Synoxazolidinones A and B: Novel Bioactive Alkaloids from the Ascidian Synoicum pulmonaria

Abstract

Bioassay-guided fractionation of the sub-Arctic ascidian Synoicum pulmonaria collected off the Norwegian coast led to the isolation of a novel family of brominated guanidinium oxazolidinones named synoxazolidinones A and B (1 and 2). The backbone of the compounds contains a 4-oxazolidinone ring rarely seen in natural products. The structure of the compounds was determined by spectroscopic methods. The synoxazolidinones exhibited antibacterial and antifungal activities.

Secondary Metabolites from Polar Organisms

“…From the sub-Arctic ascidian Synoicum pulmonaria collected off the Norwegian coast, three new brominated guanidinium oxazolidinones were isolated, named synoxazolidinones A–C ( 215 – 217 ) (Figure 20) [141,142,143]. The backbone of the compounds contains a 4-oxazolidinone ring rarely seen in natural products.…”

“…The backbone of the compounds contains a 4-oxazolidinone ring rarely seen in natural products. Synoxazolidinones A ( 215 ) and B ( 216 ) exhibited antibacterial and antifungal activities, and 215 displayed higher activity than 216 because of the chlorine atom in its structure [141]. Synoxazolidinone C could inhibit the growth of Gram-positive bacteria Staphylococcus aureus and methicillin-resistant S. aureus at a concentration of 10 μg/mL [142].…”

Marine Pharmacology in 2009–2011: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action

“…bacterium [45]; two novel α-pyrone macrolides neurymenolides A and B ( 26 , 27 ) isolated from the Fijian red alga Neurymenia fraxinifolia [46]; two polybrominated metabolites ( 28 , 29 ) from a Hawai’ian marine bacterium Pseudoalteromonas sp. found on the surface of a nudibranch [47]; pseudopterosin U ( 30 ) discovered in the Caribbean octocoral Pseudopterogorgia elisabethae [48]; 5-bromo-8-methoxy-1-methyl-β-carboline ( 31 ), an alkaloid isolated from the New Zealand marine bryozoan Pterocella vesiculosa [49]; a new rifamycin antibiotic, salinisporamycin ( 32 ), purified from a culture of the Micronesian marine actinomycete Salinispora arenicora YM23-082 [50]; a novel bioactive alkaloid, synoxazolidinone A ( 33 ), discovered in the sub-Arctic Norwegian ascidian Synoicum pulmonaria [51]. …”

“…Finally, several novel structurally-characterized marine molecules demonstrated MICs or IC 50 s greater than 10 μg/mL or 10 μM, and therefore, because of the reported weaker antifungal activity, have been excluded from Table 1 and Figure 1: the maleimide mixture aqabamycin E ( 6 ) (MIC = 50 μg/mL) [34]; the novel antibacterial alkaloid synoxazolidinone A ( 33 ) (MIC = 12.5 μg/mL) [51], and the new bromotyrosine tyrokeradine B (MIC = 12.5 μg/mL) [100]. …”

5-Benzylidene-4-oxazolidinones potently inhibit biofilm formation in Methicillin-resistant Staphylococcus aureus

“…The marine natural product synoxazolidinone A ( 1 , Figure 1) possesses an unusual 5-benzylidene-4-oxazolidinone core decorated with a brominated aromatic moiety and chlorinated, guanidine-containing sidechain 25 . Recent efforts in our lab to develop new synthetic methods for the synthesis of these unusual heterocycles culminated in the first total synthesis of (±)-synoxazolidinone A ( ±-1 ) 26 .…”