苯并呋喃与苯并二氧六环类新木脂素及其衍生物的合成与生物活性研究

以3,4-二羟基苯丙烯酸(咖啡酸)为原料,经酯化和仿生氧化偶联反应得到苯并呋喃类化合物2-(3′,4′-二羟基苯基)-3-甲氧羰基-5-甲氧羰基乙烯基-7-羟基-2,3-二氢苯并呋喃(1)和苯并二氧六环类化合物2-(3′,4′-二羟基苯基)-3-甲氧羰基-6-甲氧羰基乙烯基-2,3-二氢-1,4-苯并二氧六环(2),然后经乙酰化、DDQ氧化脱氢、Pd/C催化氢化、氢化铝锂还原、碱性条件下脱乙酰基等反应,合成了一系列苯并呋喃新木脂素类化合物3~7和苯并二氧六环新木脂素类化合物8~10.所合成化合物的结构已由核磁共振法(1 H NMR,13 C NMR)、质谱法(MS)进行了表征.其中5~7,9和10是未见文献报道的新化合物,8为天然产物异美商陆醇A.采用MTT法对所合成的苯并呋喃新木脂素类化合物1,3~5进行了生物活性测试.结果表明:化合物1,3,4和5对白血病细胞(HL-60)、肺癌细胞(A-549)、乳腺癌细胞(MCF-7)、结肠癌细胞(SW-480)、肝癌细胞(SMMC-7721)有良好的体外生长抑制活性.

Synthesis and Biological Activity of Benzofuran and Benzoxioxane Neolignans Compounds

Benzofurans compound 2-(3',4'-dihydroxyphenyl)-3-methoxy carbonyl-5-methoxy carbonyl vinyl-7-hydroxy-2,3-dihydrobenzofuran (1) and benzodioxanes compound 2-(3',4'- dihydroxyphenyl)-3-methoxy carbonyl-6-methoxy carbonyl vinyl-2,3-dihydro-1,4-benzodioxane (2) were synthesized from caffeic acid through esterification and biomimetic oxidative coupling reactions. Moreover, a series of benzofuranneolignan compounds 3~7 and benzodioxaneneolignan compounds 8~10 were synthesized from compounds 1 and 2 respectively through acetylation, DDQ oxydehydrogenation, Pd/C catalytic hydrogenation, lithium aluminium hydride reduction and deacetylation in alkaline condition. All of these synthesized compounds were confirmed with MS, IR, 1H NMR and 13 C NMR spectra. Among them, 5~7,9 and 10 are new compounds. 8 is the natural product isoamericanol A. The biological activities of benzofuranneolignan compounds 1, 3~5 against five human cancer cell lines were evaluated in the standard MTT method, and the results have shown that compounds1, 3, 4 and 5 exhibit good inhibitory effect on leukemia cells (HL-60),lung carcinoma cell (A-549), breast cancer cell (MCF-7), colon cancer cell (SW-480), and hepatoma carcinoma cell (SMMC-7721).