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海洋来源真菌ZJ-M-5中可“天然降解”的多聚内酯类化合物
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摘要
从海洋来源真菌Ascotricha sp.ZJ-M-5在去除Mg~(2+)离子的查氏培养基静置培养物中分离得到3个新的链状聚酮来源的多聚酯类化合物ascotrichesters A-C(1-3)、1个新的大环多聚内酯ascotrichalactone A(4),一个新的聚己酮orthosporinin(5)及其二聚物diorthosporinin(6),以及2个已知的生合成前体(-)-orthosporin(7)和(-)-6-hydroxymellein(8)。通过对化合物4在不同pH值水溶液中稳定性以及ZJ-M-5次生代谢产物随时间变化情况的考察,我们认为大环多聚内酯结构4应该是真菌真正产生的代谢产物,而具有与其相同聚酮片段连接顺序的链状结构(3),及化合物5应该是其"天然降解产物",这与之前学者提出的生合成路径是相反的。此外,我们还测试了上述化合物的体外抗肿瘤活性及化合物3-4的抑菌活性。
Four new polyketide-derived polyesters,including three linear ones ascotrichesters A-C(1-3) and one macrocyclic ascotrichalactone A(4),and the known biosynthetic building blocks(-)-orthosporin(7) and(-)-6-hydroxymellein(8),were isolated from the still culture product of the fiingus Ascotricha sp.ZJ-M-5 in Czapek Dox broth without Mg~(2+),along with a new hexaketide orthosporinin(5) and its visible light-catalyzed[2+2]dimerized derivative diorthosporinin(6).HPLC monitoring of the stability of 4 in H_2O disclosed the fact that macrocyclic lactone4,is the natural precursor which undergoes "natural degradation" to yield the linear polyester 3 and parallel reactions to afford 5.This result demonstrated that the previously proposed biosynthetic pathway for polyesters from linear to cyclic should be reversed.Additionally,the growth inhibitory effects of 1-8 against two human leukemia cancer cell lines and the antibacterial activities of compounds 3 and 4 were assessed.
引文
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    [3]Schlingmann G,Roll DM.Absolute stereochemistry of unusual biopolymers from Ascomycete culture LL-W1278:Examples that derivatives of(S)-6-hydroxymellein are also natural fungal metabolites[J].Chirality,.2005,17:S48-S51.
    [4]Ruanglek V,Chokpaiboon S,Rattanaphan N,et al.Menisporopsin B,a new polyester from the seed fungus Menisporopsis theobromae BCC 4162[J].J Antibiot,2007,60:748-751.
    [5]Schlingmann G,Milne L,Carter GT.Isolation and identification of antifungal polyesters from the marine fungus Hypoxylon oceanicum LL-15G256[J].Tetrahedron,2002,58:6825-6835.

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