Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• intermediates being unstable [4]. In light of these results, we intended to investigate the role of the 2,3 pyrrolidinedione ring by replacing it with a more stable isomeric 2,4-pyrrolidinedione moiety. Actually, 2,4 pyrrolidinediones (tetramic acids) have recently attracted considerable attention for their

• appears well suited to a convergent synthetic approach based around two fragments, the ureido dipeptide L-Phe-L-Val and the 3-decyltetramic acid core (Figure 1). Initially, we focused on the synthesis of the 2,4-pyrrolidinedione core. A review of the existing literature on tetramic acids syntheses

• revealed a considerable amount of papers regarding the preparation of 3-acyltetramic acids [14][15][16][17][18], whereas the synthesis of 3-alkyl-tetramic acids has been considerably less investigated [19][20][21][22]. We envisaged that the most straightforward route to the 2,4-pyrrolidinedione system

Total synthesis of leopolic acid A, a natural 2,3-pyrrolidinedione with antimicrobial activity

• Atul A. Dhavan,
• Rahul D. Kaduskar,
• Loana Musso,
• Leonardo Scaglioni,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2016, 12, 1624–1628, doi:10.3762/bjoc.12.159

• residue, which in turn, is connected to the ureido dipeptide L-Phe-L-Val. The compound showed antifungal and antibacterial activity against Mucor hiemalis and Staphylococcus aureus with a MIC of 32 and 16 μg/mL, respectively [2]. Compounds containing the isomeric 2,4-pyrrolidinedione ring system (tetramic

• acids) are widespread among the fungal metabolites and show a number of biological activities, i.e., antibacterial, antiviral, antifungal and anticancer. More than one hundred of them have been isolated from a variety of natural sources [3]. Conversely, natural compounds with a simple 2,3

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

A simple and efficient method for the preparation of 5-hydroxy-3-acyltetramic acids

• Johanna Trenner and
• Evgeny V. Prusov

Beilstein J. Org. Chem. 2015, 11, 323–327, doi:10.3762/bjoc.11.37

• oxygen is reported. The deprotection of the resulting compounds was also achieved. Keywords: heterocyclic chemistry; hydroxylation; natural products; tetramic acids; Findings 5-Hydroxy-3-acyltetramic acid is an unusual structural element which is found in the molecules of such biologically active

• the reaction was essentially complete in 20 minutes according to TLC analysis. Oxidation reactions performed in polar aprotic solvents, such as DMPU and DMF, gave significantly lower yields compared to THF. As with the parent tetramic acids, isolation and purification of the hydroxylated derivatives

• was only possible by means of preparative HPLC. Similar results were obtained for the N-DMB and N-allyl protected tetramic acids, though the best yield of compound 16 was obtained when LDA was employed as a base (Table 3). The obtained hydroxylated tetramic acids can readily be transformed to

Synthesis and antibacterial activity of monocyclic 3-carboxamide tetramic acids

• Yong-Chul Jeong and
• Mark G. Moloney

Beilstein J. Org. Chem. 2013, 9, 1899–1906, doi:10.3762/bjoc.9.224

• ) tetramic acids (Figure 2) have been found to exist as a pair of external conformers (AB and CD) in slow equilibrium (ABCD), each consisting of a pair of internal tautomers in rapid equilibrium (AB and CD). The tautomerisation of 3-acyltetramic acids has been shown to be mainly affected by substitution on N

• Gram-negative bacteria, no activity against E. coli and P. aeruginosa was found (MIC > 64 µg/mL, data not shown), consistent with the inactivity of 3-acyl and 3-carboxamide tetramic acids against these strains seen earlier [7][8][10]. This result is most likely explained by their poor cell permeability

• potential for optimisation. According to Figure S1, strongly active compounds can be found at c log P values of 1–2, 3 or 4, and for the highly susceptible strain H4, for example, compounds of interest would be 2b–e and 2g. Conclusion We have prepared monocyclic 3-carboxamide tetramic acids from 3

An efficient synthesis of tetramic acid derivatives with extended conjugation from L-Ascorbic Acid

• Biswajit K. Singh,
• Surendra S. Bisht and
• Rama P. Tripathi

Beilstein J. Org. Chem. 2006, 2, No. 24, doi:10.1186/1860-5397-2-24

• Biswajit K. Singh Surendra S. Bisht Rama P. Tripathi Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow-226001, India 10.1186/1860-5397-2-24 Abstract Background Tetramic acids with polyenyl substituents are an important class of compounds in medicinal chemistry

• . Both solid and solution phase syntheses of such molecules have been reported recently. Thiolactomycin, a clinical candidate for treatment of tuberculosis has led to further explorations in this class. We have recently developed an efficient synthesis of tetramic acids derivatives from L- ascorbic acid

• and are potentially new tuberculosis drugs. 5-Alkenyl tetramic acids, being structurally similar to thiolactomycins, possess anti-HCV and anti-HIV activities [34][35] and are likely to yield new antitubercular prototype compounds active against tuberculosis in HIV cases. We have developed a one-pot