Pseudotrienic Acids A and B, Two Bioactive Metabolites from Pseudomonas sp. MF381-IODS

Abstract

Bioassay-guided fractionation of the liquid culture broth of Pseudomonas sp. MF381-IODS yielded two new antimicrobial substances, identified as (2E,4E,6E)-9-[((2S,3R)-3-hydroxy-4-{[(3E,5E,7RS)-7-hydroxy-4-methylhexadeca-3,5-dienoyl]amino}-2-methylbutanoyl)amino]nona-2,4,6-trienoic acid and the tetradeca equivalent, named pseudotrienic acids A (1) and B (2), respectively. The compounds are prone to lactone formation, and their structures suggest them to be derived from ring opening of a macrolide. Pseudotrienic acids A and B inhibited growth of Staphylococcus aureus (MIC 70 microg/mL) and Pseudomonas syringae pv. syringae (MIC 70 microg/mL). Two known antimicrobial compounds, the polyketide 2,3-deepoxy-2,3-didehydrorhizoxin (3) and the tryptophan-derived pyrrolnitrin (4), were also identified.

Synthesis and Stereochemical Assignment of FR252921, a Promising Immunosuppressant

“…Horner-Wadsworth-Emmons (HWE) homologation of 12 and Staudinger reduction of the azide delivered tert-butyl ester 13 exclusively in the all-E configuration, as judged by 1 H/ 13 C NMR spectroscopy. On the basis of a review of the spectral data for FR252921 [8] and literature precedent for related substructures, [4,9] we opted to prepare the anti 2S,3R stereoisomer and either syn enantiomer of segment C to complete the stereoarray (Scheme 4). To this end, the Evans asymmetric aldol reaction [16] emerged as the most effective of the many enantioselective procedures evaluated.…”

“…[1] Interest in FR252921 from this [2] and other [3,4] laboratories stems in large part from its unique pharmacological profile. In contrast with other immunosuppressants, FR252921 potently inhibits both lipopolysaccharide-(LPS)-stimulated and anti-CD3 mAb-stimulated splenocyte proliferation in vitro without blocking T-cell activation.…”

Paradigm Shifts in Fungal Secondary Metabolite Research: Unusual Fatty Acids Incorporated into Fungal Peptides

“…The in vitro assays showed the enormous potential of pneumocandins, with pneumocandin A showing the best activity at very low concentrations against C. albicans (MIC = 0.06 μg/mL), in the assay with the enzyme 1,3-β-D-glucan (IC 50 = 0.06 μg/mL); and in vivo efficiency against Pneumocystis carinni. Both cyclic lipopeptides contained (10S,12R) (Pohanka et al, 2005). , were produced by Actinomycetesof the genus Chondromyces.…”

Total Synthesis of Pseudotrienic Acid B: A Bioactive Metabolite from Pseudomonas sp. MF 381‐IODS

“…MF 381-IODS. [1] Their structures were established by 1 H NMR (600 MHz) and 13 C NMR (150 MHz) spectroscopy and by ESI mass spectrometry. Each of the pseudotrienic acids A and B was isolated as a 1:1 mixture of epimers at C20, but the absolute configurations at C11 and C12 were well defined as S and R, respectively.…”

“…A previous amide formation between the carboxylic acid 8 and the trienic amine 5 would install the second amide bond. Finally, a crossmetathesis/HWE sequence was envisaged for the initial synthesis of the trienic ester 5 from commercially available methyl sorbate (1).…”