三种活性倍半萜类化合物的生物转化研究
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摘要
本论文首次报道了利用蛹虫草菌作为生物转化体系对天然产物进行结构修饰。通过系统的研究，确定了蛹虫草菌液体培养条件：培养基的组成为：培养基的成分为蔗糖(6.0％)，蛋白胨(0.4％)，硫酸镁(0.05％)，氯化钙(0.01％)，磷酸二氢钾(0.1％)；培养条件为接种量(10％)、发酵温度(24℃)、发酵起始PH(6.0)、转速(150rmp)和光照(弱光)。并对培养液的化学成分进行了研究，分离出32个化合物，鉴定了29个化合物分别为：β-谷甾醇(C-1)；2-乙基酮-3-羟基-4H吡喃酮(C-2)；7，8-二甲基-异咯嗪(C-3)；6-异丁基-吡咯并[1，2a]六氢吡嗪-1，4-二酮(C-4)；6-苄基-吡咯并[1，2a]六氢吡嗪-1，4-二酮(C-5)；6-异丙基-吡咯并[1，2a]六氢吡嗪-1，4-二酮(C-6)；3，7，8-三甲基-异咯嗪(C-7)；1-甲酰基-苯并咪唑(C-8)；3-乙基-4-羟基-6-甲基-2H-吡喃-2-酮(C-9)；胡萝卜苷(C-10)；6-甲基-吡咯并[1，2a]六氢吡嗪-1，4-二酮(C-11)；1-甲基-6-异丁基-2，5-哌嗪二酮(C-12)；1-异丙基-6-异丁基-2，5-哌嗪二酮(C-13)；虫草酸(C-14)；琥珀酸(C-15)；尿嘧啶(C-16)；2-甲基-3-羟基吡啶(C-17)；胸腺嘧啶(C-18)；1-羟甲基-6-异丁基-2，5-哌嗪二酮(C-19)；虫草素(C-20)；腺苷(C-21)；3，6-二(对羟基苄基)-2，5-哌嗪二酮(C-22)；2-吲哚乙基丁二酰胺(C-23)；1-(5-羟甲基)-呋喃-3-羧基-β-咔啉(C-24)；3-乙酰胺基-6-异丁基-2，5-哌嗪二酮(C-25)；3，6-二(3-甲基吲哚)-2，5-哌嗪二酮(C-26)；鸟苷(C-27)；5-异丁基-3，6-氧代-2-哌嗪丙酸(C-28)和麦角甾-7，22-二烯-3β，5，6-三醇(C-29)。其中3-乙酰胺基-6-异丁基-2，5-哌嗪二酮(C-25)为未见文献报道的新化合物。化合物C-8、C-22和C-23为新天然产物。
利用建立起来的蛹虫草菌及其它多种生物转化体系对去氢木香内酯，木香烯内酯和莪二酮进行了生物转化研究。
从38种微生物中筛选出，蛹虫草菌和多型孢毛霉对去氢木香内酯进行了生物转化研究。共分离得到9个化合物，分别为：去氢木香内酯(1)；11α，13-二氢去氢木香内酯(2)；
It was firstly reported that Cordyceps militaris could be used to transform the nature products. The fermentation medium of C. militaris as a biotransformation system was optimized by systemic analysis of the flask fermentation included sugar (6%), yeast extract (0.4%), MgSO_4 (0.05%); CaCl_2(0.01%) and KH-2PO_4(0.1%). The optimum fermentation conditions were 10% of inoculated volume in fermentation condition of fermenting temperature 24 °C, the initial PH value (6.0) and small light needed. At the same time, we studied the chemical constituents in the liquid culture of Cordyceps militaris by various chromatographic methods. 32 compounds were obtained from the liquid culture and the structures of 29 compounds were identified as P-sitosterol (C-l); 2-ethyl-3-hydroxy, 4H-pyran-4-one(C-2); 7, 8-dimethyl-isoalloxazine (C-3); 6-isobutyl-pyrorolo [1,2a] hexahydropyrazine-1, 4-dione (C-4); 6-benzyl-pyrrolo [1,2a] hexahydropyrazine-1, 4- dione (C-5); 6-isopropyl-pyrrolo [1,2a] hexahydropyrazine-1, 4-dione (C-6); 3, 7, 8-trimethyl -isoalloxazine (C-7); 1-formyl-benzpyrazole (C-8); 2H-pyran-2-one, 3-ethyl-4-hydroxy-6-methyl (C-9) ; daucosterol (C-10) ; 6-methyl-pyrorolo [1, 2a] hexahydropyrazine-1, 4-dione (C-11); l-methyl-6-isobutyl-2, 5-piperazine-dione (C-12); l-isopropyl-6-isobutyl-2, 5-piperazine-dione (C-13); D-mannitol (C-14); succinic acid (C-15); uracil (C-16); 2-methyl- 3-hydroxy- pyrolidine (C-17); thymine (C-18); l-hydroxymethyl-6-isobutyl-2, 5-piperazine-dione (C-19); cordycepin (C-20); adenosine (C-21); 3, 