Niduenes A-F,six functionalized sesterterpenoids with a pentacyclic 5/5/5/5/6 skeleton from endophytic fungus Aspergillus nidulans

Niduenes A-F(1-6),six novel sesterterpenoids with unprecedented 5/5/5/5/6 pentacyclic ring skeleton were isolated from endophytic fungus Aspergillus nidulans.Compounds 1 and 2 represent the first examples of aromatic pentacyclic sesterterpenoids.Their structures and configurations were elucidated by spectroscopic data and single-crystal X-ray diffraction analyses.Compound 4 demonstrated potent resensitization of SW620/AD300 cells to paclitaxel(PTX).Rhodamine 123 accumulation assay and docking analysis further support that 4 inhibitory the efflux function of P-glycoprotein(P-gp).

Genomics-driven derivatization of the bioactive fungal sesterterpenoid variecolin:Creation of an unnatural analogue with improved anticancer properties

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin(1)and variecolactone(2)was identified in Aspergillus aculeatus ATCC 16872.Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB.Intriguingly,the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues(5-7).Analysis of the compounds’anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities,5 was associated with significantly reduced toxic side effects in cancer-bearing mice,indicating its potentially broader therapeutic window.Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

Glasesterterpenoids A-C:three sesterterpenoids with 7-cyclohexyl-decahydronaphthalene carbon skeleton isolated from the root of Lindera glauca

Three novel sesterterpenoids glasesterterpenoids A-C(1-3),featuring an unprecedented 7-cyclohexyldecahydronaphthalene carbon skeleton,were isolated from the root of Lindera glauca(L.glauca).Their structures were elucidated by quantum chemical calculations and spectroscopic methods.The biogenetic pathway for 1-3 is proposed.In the bioassay,glasesterterpenoid C exhibited DNA topoisomerase 1(Top1)inhibitory activity compared with the positive control,camptothecin.These findings represent the first examples of sesterterpenoids with a 7-cyclohexyldecahydronaphthalene carbon skeleton from the root of L.glauca.

Characterization of two chimeric sesterterpene synthases from a fungal symbiont isolated from a sesterterpenoid-producing Lamiaceae plant Leucosceptrum canum

Two chimeric sesterterpene synthases(Aa TPS1 and Aa TPS2)were functionally characterized from Alternaria alternata MB-30 isolated from the leaves of a sesterterpenoid-producing Lamiaceae plant Leucosceptrum canum.Aa TPS1 generated a 5/8/6/5 tetracyclic sesteraltererol(1)and its absolute stereochemistry was determined by X-ray crystallographic analysis of its derivative 10,11-epoxysesteraltererol(2),which enabled revision of the absolute configuration of C7 of sesterfisherol produced by Nf SS and PTTS014 characterized previously and its derivative 10,11-epoxysesterfisherol.Aa TPS2 produced a 5/15 bicyclic preterpestacin I(3).Site-directed mutagenesis suggested that F192 in Aa TPS1 was likely involved in controlling of the hydroxylation of C12,and eight amino acids were important for the enzyme activity of Aa TPS1 and Aa TPS2.The engineered Escherichia coli and Saccharomyces cerevisiae strains were constructed for the productions of compounds 1 and 3,and the highest titer of compound 1 reached 62.3 mg/L in shake-flask culture.Both compounds 1 and 2 showed anti-adipogenic activity.

Natural Sesquiterpenoids, Diterpenoids, Sesterterpenoids, and Triterpenoids with Intriguing Structures from 2017 to 2022

This review covers the isolation,structural determination,plausible biosynthetic pathways,and biological activities of 166 natural terpenoids including 57 sesquiterpenoids,65 diterpenoids,15 sesterterpenoids,and 29 triterpenoids from January 2017 to December2022.

南海海绵Dactylospongia elegans的二倍半萜类化学成分及抗炎活性研究

利用溶剂分步萃取、正相硅胶柱层析、反相ODS柱层析和高效液相等多种色谱技术对中国南海海绵Dactylospongia elegans的化学成分进行分离纯化,通过波谱学手段并结合文献比对鉴定化合物的结构。从二氯甲烷萃取部位分离鉴定了8个化合物:dactylospene F(1)、scalarin(2)、honulactone A(3)、honulactone B(4)、honulactone E(5)、honulactone F(6)、honulactone I(7)、honulactone J(8),其中化合物1为新化合物,化合物2~8为首次从该海绵中分离得到。对8个化合物的抗炎活性进行了评价,结果显示化合物1、3、4在10μmol/L时对脂多糖诱导的一氧化氮生成有较好的抑制作用,抑制率分别为65.5%、48.5%、46.0%,且对小鼠巨噬细胞RAW 264.7无细胞毒性。

中国南海海绵Hyrtios erectus中二倍半萜类化学成分

目的 :为寻找具有独特生物活性的海洋次生代谢产物 ,对中国南海海绵Hyrtioserectus的化学成分进行了系统分离。方法 :采用多种层析手段进行分离纯化 ,应用多种波谱分析技术 ,并结合文献对照 ,对所分离到的化合物进行了结构鉴定。结果 :共分离得到 8个五环二倍半萜化合物 ,其结构分别为furoscalarol (Ⅰ ) ,12 O deacetylfuroscalarol (Ⅱ ) ,16 deacetyl 12 epi scalarafuranacetate (Ⅲ ) ,isoscalarafuran A (Ⅳ ) ,scalarin (Ⅴ ) ,12 O deacetyl 19 deoxyscalarin (Ⅵ ) ,12 epi deoxoscalarin (Ⅶ ) ,2 1 hydroxydeoxoscalarin (Ⅷ )。结论 :本文系首次对中国南海海绵Hyrtioserectus的化学成分研究进行报道 ,化合物Ⅳ ,Ⅶ 。

