New bioactive chlorinated cyclopentene derivatives from the marine-derived Fungus Phoma sp

The new halogenated metabolites cryptophomic acid (1), cryptodiol (2), and cryptotriol (3) and the known dihydro-isocoumarin derivative 4, were isolated from the marine-derived fungus Phoma sp.135. The structural elucidation of these compounds was achieved by extensive analysis of spectroscopic data including 1D- and 2D-NMR, HRMS, optical rotation, UV, and IR. The absolute configuration of cryptophomic acid (1) was determined by using circular dichroism and TD-DFT ECD calculations of the solution conformers. The relative configurations of cryptodiol (2) and cryptotriol (3) were elucidated by a detailed analysis of the spectroscopic data and quantum mechanical calculation of NMR chemical shifts, based also on the newly reported + approach. The dihydro-isocoumarin derivative 4 was also produced by the same fungus and its structure was established as (R)-8-hydroxy-6-methoxy-3-methy-3,4-dihydro-isocoumarin (4), often referred to 6-methoxymellein and its chemical structure and absolute configuration were further confirmed through X-ray diffraction analysis. We report here the new compounds 1-3 and the crystallographic data of compound 4 for the first time. Additionally, we report significant antimicrobial activity of compounds 1-3 against Escherichia coli, Bacillus subtilis, Mycobacterium phlei, and Staphylococcus aureus and they showed no lethality against brine shrimp. [GRAPHICS] .