6-di-(p-hydroxybenzyl)- 2, 5-piperazine-dione (C-22); succinamide, N, N-bis- [2-(3-indol) -ethyl] (C-23); flazin (C-24); 3- acetamino- 6-isobutyl -2, 5-piperazine-dione (C-25); 3, 6- bis-(3-methyl-indole)-2, 5- piperazine -dione (C-26); guanosin (C-27); 5-isobutyl -3, 6-dioxo-2- piperazinepanoic acid (C-28); ergosta-7, 22-diene-3β, 5, 6-triol (C-29). Among them, 3-acetamino - 6-isobutyl-2, 5-piperazine-dione (C-25) is a new compound. The compounds C-8,
利用建立起来的蛹虫草菌及其它多种生物转化体系对去氢木香内酯，木香烯内酯和莪二酮进行了生物转化研究。
从38种微生物中筛选出，蛹虫草菌和多型孢毛霉对去氢木香内酯进行了生物转化研究。共分离得到9个化合物，分别为：去氢木香内酯(1)；11α，13-二氢去氢木香内酯(2)；
It was firstly reported that Cordyceps militaris could be used to transform the nature products. The fermentation medium of C. militaris as a biotransformation system was optimized by systemic analysis of the flask fermentation included sugar (6%), yeast extract (0.4%), MgSO_4 (0.05%); CaCl_2(0.01%) and KH-2PO_4(0.1%). The optimum fermentation conditions were 10% of inoculated volume in fermentation condition of fermenting temperature 24 °C, the initial PH value (6.0) and small light needed. At the same time, we studied the chemical constituents in the liquid culture of Cordyceps militaris by various chromatographic methods. 32 compounds were obtained from the liquid culture and the structures of 29 compounds were identified as P-sitosterol (C-l); 2-ethyl-3-hydroxy, 4H-pyran-4-one(C-2); 7, 8-dimethyl-isoalloxazine (C-3); 6-isobutyl-pyrorolo [1,2a] hexahydropyrazine-1, 4-dione (C-4); 6-benzyl-pyrrolo [1,2a] hexahydropyrazine-1, 4- dione (C-5); 6-isopropyl-pyrrolo [1,2a] hexahydropyrazine-1, 4-dione (C-6); 3, 7, 8-trimethyl -isoalloxazine (C-7); 1-formyl-benzpyrazole (C-8); 2H-pyran-2-one, 3-ethyl-4-hydroxy-6-methyl (C-9) ; daucosterol (C-10) ; 6-methyl-pyrorolo [1, 2a] hexahydropyrazine-1, 4-dione (C-11); l-methyl-6-isobutyl-2, 5-piperazine-dione (C-12); l-isopropyl-6-isobutyl-2, 5-piperazine-dione (C-13); D-mannitol (C-14); succinic acid (C-15); uracil (C-16); 2-methyl- 3-hydroxy- pyrolidine (C-17); thymine (C-18); l-hydroxymethyl-6-isobutyl-2, 5-piperazine-dione (C-19); cordycepin (C-20); adenosine (C-21); 3, 6-di-(p-hydroxybenzyl)- 2, 5-piperazine-dione (C-22); succinamide, N, N-bis- [2-(3-indol) -ethyl] (C-23); flazin (C-24); 3- acetamino- 6-isobutyl -2, 5-piperazine-dione (C-25); 3, 6- bis-(3-methyl-indole)-2, 5- piperazine -dione (C-26); guanosin (C-27); 5-isobutyl -3, 6-dioxo-2- piperazinepanoic acid (C-28); ergosta-7, 22-diene-3β, 5, 6-triol (C-29). Among them, 3-acetamino - 6-isobutyl-2, 5-piperazine-dione (C-25) is a new compound. The compounds C-8,
引文
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