具有生物活性的scalarane型二倍半萜类海洋天然产物的研究进展

大多数scalarane型二倍半萜类海洋天然产物具有较好的抗肿瘤和抗结核病的药理活性。因此,越来越多的研究人员致力于此类化合物的合成研究,并取得了一定的进展。本文对此类化合物的研究背景、生物药理活性以及最新的合成进展进行介绍和综述,并对其研究前景进行展望。

杯叶海绵的化学成分研究

目的对采自西沙永乐群岛海域的杯叶海绵Phyllospongia foliascens进行系统的化学成分研究。方法综合运用硅胶柱色谱、十八烷基硅烷键合硅胶填料(ODS)柱色谱、Sephadex LH-20凝胶柱色谱、半制备高效液相色谱等技术进行分离纯化得到单体化合物。采用高分辨电喷雾电离质谱、核磁共振波谱、圆二色谱结合文献比对等方法鉴定其结构。对分离得到的化合物进行细胞毒活性评价。结果从杯叶海绵的石油醚萃取物中分离鉴定了7个单体化合物,包括1个新scalarane型二倍半萜:杯叶海绵萜U(1);以及已知的4个scalarane型二倍半萜:phyllofolactone Q(2)、phyllofolactone R(3)、carteriofenone I(4)、carteriofenone G(5);2个甾醇:5α,8α-epidioxycholest-6-en-3β-ol(6)和(22E)-5α,8α-epidioxyergosta-6,22-dien-3β-ol(7)。化合物1对Daudi细胞和Raji细胞增殖有抑制作用,半数抑制浓度(half maximal inhibitory concentration,IC50)值分别为2.23、15.24μmol/L。结论化合物1为新化合物,具有细胞毒活性,化合物4~6为杯叶海绵中首次分离得到的化合物。

Leucosceptroid B from glandular trichomes of Leucosceptrum canum reduces fat accumulation in Caenorhabditis elegans through suppressing unsaturated fatty acid biosynthesis

Obesity that is highly associated with numerous metabolic diseases has become a global health issue nowdays.Plant sesterterpenoids are an important group of natural products with great potential;thus,their bioactivities deserve extensive exploration.RNA-seq analysis indicated that leucosceptroid B,a sesterterpenoid previously discovered from the glandular trichomes of Leucosceptrum canum,significantly regulated the expression of 10 genes involved in lipid metabolism in Caenorhabditis elegans.Furthermore,leucosceptroid B was found to reduce fat storage,and downregulate the expression of two stearoyl-CoA desaturase(SCD)genes fat-6 and fat-7,and a fatty acid elongase gene elo-2 in wild-type C.elegans.In addition,leucosceptroid B significantly decreased fat accumulation in both fat-6 and fat-7 mutant worms but did not affect the fat storage of fat-6;fat-7 double mutant.These findings indicated that leucosceptroid B reduced fat storage depending on the downregulated expression of fat-6,fat-7 and elo-2 and thereby inhibiting the biosynthesis of the corresponding unsaturated fatty acid.These findings provide new insights into the development and utilization of plant sesterterpenoids as potential antilipemic agents.

二倍半萜类天然产物的生物合成研究进展

二倍半萜是由五个异戊二烯单元构成、生物合成来源于香叶基法尼基焦磷酸酯的一类珍稀萜类天然产物,迄今仅报道了1 300余个,其分布广泛、结构新颖复杂、生物活性显著。近10年来,随着基因组挖掘和异源表达技术的发展,二倍半萜生物合成研究取得了系列重要进展。本文主要概述了二倍半萜生物合成途径的研究,包括香叶基法尼基焦磷酸酯合酶、二倍半萜合酶和氧化酶的生化功能和催化机制,以期为该类天然产物生物合成、生物活性与合成生物学的深入研究提供参考。

中国南海海绵Luf fariella sp.的次生代谢产物研究

目的研究中国南海海绵Luffariellasp.的次生代谢产物及生物活性。方法利用硅胶柱色谱、C18反相柱色谱,半制备HPLC等方法对海绵提取物进行分离纯化,通过核磁共振、质谱、紫外、红外等波谱学技术,并结合文献理化数据,确定化合物的结构。对分离得到的化合物进行了NF-κB抑制活性评价实验。结果分离鉴定了6个含α、β-不饱和γ–内酯环的二倍半萜类化合物,结构确定为Hippolide H(1)、Hippolide F(2)、Hippolide G(3)、Hippolide E(4)、6Z-neomanoalide(5)、6E-neomanoalide(6)。在NF-κB抑制活性评价实验中,化合物1、4、6具有较好的NF-κB抑制活性。结论南海海绵Luffariellasp.可代谢具有NF-κB抑制活性的二倍半萜类化合物。

丝状真菌二倍半萜化合物及其合成酶

相比其他萜类化合物,丝状真菌来源的二倍半萜化合物数量较少,但具有广泛的生理活性和药用价值。已经发现的丝状真菌二倍半萜合成酶均由萜类环化酶和异戊烯基转移酶两个结构域组成,表现出底物的非特异性和环化方式的多样性。本文重点叙述了丝状真菌来源的二倍半萜化合物以及其合成酶的结构与功能特征,并对丝状真菌二倍半萜化合物及其合成酶研究现状作简要概述。