Terprenins, Novel Immunosuppressants Produced by Aspergillus candidus.

Kamigauchi, Toshiyuki; Sakazaki, Ryuzi; Nagashima, K.; Kawamura, Yoshimi; Yasuda, Yukio; Matsushima, Keisuke; Tani, Hiroyoshi; Takahashi, Yasuo; Ishii, Kikuo; Suzuki, Ryuji; Koizumi, Kenzo; Nakai, Hiroshi; Ikenishi, Yuji; Terui, Yoshihiro

doi:10.7164/antibiotics.51.445

Cited by 57 publications

(37 citation statements)

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“…4 was identified with 4Љ-deoxyterprenin [4], which has been isolated from the culture of a fungus A. candidus by Kamigauchi et TOF-MS analysis. The 1 H-and 13 C-NMR spectra of 3 were almost superimposable to those of 4 (Tables 1 and 2 [4] reported that terprenins including 4 exhibited immunosuppressive activity. Further biological study for these terphenyllins and terprenins are under way.…”

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Prenylterphenyllin and Its Dehydroxyl Analogs, New Cytotoxic Substances from a Marine-derived Fungus Aspergillus candidus IF10

et al. 2007

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Three novel cytotoxic substances named prenylterphenyllin (1), 4Љ-deoxyprenylterphenyllin (2), and 4Љ-deoxyisoterprenin (3) were isolated from a cultured marine-derived fungus of Aspergillus candidus IF10 together with 4Љ-deoxyterprenin (4). Their chemical structures were elucidated on the basis of 2D NMR analysis. These compounds 1ϳ4 showed cytotoxic activity against human epidermoid carcinoma KB cells (KB3-1) with IC 50 of 8.5, 3.0, 2.5, and 4.5 mg/ml, respectively. Keywords prenylterphenyllin, cytotoxic, marine-derived fungus, Aspergillus candidusIn recent years, marine microorganisms have been paid much attention as a significant source for new drug leads [1,2]. During course of our search for anticancer agent from marine-derived microbe, three novel cytotoxic substances named prenylterphenyllin (1), 4Љ-deoxyprenylterphenyllin (2), and 4Љ-deoxyisoterprenin (3) were isolated from a cultured marine-derived fungus of Aspergillus candidus IF10 together with 4Љ-deoxyterprenin (4) (Fig. 1). In this paper, the fermentation, isolation, and structure elucidation of these compounds are presented.The fungal strain IF10 was isolated from the marine sediment collected from a depth of 50 m off Gokasyo Gulf, Mie Prefecture, Japan, and identified as The slant culture of the strain A. candidus IF10 was inoculated into a 500-ml Erlenmeyer flask containing 200 ml of MG medium [consisting of 2.0% malt extract (Difco, NJ, USA), 2.0% glucose, 0.1% bact peptone (Difco, NJ, USA) in artificial seawater (Yashima Pure Chemicals, Osaka, Japan)] at 30°C for 3 days. Then, 40 ml aliquots of the culture were transferred into 5-liter Erlenmeyer flasks containing 1.0 liter of MG medium and cultured under static conditions at 30°C for 2 weeks. A typical time course of the fermentation is shown in Fig. 3. 1 was detected in the culture broth at day 10 after inoculation, and its concentration reached level of 4.5 mg/liter at day 14. The 2 weeks old culture was extracted with 2-butanone, and the 2-butanone-soluble portion was further partitioned into an n-hexane -90% aq MeOH mixture to furnish a MeOH extract (3.8 g). The MeOH extract (2.1 g) was fractionated by SiO 2 gel column chromatography (n-hexane -EtOAc) to give eight fractions (AϳH) on the guidance of bioassay. Fraction C (73 mg) was then subjected to SiO 2 gel column chromatography (n-hexane -CHCl 3 -EtOAcϭ4 : 1 : 1) to afford 1 (14 mg). Fraction A (50 mg) was separated by SiO 2 gel column chromatography (n-hexane -CHCl 3 -EtOAcϭ10 : 10 : 1) to give four fractions (A-1 to A-4). Fraction A-4 (14 mg) was purified by HPLC (Cosmosil 5SL-II, n-hexane -CHCl 3 -EtOAcϭ4 : 4 : 1) to furnish 2 (2.5 mg). Then, fraction A-3 (20 mg) was separated by HPLC (Cosmosil 5SL-II, n-hexane -CHCl 3 -EtOAcϭ 5 : 5 : 1) to obtain an active fraction A-3-1 (8.0 mg), which was further purified by reversed phase HPLC (Cosmosil 5C 18 -MS-II, CH 3 CN -H 2 Oϭ55 : 45) to afford 3 (1.0 mg) and 4 (4.5 mg).The COSY, HMQC, and HMBC spectra of 1 clarified the presence of three phenyl rings and an isopentenyl moiety a...

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Prenylterphenyllin and Its Dehydroxyl Analogs, New Cytotoxic Substances from a Marine-derived Fungus Aspergillus candidus IF10

et al. 2007

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“…存在于自然界中的三联苯以对位结构为主, 主要存在于蘑菇等真菌类生物中, 间位结构的较少, 而邻位结构的目前还没有被发现 [1] . 含有三联苯结构的化合物常常在免疫抑制活性 [2] 、抗氧化 [3] 、神经保护活性 [4] 、细胞毒活性 [5] 以及抗血栓和抗凝血活性 [6] 等方面具有良好的生物活性. 除此之外, 该类化合物在液晶性和电致发光性方面也表现良好 [7] , 在液晶材料方面有着广泛应用.…”

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Advances in the Synthetic Methods of Terphenyls

Shi¹,

Yu²,

Cui³

2015

Chin. J. Org. Chem.

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Terphenyl derivatives possess various biological activities, such as immunosuppressants, antioxidants, neuroprotective activity, cytotoxic activity, and antithrombotic activity, and they are also widely used in liquid crystal materials. Significant effort has been devoted to the synthesis of such compounds. Classified into coupling reaction, cycloaddition, dehydrogenation and other methods, this review provides a summary of recently developed methods for the preparation of terphenyls.

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“…Treatment of 16 with iodine in the presence of tertbutylamine led to regioselective iodination and the desired iodide 17 in 92 % yield. [12] Although the iodine atom in 17 is located at a more sterically hindered position than the bromine atom, boronic acid 18, conveniently prepared from 13, reacted preferentially at the iodine-substituted position with [Pd 2 (dba) 3 4 ] were added to the reaction mixture, and the expected terphenyl compound 19 was obtained in 70 % yield. Hydrolysis of the protected hemiacetal in 19 with p-toluenesulfonic acid in aqueous acetone followed by a Wittig reaction of 20 with excess isopropyltriphenylphosphonium iodide afforded terprenin (1) in 87 % yield.…”

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“…The structure of terprenin was established on the basis of spectral data and an X-ray crystallographic analysis. [4] Terprenin exhibits a remarkable suppressive effect on the in vitro IgE production of human lymphocytes stimulated with anti-CD40 and IL-4 (IC 50 value of 0.18 nm). In contrast, FK506 shows little or no inhibition even at the high concentration of 1000 nm.…”

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