CN108658911B - 一种呋喃萘醌类化合物及其制备方法 - Google Patents
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Abstract
本发明属于医药技术领域，具体涉及从镰刀霉属植物内生微生物代谢产物中提取得到一种新的呋喃萘醌类化合物fusarnaphthoquinones D及其制备方法；本发明以采集自长白红景天（Rhodiola angusta Nakai）叶片部位的内生镰刀霉属微生物（Fusariumsp.HJT‑P‑5）的固体发酵产物为原料，经溶剂萃取和多种色谱方法分离，得到本发明新的呋喃萘醌类化合物；本发明新的呋喃萘醌类物研究化合物在抗肿瘤药开发上具有非常重要的意义。
Description
技术领域
本发明属于医药技术领域，具体涉及从镰刀霉属植物内生微生物代谢产物中提取得到一种新的呋喃萘醌类化合物fusarnaphthoquinones D及其制备方法。
背景技术
目前从微生物代谢产物中分离得到50000种以上的天然产物，其中多种化合物生物活性良好，具有被开发成为新型药物的潜质。随着研究的深入，从传统陆生微生物代谢产物中获得新型先导化合物的概率逐渐降低，速度逐年减缓，故开发特境微生物资源成为当务之急。植物内生微生物由于其生境特殊，能够代谢产生结构特殊，活性良好的化合物，是目前的研究热点之一。
对长白红景天内生微生物Fusarium sp. HJT-P-5的研究表明，其代谢产物含有多种呋喃萘醌类化合物；该类化合物对人肺癌细胞A549和人结肠癌细胞HCT116有明显的抑制活性。
发明内容
本发明的目的是提供一种呋喃萘醌类化合物及其制备方法。
本发明涉及从采集自长白红景天（Rhodiola angusta Nakai）叶片部位的内生镰刀霉属微生物（Fusarium sp. HJT-P-5）的固体发酵产物中分离得到一个新型呋喃萘醌类化合物fusarnaphthoquinones D。药理活性表明这个化合物对人肺癌细胞A549和人结肠癌细胞HCT116有明显的抑制活性。
本发明的技术方案是：一个新的呋喃萘醌类化合物fusarnaphthoquinones D，其分子结构式如下：
该呋喃萘醌类化合物的制备方法是以采集自长白红景天（Rhodiola angustaNakai）叶片部位的内生镰刀霉属微生物（Fusarium sp. HJT-P-5）的固体发酵产物为原料，经溶剂萃取和多种色谱方法分离，得该新的呋喃萘醌类化合物。采用高分辨质谱，核磁共振等谱学技术，确定了该化合物的结构，其制备步骤如下：
（1）将采集自长白红景天（Rhodiola angusta Nakai）叶片部位的内生镰刀霉属微生物（Fusarium sp. HJT-P-5）进行固体发酵；
固体培养基配方：大米，纯净水；
发酵条件：将菌株HJT-P-5接种于真菌4号培养基发酵液的锥形瓶中摇床震荡培养，再将震荡培养的发酵液连同菌丝体接种于装有固体培养基的锥形瓶中静置发酵培养；
（2）代谢产物的提取：使用等体积丙酮对植物内生真菌HJT- P-5固体发酵产物进行超声提取，经8层纱布过滤，将提取液与菌丝体及大米分离，提取液浓缩至干，加水混悬，依次用等体积的乙酸乙酯、正丁醇萃取3次，减压回收溶剂得到乙酸乙酯萃取物和正丁醇萃取物；
（3）乙酸乙酯层用正相硅胶柱色谱分离纯化，采用体积比为氯仿:甲醇= 100:0、100:1、100:2、100:3、100:5、100:10的梯度洗脱，收集洗脱液；
（4）步骤（3）的洗脱液经高效液相色谱分离纯化，采用体积比为乙腈：水=37.5:62.5的溶液洗脱，浓缩后得该化合物。
本发明的有益效果是：本发明的化合物为一种新的呋喃萘醌类化合物，本发明原料为植物内生微生物发酵产物，安全易得，方法简单易操作，不引入有毒物质，成本低廉，可大规模持续开发利用。本发明的化合物在抗肿瘤药物研究开发上具有非常重要的意义。
具体实施方式
以下结合具体实施方式对本发明做进一步说明。
实施例1
呋喃萘醌类化合物fusarnaphthoquinones D的制备
（1）将采集自长白红景天（Rhodiola angusta Nakai）叶片部位的内生镰刀霉属微生物（Fusarium sp. HJT-P-5）进行固体发酵；
固体培养基配方：大米80g，纯净水120ml；
发酵条件：将菌株HJT-P-5接种于4瓶装有200 mL真菌4号培养基发酵液的500 mL锥形瓶中摇床震荡培养2d（培养条件：28℃，120r/min），再将震荡培养2d后的发酵液连同菌丝体按接种量10%的比例接种于40瓶装有固体培养基的500 mL锥形瓶中静置发酵培养40d，（培养条件：28℃）；
（2）代谢产物的提取：使用等体积丙酮对植物内生真菌HJT- P-5固体发酵产物进行超声提取，15min ×3次，经8层纱布过滤，将提取液与菌丝体及大米分离，提取液浓缩至干，加2L水混悬，依次用等体积的乙酸乙酯、正丁醇萃取3次，减压回收溶剂得到乙酸乙酯萃取物（44.66g）和正丁醇萃取物（41.13g）；
（3）乙酸乙酯层用正相硅胶柱色谱分离纯化，采用体积比为氯仿:甲醇= 100:0、100:1、100:2、100:3、100:5、100:10的梯度洗脱，收集洗脱液；
（4）步骤（3）的洗脱液经高效液相色谱分离纯化，采用体积比为乙腈:水=37.5:62.5的溶液洗脱，浓缩后得该化合物。
采用核磁共振（NMR）等波谱技术测定其结构，化合物的波谱数据见下表1。
表1 化合物氢谱(500 MHz)和碳谱(125 MHz)核磁数据（DMSO-d 6）
Claims (1)
1.呋喃萘醌类化合物的制备方法，其特征在于，具有如下结构：
所述制备方法具体步骤为：
(1)将采集自长白红景天(Rhodiola angusta Nakai)叶片部位的内生镰刀霉属微生物(Fusarium sp.HJT-P-5)进行固体发酵；
固体培养基配方：大米，纯净水；
发酵条件：将菌株HJT-P-5接种于真菌4号培养基发酵液的锥形瓶中摇床震荡培养，再将震荡培养的发酵液连同菌丝体接种于装有固体培养基的锥形瓶中静置发酵培养；
(2)代谢产物的提取：使用等体积丙酮对植物内生真菌HJT-P-5固体发酵产物进行超声提取，经8层纱布过滤，将提取液与菌丝体及大米分离，提取液浓缩至干，加水混悬，依次用等体积的乙酸乙酯、正丁醇萃取3次，减压回收溶剂得到乙酸乙酯萃取物和正丁醇萃取物；
(3)乙酸乙酯层用正相硅胶柱色谱分离纯化，采用体积比为氯仿:甲醇＝100:0、100:1、100:2、100:3、100:5、100:10的梯度洗脱，收集洗脱液；
(4)洗脱液经高效液相色谱分离纯化，采用体积比为乙腈:水＝37.5:62.5的溶液洗脱，浓缩后得该化合物。
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