Butyrolactones from the Fungus Aspergillus terreus BCC 4651

Abstract

NoteAs part of our research program on the utilization of bioresouces in Thailand, we have been screening fungal extracts for in vitro assays inclusive of antimycobacterial and antiplasmodial activities. An extract from Aspergillus terreus BCC 4651 exhibited moderate activity against Mycobacterium tuberculosis H37Ra (minimum inhibitory concentration (MIC) 25 mg/ml) and the 1 H-NMR spectrum of the extract showed a unique profile, therefore, we selected the strain for large scale fermentation and chemical investigation. This study led to the isolation of two new butenolides, butyrolactones VI (1) and VII (2), together with the known compounds, butylolactone I (3), 1) butyrolactone II (4), 2) butyrolactone IV (5),3) butyrolactone V (6), 4) and aspernolide B (7). 5) A known diketopiperazine, bisdethiodi(methylthio)-acetylaranotin (8), [6][7][8] was also isolated as an antimycobacterial constituent of the culture extract. We report herein the structure elucidation of the new compounds and biological activities of isolated compounds. Results and DiscussionInitial study of the cultures grown in a common liquid medium, Czapek-Dox broth, under shaking resulted in the isolation of the known compounds 3-5, 7, and 8. Further studies revealed that butyrolactone derivatives were efficiently produced when the fungus BCC 4651 was fermented in yeast extract sucrose medium (YES; a sucrose-rich liquid medium) under static conditions. The culture provided with two new compounds 1 and 2 along with 3, 5, 6 and terrein, which is one of the commonly occurring Aspergillus toxins. 9)These compounds were isolated by column chromatography (Sephadex LH-20, silica gel, and reversed-phase HPLC), wherein fractions were analyzed by TLC and 1 H-NMR. Compounds 3-5, and 7 were identified on the basis of the MS and NMR data as butyrolactone I, 1,3) butyrolactone II, 12) Methylation of 6 (MeI, K 2 CO 3 , N,N-dimethylformamide (DMF)) gave the dimethylated derivative 9, which was subsequently converted to the (S)-and (R)-a-methoxy-a-(trifluoromethyl)phenylacetic acid (MTPA) ester derivatives 10a and 10b, respectively. The Dd-values (d S -d R ) of the Mosher esters unambiguously indicated the 8ЉS-configuration (Fig. 1).Butyrolactone VI (1) was isolated as a colorless solid. The molecular formula was determined to be C 24 H 26 O 9 by high resolution-electrospray ionization-mass spectra (HR-ESI-MS). The IR spectrum showed broad and intense absorption bands at n max 3442 (broad) and 1739 cm Ϫ1. The 1 H-and 13 C-NMR spectra were similar to those of other butyrolactone Butyrolactones from the Fungus Aspergillus terreus BCC 4651Rachada HARITAKUN, Pranee RACHTAWEE, Rungtiwa CHANTHAKET, Nattawut BOONYUEN, and Masahiko ISAKA* National Center for Genetic Engineering and Biotechnology; 113 Thailand Science Park, Phaholyothin Road, Klong Luang, Pathumthani 12120, Thailand. Received July 16, 2010; accepted August 3, 2010; published online August 6, 2010 Two new butenolides, butyrolactones VI (1) and VII (2), were isolated together with six known compounds, but...

Four butyrolactones and diverse bioactive secondary metabolites from terrestrial Aspergillus flavipes MM2: isolation and structure determination

“…In accordance, three structural formulas were proposed according to search in AntiBase: butyrolactone-V ( 6 ) [44,45], 4-hydroxy-2-[2-(1-hydroxy-1-methyl-ethyl)-2,3-dihydro-benzofuran-5-ylmethyl]-3-(4-hydroxy-phenyl)-5-oxo-2,5-dihydro-furan-2-carboxylic acid methyl ester ( 8 ) [21] and butyrolactone-III ( 9 ) [19]. …”

Fast identification of the antibacterial in Aspergillus species

“…The effects of butyrolactone I on the prevention of germinal vesicle breakdown, changes of microtubular structures, and development of porcine and bovine oocytes was studied (11,12), but the inhibition effect is temporary and reversible (13). A large number of derivative of butyrolactone I (butyrolactone II-VII and its sulphuric acid derivatives) (9,(14)(15)(16)) also showed various biological activity, which highlights the value of these compounds. Isobutyrolactone II had evident antiviral activity towards HSV-1 with IC 50 values of 21.8 ± 0.8 μg/ml, and butyrolactone V had potent antifouling activity with EC 50 values of 22.1 ± 0.8 μg/ml towards barnacle Balanus amphitrite larvae (17).…”

Bioactive secondary metabolites from endophytes and associated marine derived fungi

“…Butyrolactones were weakly active or inactive against M. tuberculosis, whereas compound 106 exhibited significant growth inhibition with a MIC value of 2.92μM. On the other hand, butyrolactone V (105) showed anti-malarial activity with an IC 50 of 17.95μM (Haritakun et al 2010).…”