N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• t-BuOH and LiBr as additives [102]. The isopropyl-substituted derivative 84 was easily converted into the corresponding methylene lactam 85, upon removal of the sulfinyl unit under acidic conditions. Finally, ozonolysis of 85 yielded tetramic acid 86 in 60% yield (Scheme 26). The configuration of

• the newly generated chiral center in compounds 84 was assigned from the sign of the optical rotation of enantioenriched tetramic acid 86, which was previously characterized. Based on this, it can be stated that addition of the allenoate 83 takes place mainly to the Re face of imines with (RS

Microwave-assisted efficient and facile synthesis of tetramic acid derivatives via a one-pot post-Ugi cascade reaction

• Yong Li,
• Zheng Huang,
• Jia Xu,
• Yong Ding,
• Dian-Yong Tang,
• Jie Lei,
• Hong-yu Li,
• Zhong-Zhu Chen and
• Zhi-Gang Xu

Beilstein J. Org. Chem. 2020, 16, 663–669, doi:10.3762/bjoc.16.63

• University of Arts and Sciences, Chongqing 402160, China Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA 10.3762/bjoc.16.63 Abstract A facile microwave-assisted method for the synthesis of tetramic acid derivatives has been

• developed through an Ugi/Dieckmann cyclization strategy with DBU. This two-step one-pot procedure afforded the targeted tetramic acid analogues in good yields. With commercially available Ugi starting materials, microwave irradiation, a simple operation, excellent yields, and a broad scope, this reaction

• has the potential to produce a large number of tetramic acid analogues, which cannot be easily accessed by the classic synthetic methods. Keywords: Dieckmann cyclization; multicomponent reactions; nitrogen heterocycles; one-pot reaction; Ugi reaction; Introduction Nitrogen-containing heterocycles

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

• of a linear precursor to obtain the desired 3-alkyl-substituted tetramic acid core. The synthesized analogue is more effective than the parent leopolic acid A against Gram-positive (Staphylococcus pseudintermedius) and Gram-negative (E. coli) bacteria (MIC 8 µg/mL and 64 µg/mL, respectively

• class of antibacterial agents active also against resistant strains. Keywords: antimicrobial activity; multidrug-resistant bacteria; natural products; synthesis; tetramic acid; Introduction The treatment of bacterial infections by antibiotics is widely regarded as one of the major achievements of the

• acid A analogue containing the tetramic acid moiety in place of the 2,3-pyrrolidinone ring (compound 1), while maintaining unchanged all the other structural features of the natural compound. The advantage of this substitution should be a higher stability of the heterocyclic ring, hopefully coupled

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

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• ]. Macrocidin A (19) and macrocidin B (20) [64] belong to a family of plant pathogens produced by Phoma macrostoma, a microorganism parasitic to Canadian thistle. Macrocidins contain a tetramic acid group in their skeleton and show selective herbicidal activity on broadleaf weeds but do not affect grasses

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

• ] variant of Lacey–Dieckmann [8] condensation (Scheme 1) [9][10]. Reaction of either β-ketoester 4 or Meldrum’s acid derivative 9 with suitably protected glycine esters (5,6,10), followed by base-induced condensation furnished the desired tetramic acid model compounds as crystalline solids after treatment

• DMB group with CAN [17] produced no product either. Successful removal of the DMB-protecting group from hydroxylated tetramic acid 16 and (trimethylsilyl)ethyl hemiaminal 19 was achieved upon treatment with an excess of DDQ in wet DCM. Treatment of the N-allyl-protected compound using catalytic

• organic phase was purified with preparative HPLC (Machery Nagel, Nucleodur VP250/21 C18 Gravity, 5 µm; 280 nm; 90:10 MeCN/(H2O + 1% formic acid); 10 mL/min) to give the corresponding 5-hydroxy-3-cyclohexanecarbonyl tetramic acid as a white solid. Naturally occurring 5-hydroxylated 3-acyltetramic acids

Synthesis of the spiroketal core of integramycin

• Evgeny. V. Prusov

Beilstein J. Org. Chem. 2013, 9, 2446–2450, doi:10.3762/bjoc.9.282

• products with tetramic acid fragments we embarked on the development of a concise and modular approach towards integramycin and related natural products. According to the retrosynthetic analysis, which is outlined in Figure 2, the target molecule may be assembled from an appropriate spiroketal advanced

• by an intramolecular Diels–Alder cycloaddition. The installation of the tetramic acid moiety would proceed via Lassey–Dickmann condensation with subsequent introduction of the 5-hydroxy group by oxidation of the corresponding vinylogous enolate. Herein a straightforward synthesis of the C16–C35

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

• inhibitory activity) [7] and unnatural systems, such as 3-carboxamide tetramic acid 1c and 3-carboxamide piperidine-2,4-dione 1d (undecaprenyl pyrophosphate synthase (UPPS) inhibitory activity) [8] exhibit high levels of antibacterial activity (Figure 1). All these systems share a β-dicarbonyl core. A drug

• discovery programme inspired by these natural products, as promoted by Waldmann [9], was of interest to us. We have recently focused on the construction and evaluation of libraries derived from tetramic acid scaffolds and discovered that bicyclic 3-carboxamide 1e, bicyclic 3-acyl 1f and monocyclic 3-acyl 1g

• , tautomeric behaviour and antibiotic activity of related monocyclic 3-carboxamide tetramic acid systems 2 and 3 (Schemes 1–3), the results of which are outlined below. In system 2, the N(1) and C(5) substituents were chosen in order to probe the effect of the length of the N-alkyl chain on antibiotic activity

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

• . In continuation of this work, we have synthesised dienyl tetramic acid derivatives. Results 5,6-O-Isopropylidene-ascorbic acid on reaction with DBU led to the formation of tetronolactonyl allyl alcohol, which on oxidation with pyridinium chlorochromate gave the respective tetranolactonyl allylic

• aldehydes. Wittig olefination followed by reaction of the resulting tetranolactonyl dienyl esters with different amines resulted in the respective 5-hydroxy lactams. Subsequent dehydration of the hydroxy lactams with p-toluene sulphonic acid afforded the dienyl tetramic acid derivatives. All reactions were

• performed at ambient temperature and the yields are good. Conclusion An efficient and practical method for the synthesis of dienyl tetramic acid derivatives from inexpensive and easily accessible ascorbic acid has been developed. The compounds bear structural similarities to the tetramic acid based polyenic