amination reaction, and thedeacetylation reaction to tert-butoxycarbonyl (t-butyloxycarbonyl, Boc) reaction, the five-step reaction to obtain the target GPS-1. Activity test parts: for a single dose (10 μM) of the activity test, we found thispart of a series of compounds has a significant inhibitory effect, but some with no apparent biological significance, and not because of the length of the carbon chain showed a correlation , visibility, influence the activity of the carbon chain is not the main reason. In addition, we have also done a multiple dose (10,20,30 μM) activity test and found that this series of compounds at concentrationsincrease, the correct time will increase its inhibitory activity.