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Lindgomycin, an Unusual Antibiotic Polyketide from a Marine Fungus of the Lindgomycetaceae.

Wu B, Wiese J, Labes A, Kramer A, Schmaljohann R, Imhoff JF - Mar Drugs (2015)

Bottom Line: In the new polyketide, two distinct domains, a bicyclic hydrocarbon and a tetramic acid, are connected by a bridging carbonyl.The combination of 5-benzylpyrrolidine-2,4-dione of compound 1 in its tetramic acid half and 3-methylbut-3-enoic acid pendant in its decalin half allow the assignment of a new carbon skeleton.The new compound 1 and ascosetin showed antibiotic activities with IC50 value of 5.1 (±0.2) µM and 3.2 (±0.4) μM, respectively, against methicillin-resistant Staphylococcus aureus.

View Article: PubMed Central - PubMed

Affiliation: GEOMAR Helmholtz Centre for Ocean Research Kiel, 24105 Kiel, Germany. wubin@zju.edu.cn.

ABSTRACT
An unusual polyketide with a new carbon skeleton, lindgomycin (1), and the recently described ascosetin (2) were extracted from mycelia and culture broth of different Lindgomycetaceae strains, which were isolated from a sponge of the Kiel Fjord in the Baltic Sea (Germany) and from the Antarctic. Their structures were established by spectroscopic means. In the new polyketide, two distinct domains, a bicyclic hydrocarbon and a tetramic acid, are connected by a bridging carbonyl. The tetramic acid substructure of compound 1 was proved to possess a unique 5-benzylpyrrolidine-2,4-dione unit. The combination of 5-benzylpyrrolidine-2,4-dione of compound 1 in its tetramic acid half and 3-methylbut-3-enoic acid pendant in its decalin half allow the assignment of a new carbon skeleton. The new compound 1 and ascosetin showed antibiotic activities with IC50 value of 5.1 (±0.2) µM and 3.2 (±0.4) μM, respectively, against methicillin-resistant Staphylococcus aureus.

No MeSH data available.


Related in: MedlinePlus

Key 1H–1H COSY and HMBC correlations of compound 1.
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marinedrugs-13-04617-f003: Key 1H–1H COSY and HMBC correlations of compound 1.

Mentions: The 18 signals for the hydrocarbon domain comprised four methyls (δC 15.6, 17.3, 22.9, and 22.9), three methylenes (δC 43.7, 37.1, and 29.6), four methines (δC 58.0, 39.9, 41.6, and 34.8), a quaternary carbon (δC 52.2), two sets of double bonds (130.8, 129.5, 159.8, and 121.5), a carboxylic carbon (δC 169.6), and enol carbon (δC 201.4). In the COSY spectrum of 1 (Figure 3), the methine proton at δH 1.88 (m, H-6) was coupled with another methine proton at δH 1.81 (m, H-11), the methylene protons at δH 1.87 (m, H-7α) and 0.90 (m, H-7β), and the olefin proton at 5.41, (br s, H-5). The methine proton at δH 1.54 (m, H-8) exhibited cross peaks with methylene protons of H2-7, H2-9, and methyl protons at δH 0.93 (d, J = 6.5 Hz, Me-17) in the COSY spectrum of 1. The sequence of a six-member ring system of H-6/H2-7/H-8/H2-9/H2-10/H-11 with Me at C-8 was deduced from the above 1H–1H COSY analyses (Figure 3). HMBC analyses complete the formation of the decalin skeleton with a characteristic sec-butyl pedant (Figure 3). HMBC cross peaks of Me-17/C-7 and Me-17/C-9 confirmed the position of methyl group at C-8 of ring A. In the 1H NMR spectrum of 1, two methyl groups displayed two singlet signals, one of which was assigned at quaternary C-2 from the observation of HMBC cross peaks of Me-12/C-1 and Me-12/C-2. The long range correlations from the proton at δH 1.54 (s, Me-18) to the double bond carbon signals at δC 130.8 (s, C-4) and δC 129.5 (d, C-5) positioned the remaining methyl at C-4. The pendant attached at C-3 was obviously different from the known phomasetin. Instead of being a penta-diene, a 3-methylbut-3-enoic acid unit was attached at C-3. The carboxylic carbon at δC 169.6 (s) was attributed to C-15 from the observation of long range correlations from the proton signals at δH 5.63 (s, H-14) to carboxylic C-15. The methyl group in the pendant was assigned at C-13 from analysis of the HMBC cross peaks from Me-16 to olefinic C-13 and C-14. The substructure of the pedant was deduced to be a 3-methylbut-3-enoic acid unit, which was positioned at C-3 from the observation of HMBC correlation from the proton at δH 3.46 (s, H-3) to the carbon at δC 159.8 (s, C-13) and HMBC correlations from the Me proton at δH 1.91 (s, Me-16) and olefinic proton at δH 5.63 (s, H-14) to the carbon signal at δC 58.0 (C-3). The two-dimensional NMR analyses mentioned above permitted the assignment of the bicyclic hydrocarbon unit of 1.


