治療骨質疏鬆症藥物的開發研究： 具不同碳數飽和羧酸的β-(對-((N-烷醯脯胺醯)胺基) 苄基)D-葡萄糖胺苷的合成及其生物活性

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

林晏右(Yen-Yu Lin)

指導教授 ： 蔡祐輔

中原大學/理學院/化學研究所/碩士(2013年)

https://doi.org/10.6840/cycu201300951

摘要

本研究室合成醣脂質化合物GPS-1 (18)、GS(18)與GO(18)，在將其進行骨質疏鬆症生物活性篩選後，我們發現GPS-3(18)較其他兩者高。比較三者結構差異後，我們以GPS-1(18)為先導化合物(lead compound)，合成一系列具有不同碳數飽和脂肪酸之醣脂質化合物GPS-1系列，以有系統探討結構與生物活性關係(structure -activity relationship, SAR)。
GPS-1系列化合物是以N-乙醯葡萄醣胺(glucosamine)作為起始物，經由多氧乙醯化反應 (per-O-acetylation)、環化反應 (cyclization)、醣苷化反應 (glycosylation)、N-第三丁氧羰基醯胺化反應 (amidization)及氫化反應 (hydrogenation)等五步反應，製得化合物GS-5。化合物GS-5再與芴甲氧羰基-L-脯氨酸(Fmoc-L-proline)進行醯胺化反應(amidization)後，再進行去9-芴甲氧羰基(fluorenylmethyloxycarbonyl, Fmoc)反應與不同碳數飽和羧酸之醯胺化反應、去乙醯化反應及去叔丁氧羰基 (tert-butyloxycarbonyl, Boc)反應，經五步反應製得到目標物GPS-1。
活性測試部份：進行單一劑量(10 μM)的活性測試後，發現此一系列化合物部份具有顯著抑制的效果，但部份卻沒有明顯的生物意義，且並沒有因為碳鏈長短呈現一個相關性，可見碳鏈並不是影響活性的主因。另外，我們也做了多重劑量(10、20、30 μM)的活性測試，發現此一系列化合物在濃度增加後，確時都會增加其抑制活性。

關鍵字

D-葡萄糖胺苷 ； 骨質疏鬆症 ； 醣脂質化合物

並列摘要

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.

並列關鍵字

Osteoporosis ； Glycolipid ； D-Glucosaminepyranoside

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