Thielavialides A–E, Nor-Spiro-azaphilones, and a Bis-spiro-azaphilone from Thielavia sp. PA0001, An Endophytic Fungus Isolated from Aeroponically Grown Physalis alkekengi

Abstract

Four new nor-spiro-azaphilones, thielavialides A–D (1– 4), a new bis-spiro-azaphilone, thielavialide E (5), together with pestafolide A (6), were isolated from the endophytic fungal strain, Thielavia sp. PA0001, occurring in the healthy leaf tissue of aeroponically grown Physalis alkekengi. The structures and relative configurations of 1–5 were established on the basis of their MS and NMR data. Possible biosynthetic pathways to thielavialides A–E (1– 5) from pestafolide A (6), some involving a Favorskii-like rearrangement, are proposed.

Recent advances in the chemistry and biology of azaphilones

“…This subgroup of azaphilones is characterized by an austdiol core with nineteen members (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46) (Fig. 3 and Table 1), including fusaraisochromenone (28), 25 7(S)-7-hydroxy-3,7dimethyl-isochromene-6,8-dione (32), 26 nemanecins A-C (34-36), 27 and perangustols A and B (37)(38).…”

“…17 Chemical analysis of the fungus Dothideomycete sp. CRI7 afforded ve austdiol-like azaphilones, dothideomynones B-F (39)(40)(41)(42)(43), while compounds 41-43 were obtained from the fermentation broths under deionized water supplemented with potassium bromide. 33,34 Of particular…”

“…Nemania sp. BCC 30850 27 Perangustols A-B (37)(38) Cladosporium perangustum FS62 28 Dothideomynone C (40) Dothideomycete sp. CRI7 33 Cytotoxic (A549: 46.5 mg mL À1 , HuCCA-1: 48.1 mg mL À1 , MOLT-3: 17.4 mg mL À1 ) Dothideomynones B (39), D-F (41)(42)(43) Dothideomycete sp.…”

“…BS4 37 Antimicrobial (Escherichia coli: 5.0 mg mL À1 ) Coniellin A (57) Coniella fragariae 9 Anti-tumor (MDA-MB-231: 21.5 mM, inhibit NF-kB activation: 4.4 mM) Coniellin B (58) Coniella fragariae 9 Anti-tumor (MDA-MB-231: 19.6 mM) Coniellin C (59) Coniella fragariae 9 Anti-tumor (MDA-MB-231: 21.0 mM) Coniellin D (60) Coniella fragariae 9 Anti-tumor (MDA-MB-231: 18.6 mM, inhibit NF-kB activation: 37.8 mM) Coniellin E (61) Coniella fragariae 9 Anti-tumor (MDA-MB-231: 79.3 mM, inhibit NF-kB activation: 29.4 mM) Coniellin F (62) Coniella fragariae 9 Anti-tumor (inhibit NF-kB activation: 70.7 mM) Coniellin G (63) Coniella fragariae 9 Anti-tumor (MDA-MB-231: 21.6 mM, inhibit NF-kB activation: 11.3 mM) Coniellins H-I (64)(65) Coniella fragariae 35 5 0 ,6 0 -Dihydroxyacetosellin (66) Epicoccum nigrum strain 749 38 Monakaocinol 67Monascus kaoliang 39 Monascuspirolide A (68) Monascus purpureus BCRC 38110 42 Anti-inammatory (inhibit NO production: 17.5 mM) Monascuspirolide B (69) Monascus purpureus BCRC 38110 42 Anti-inammatory (inhibit NO production: 23.5 mM) Thielavialides A-E (70)(71)(72)(73)(74) Thielavia sp. PA0001 40…”

“…Ten compounds belonged to hydrogenated spiro-azaphilones with a veor six-membered ring spiroketal system on the azaphilone skeleton ( Fig. 5 and Table 1), such as thielavialides A-E (70-74), 40 5-O-acetyl-epi-pestafolide A (75), 41 and 5-epi-pestafolide A (76). 41 Herein, monascuspirolides A and B (68-69) bearing with an unique 5 0 ,6 0 -dihydrospiro[isochromane-1,2 0 -pyran]-4 0 (3 0 H)-one pattern, were isolated from Monascus purpureus BCRC 38110.…”