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为寻找新型的PPAR激动剂,本研究以L-酪氨酸为起始原料,经过羧基酯化、氨基酰胺化、酚羟基溴烷基化及溴烷基胺基化等多步反应,成功合成了20个含苯氧乙酰基结构单元的L-酪氨酸衍生物TM1(总收率21%~75%);TM1碱性水解,得到16个相应的水解产物TM2(77%~99%)。共得到4个中间体和36个目标化合物,其中39个新化合物的结构得到1H NMR、13C NMR证实,35个新化合物进一步通过HR-MS确证。体外抗糖尿病活性结果表明,目标化合物的PPAR相对激动活性整体较弱,最高者TM2i为50.01%,需要进一步改进。
In order to find a novel PPAR agonist, L-tyrosine was used as the starting material to synthesize PPAR agonist successfully. After carboxyl esterification, amino amidation, phenolic hydroxy bromide alkylation and bromoalkylamination, 20 L-tyrosine derivatives TM1 with phenoxyacetyl structural units (21% -75% of the total yield) were obtained. Alkaline hydrolysis of TM1 gave 16 corresponding hydrolyzate TM2 (77% -99%), . A total of 4 intermediates and 36 target compounds were obtained. The structures of 39 new compounds were confirmed by 1H NMR. 13C NMR confirmed that 35 new compounds were further confirmed by HR-MS. The anti-diabetic activity in vitro showed that the relative activity of PPAR of the target compounds was weak as a whole. The highest TM2i was 50.01%, which needed further improvement.