α-Pyrones with Diverse Hydroxy Substitutions from Three Marine-Derived Nocardiopsis Strains

Abstract

Eight new α-pyrones 1-8 and three known α-pyrones 9-11 were isolated from three marine-derived Nocardiopsis strains SCSIO 10419, SCSIO 04583, and SCSIO KS107. The structures of compounds 1-8 were elucidated by comprehensive spectral analyses. The absolute configurations of 4-deoxyphomapyrone C (1), 4-deoxy-11-hydroxyphomapyrone C (3), 4-deoxy-7R-hydroxyphomapyrone C (5), and phomapyrone C (11) were determined by TDDFT-ECD calculations for the solution conformers, which revealed that the conformation of the side chain was decisive for the sign of the characteristic high-wavelength ECD transition. (-)-4-Deoxy-8-hydroxyphomapyrone C (4) was isolated from SCSIO 10419 and was deduced as a diastereomeric mixture containing (8S)- and (8R)-4-deoxy-8-hydroxyphomapyrone C in a ratio of 2.6:1 (8R:8S), by chiral-phase HPLC analysis and Mosher's ester analysis. Interestingly, 7-hydroxymucidone (9) was isolated from both SCSIO 04583 and SCSIO KS107, as an enantiomeric mixture containing (7S)-hydroxymucidone (major in 9 from SCSIO 04583) and (7R)-hydroxymucidone (major in 9 from SCSIO KS107). α-Pyrones 3-5 were identified as three isomers of phomapyrone C (11) with diverse hydroxy substitutions. α-Pyrones 10-hydroxymucidone (6), 4-hydroxymucidone (8), and 9, differed in the position of the hydroxy group. Several α-pyrones exhibited moderate growth inhibitory activity against Micrococcus luteus and Bacillus subtilis.

Synthesis and Absolute Configuration of Natural 2‐Pyrones

“…Synthetic routes to nectriapyrone, gibepyrone A, racemic gulypyrone A, (+)-germicidin C, (ent)-desoxygermicidin C and (ent)-prolipyrone A via a modular approach are presented, [a] 3144 allowing the assignment of the absolute configurations of the latter three chiral compounds. [12] The optical rotation of synthetic (+)-5 ([α] D 22.0 = +8.9, MeOH, c 0.36) showed the opposite sign as the natural product ([α] D 25.0 = -40, MeOH, c 0.37), [12] resulting in the absolute configuration of (R)-(-)-5 for the material from Nocardiopsis, again confirming the computational assignment. Scheme 3.…”

“…As described above for the synthesis of 3, tosylation of (+)-4 to 19 and subsequent reduction with Zn and HCl gave access to (+)-5 in a yield of 24 % over 5 steps and with 19 % ee as determined by HPLC analysis on a chiral stationary phase ( Figure S4). [12] The optical rotation of synthetic (+)-5 ([α] D 22.0 = +8.9, MeOH, c 0.36) showed the opposite sign as the natural product ([α] D 25.0 = -40, MeOH, c 0.37), [12] resulting in the absolute configuration of (R)-(-)-5 for the material from Nocardiopsis, again confirming the computational assignment. [12] The optical rotation of synthetic (+)-5 ([α] D 22.0 = +8.9, MeOH, c 0.36) showed the opposite sign as the natural product ([α] D 25.0 = -40, MeOH, c 0.37), [12] resulting in the absolute configuration of (R)-(-)-5 for the material from Nocardiopsis, again confirming the computational assignment.…”

“…The method failed for the synthesis of (ent)-phomapyrone B that was thus synthesized via a different route, resulting in an assignment of the absolute configuration of natural phomapyrone B. [12] The synthesis of 6 was pursued starting with asymmetric methylation of the Evans oxazolidinone 20, [31] yielding 21 as a single diastereoisomer (Scheme 4). Synthesis of 4 and 5.…”

“…The NMR spectroscopic data corresponded well to those reported for the natural product from Nocardiopsis. [12] The synthesis of 6 was pursued starting with asymmetric methylation of the Evans oxazolidinone 20, [31] yielding 21 as a single diastereoisomer (Scheme 4). [12] The synthesis of 6 was pursued starting with asymmetric methylation of the Evans oxazolidinone 20, [31] yielding 21 as a single diastereoisomer (Scheme 4).…”

Secondary Metabolites from Polar Organisms

“…Fermentation and isolation of this strain provided two new α-pyrones germicidin H ( 35 ), 4-hydroxymucidone ( 36 ), and a known compound 7-hydroxymucidone. Only the known compound showed antibacterial activity against Micrococcus luteus with an MIC value of 16 μg/mL [31]. …”