β-Resorcylic Acid Lactones from a Paecilomyces Fungus

Abstract

Six new beta-resorcylic acid lactones (1-6), named paecilomycins A-F, and five known compounds, aigilomycin B (7), zeaenol (8), aigialomycin D (9), aigialomycin F (10), and aigialospirol, were isolated from the mycelial solid culture of Paecilomyces sp. SC0924. Their structures were elucidated by extensive NMR analysis, single-crystal X-ray study, and chemical correlations. Compounds 5 and 10 exhibited antiplasmodial activity against Plasmodium falciparum line 3D7 with IC(50) values of 20.0 and 10.9 nM, respectively, and compounds 5-7 showed moderate activity against the P. falciparum line Dd2.

Stereoselective total synthesis of the antiplasmodial resorcylic acid lactone paecilomycin F

“…The geometry of the product was characterized based on the coupling constant value of 14.9 Hz for the olefinic protons. The compound 24 when exposed to 2N HCl for 15 h underwent complete deprotection of MOM and acetonide functionalities furnishing the target molecule paecilomycin F. The spectroscopic data of the synthesized product was in full agreement with the reported data 16,18 of the natural product (See …”

“…Over the years, these molecules have emerged as common targets for total synthesis and have led medicinal chemists to design analog programmes leading to a number of clinical trials. [12][13][14][15] Chen et al have recently isolated six new resorcylic acid lactones, namely paecilomycin A-F [16][17][18] ( Figure 1) along with other known RALs from the mycelial solid culture of Paecilomyces fungus SC0924. Interestingly, when these compounds were subjected to screening for plasmodicidal activity, paecilomycin F was found to display antiplasmodial activity against Plasmodium falciparum line 3D7 with an IC 50 value of 20.0 nM and moderate activity against P. falciparum line Dd2.…”

Convergent and stereoselective synthesis of (−)-zeaenol

“…The residue was purified by column chromatography (petroleum ether-EtOAc, 4:1) to give 19 (2.73 g, 82%) as a colorless oil. 2,128.5,128.0,127.8,109.9,96.2,80.4,78.9,77.9,76.2,73.6,71.6,70.7,56.1,27.4,27.3,21.7;MS (ESI) …”

“…IR (KBr) ν max = 2924, 2854, 1711, 1649, 1548, 1458, 1377, 1315, 1253, 1210, 1116, 1035, 967, 921, 743, 631, 508, 484 cm -1 . 1 H NMR (300 MHz, CDCl 3 ): 11.54 (s, 1H), 7.17 (dd, J = 15.4, 2.0 Hz, 1H), 6.46 (d, J = 2.6 Hz, 1H), 6.40 (d, J = 2.6 Hz, 1H), 5.99 (ddd, J = 15.4, 8.4, 7.0 Hz, 1H), 5.72 (ddd,J = 15.4,10.7,3.1 Hz,1H),5.54 (dd,J = 15.4,8.4,1.2 Hz,1H),1H),4.48 (d,J = 6.7 Hz, 1H), 4.73 (d, J = 6.7 Hz, 1H), 4.63(t, J = 8.0 Hz, 1H), 4.15 (ddd,J = 12.4,5.2,1.8 Hz,1H),3.89 (dd,J = 7.8,2.0 Hz, 1H), 3.82 (s, 3H), 3.44 (s, 3H), 2.57-2.41 (m, 2H), 2.37-2.26 (m, 2H), 1.44 (d, J = 6.4 Hz, 3H), 1.41 (s, 3H), 1.36 (s, 3H). 13 C NMR (75 MHz, CDCl 3 ): 170.…”

“…SC0924. 2 They exhibit various pharmacological activities such as antitumor, 3 antifungal, 4 antifouling 5 and antimalarial. 6 (5Z)-7-Oxozeaenol is a potent inhibitor of the NF-κB pathway and also significantly enhances the chemotherapeutic efficacy.…”