Lindgomycin, an Unusual Antibiotic Polyketide from a Marine Fungus of the Lindgomycetaceae.

Wu B, Wiese J, Labes A, Kramer A, Schmaljohann R, Imhoff JF - Mar Drugs (2015)

Key 1H–1H COSY and HMBC correlations of compound 1.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556996&req=5

marinedrugs-13-04617-f003: Key 1H–1H COSY and HMBC correlations of compound 1.
Mentions: The 18 signals for the hydrocarbon domain comprised four methyls (δC 15.6, 17.3, 22.9, and 22.9), three methylenes (δC 43.7, 37.1, and 29.6), four methines (δC 58.0, 39.9, 41.6, and 34.8), a quaternary carbon (δC 52.2), two sets of double bonds (130.8, 129.5, 159.8, and 121.5), a carboxylic carbon (δC 169.6), and enol carbon (δC 201.4). In the COSY spectrum of 1 (Figure 3), the methine proton at δH 1.88 (m, H-6) was coupled with another methine proton at δH 1.81 (m, H-11), the methylene protons at δH 1.87 (m, H-7α) and 0.90 (m, H-7β), and the olefin proton at 5.41, (br s, H-5). The methine proton at δH 1.54 (m, H-8) exhibited cross peaks with methylene protons of H2-7, H2-9, and methyl protons at δH 0.93 (d, J = 6.5 Hz, Me-17) in the COSY spectrum of 1. The sequence of a six-member ring system of H-6/H2-7/H-8/H2-9/H2-10/H-11 with Me at C-8 was deduced from the above 1H–1H COSY analyses (Figure 3). HMBC analyses complete the formation of the decalin skeleton with a characteristic sec-butyl pedant (Figure 3). HMBC cross peaks of Me-17/C-7 and Me-17/C-9 confirmed the position of methyl group at C-8 of ring A. In the 1H NMR spectrum of 1, two methyl groups displayed two singlet signals, one of which was assigned at quaternary C-2 from the observation of HMBC cross peaks of Me-12/C-1 and Me-12/C-2. The long range correlations from the proton at δH 1.54 (s, Me-18) to the double bond carbon signals at δC 130.8 (s, C-4) and δC 129.5 (d, C-5) positioned the remaining methyl at C-4. The pendant attached at C-3 was obviously different from the known phomasetin. Instead of being a penta-diene, a 3-methylbut-3-enoic acid unit was attached at C-3. The carboxylic carbon at δC 169.6 (s) was attributed to C-15 from the observation of long range correlations from the proton signals at δH 5.63 (s, H-14) to carboxylic C-15. The methyl group in the pendant was assigned at C-13 from analysis of the HMBC cross peaks from Me-16 to olefinic C-13 and C-14. The substructure of the pedant was deduced to be a 3-methylbut-3-enoic acid unit, which was positioned at C-3 from the observation of HMBC correlation from the proton at δH 3.46 (s, H-3) to the carbon at δC 159.8 (s, C-13) and HMBC correlations from the Me proton at δH 1.91 (s, Me-16) and olefinic proton at δH 5.63 (s, H-14) to the carbon signal at δC 58.0 (C-3). The two-dimensional NMR analyses mentioned above permitted the assignment of the bicyclic hydrocarbon unit of 1.

Bottom Line: In the new polyketide, two distinct domains, a bicyclic hydrocarbon and a tetramic acid, are connected by a bridging carbonyl.The combination of 5-benzylpyrrolidine-2,4-dione of compound 1 in its tetramic acid half and 3-methylbut-3-enoic acid pendant in its decalin half allow the assignment of a new carbon skeleton.The new compound 1 and ascosetin showed antibiotic activities with IC50 value of 5.1 (±0.2) µM and 3.2 (±0.4) μM, respectively, against methicillin-resistant Staphylococcus aureus.

View Article: PubMed Central - PubMed

Affiliation: GEOMAR Helmholtz Centre for Ocean Research Kiel, 24105 Kiel, Germany. wubin@zju.edu.cn.

ABSTRACT
An unusual polyketide with a new carbon skeleton, lindgomycin (1), and the recently described ascosetin (2) were extracted from mycelia and culture broth of different Lindgomycetaceae strains, which were isolated from a sponge of the Kiel Fjord in the Baltic Sea (Germany) and from the Antarctic. Their structures were established by spectroscopic means. In the new polyketide, two distinct domains, a bicyclic hydrocarbon and a tetramic acid, are connected by a bridging carbonyl. The tetramic acid substructure of compound 1 was proved to possess a unique 5-benzylpyrrolidine-2,4-dione unit. The combination of 5-benzylpyrrolidine-2,4-dione of compound 1 in its tetramic acid half and 3-methylbut-3-enoic acid pendant in its decalin half allow the assignment of a new carbon skeleton. The new compound 1 and ascosetin showed antibiotic activities with IC50 value of 5.1 (±0.2) µM and 3.2 (±0.4) μM, respectively, against methicillin-resistant Staphylococcus aureus.

No MeSH data available.


Related in: MedlinePlus