Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: The first total synthesis of leopolic acid A, a fungal metabolite with a rare 2,3-pyrrolidinedione nucleus linked to an ureido dipeptide, was designed and carried out. Crucial steps for the strategy include a Dieckmann cyclization to obtain the 2,3-pyrrolidinedione ring and a Wittig olefination to install the polymethylene chain. An oxazolidinone-containing leopolic acid A analogue was also synthesized. The antibacterial activity showed by both compounds suggests that they could be considered as promising candidates for future developments.

SUBMITTER: Dhavan AA

PROVIDER: S-EPMC4979754 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

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

Dhavan Atul A AA Kaduskar Rahul D RD Musso Loana L Scaglioni Leonardo L Martino Piera Anna PA Dallavalle Sabrina S

Beilstein journal of organic chemistry 20160729

The first total synthesis of leopolic acid A, a fungal metabolite with a rare 2,3-pyrrolidinedione nucleus linked to an ureido dipeptide, was designed and carried out. Crucial steps for the strategy include a Dieckmann cyclization to obtain the 2,3-pyrrolidinedione ring and a Wittig olefination to install the polymethylene chain. An oxazolidinone-containing leopolic acid A analogue was also synthesized. The antibacterial activity showed by both compounds suggests that they could be considered as ...[more]

PMID: 27559415

Similar Datasets

Total synthesis and antimicrobial evaluation of natural albomycins against clinical pathogens.

Project description:Development of effective antimicrobial agents continues to be a great challenge, particularly due to the increasing resistance of superbugs and frequent hospital breakouts. There is an urgent need for more potent and safer antibiotics with novel scaffolds. As historically many commercial drugs were derived from natural products, discovery of antimicrobial agents from complex natural product structures still holds a great promise. Herein, we report the total synthesis of natural albomycins δ1 (1a), δ2 (1b), and ε (1c), which validates the structures of these peptidylnucleoside compounds and allows for synthetic access to bioactive albomycin analogs. The efficient synthesis of albomycins enables extensive evaluations of these natural products against model bacteria and clinical pathogens. Albomycin δ2 has the potential to be developed into an antibacterial drug to treat Streptococcus pneumoniae and Staphylococcus aureus infections.

| S-EPMC6123416 | biostudies-literature

Synthesis and Antimicrobial Activity of Novel Piperidinyl Tetrahydrothieno[2,3-c]isoquinolines and Related Heterocycles.

Project description:A novel series of 1-amino-2-substituted-5-piperidinyl-6,7,8,9-tertahydrothieno[2,3-c]isoquinolines (4a-e) was synthesized upon treatment of 4-cyano-1-piperidinyl-5,6,7,8-tetrahydroisoquinline-3(2H)-thione (2) with ?-halo carbonyl compounds such as chloroacetone, ethyl chloroacetate, 2-bromoacetophenone, chloroacetamide, and chloroacetanilide. Construction the pyrrolyl ring associated with the thienotetrahydroisoquinoline moiety was achieved by treatment of compounds 4a, b with 2,5-dimethoxytertahydrofuran in acetic acid. 1-Pyrrolyl-2-substituted-thieno[2,3-c]isoquinolines 5a and 5b which in turn were used as multipurpose precursors for synthesis of other new heterocycles. Assignments of the chemical structures of the respectively synthesized thienotetrahydroisoquinolines and their derivatives were established on the bases of elemental and spectral techniques (Fourier transform infrared, 1H NMR, 13C NMR, and mass spectroscopy). Furthermore, certain compounds were screened for their antimicrobial activity which revealed promising activities against various pathogenic strains of bacteria and fungi.

| S-EPMC6964266 | biostudies-literature

Design, synthesis and antimicrobial activity of usnic acid derivatives.

Project description:Usnic acid, a dibenzofuran, was originally isolated from lichens producing secondary metabolites, and is well known as an antibiotic, but is also endowed with several other interesting properties. Thus, the goal of this paper is the design of new usnic acid derivatives and evaluation of their antimicrobial activity. All newly synthesized compounds possess good antibacterial activity with MIC ranging from 1.02-50.93 × 10-2 mmol mL-1 and MBC from 2.05-70.57 × 10-2 mmol mL-1. The most sensitive bacterial species was Staphylococcus aureus, while Pseudomonas aeruginosa and Escherichia coli were the most resistant among the ATCC strains, and MRSA was the most resistant among all tested bacteria (ATCC and clinical isolates). Their antifungal activity was very strong (MIC = 0.35-7.53 × 10-2 mmol mL-1 and MFC = 0.70-15.05 × 10-2 mmol mL-1) - better than those of reference compounds and usnic acid itself. The most sensitive fungal species was Trichoderma viride, while Penicillium versicolor var. cyclopium appeared to be the most resistant. It should be mentioned that in general most of the compounds showed weaker antibacterial activity, but better antifungal properties than usnic acid itself. The results allow us to conclude that the title compounds are good lead compounds for novel more active antibacterial drugs. On the other hand, these compounds are very promising as antifungals.

| S-EPMC6072497 | biostudies-literature

Concise Total Synthesis and Antifungal Activities of Fusaric Acid, a Natural Product.

Project description:The total synthesis of a natural product alkaloid fusaric acid (FA), which exhibits herbicide, fungicide, insecticide and even diverse notable pharmacological activities, was accomplished in four steps using commercially available materials. The synthesis, based on a unified and flexible strategy using 6-bromonicotinaldehyde as a common intermediate, is concise, convergent, practical and can be carried out on a two-gram scale. This approach could be readily applicable to the synthesis of its analogues. In addition, FA had a wide range of inhibitory activities against 14 plant pathogenic fungi in this study, which demonstrated that as a leading compound, and it has great potential to be further developed as an agricultural fungicide.

| S-EPMC7503603 | biostudies-literature

Total synthesis and structure-activity investigation of the marine natural product neopeltolide.

Project description:The total synthesis and biological evaluation of neopeltolide and analogs are reported. The key bond-forming step utilizes a Lewis acid-catalyzed intramolecular macrocyclization that installs the tetrahydropyran ring and macrocycle simultaneously. Independent of each other, neither the macrolide nor the oxazole side chain substituents of neopeltolide can inhibit the growth of cancer cell lines. The biological data of the analogs indicate that alterations to either the ester side chain or the stereochemistry of the macrolide result in a loss of biological activity.

| S-EPMC2735232 | biostudies-literature

Synthesis and antimicrobial activity of amino acid and peptide derivatives of mycophenolic acid.

Project description:The series of 16 novel amino acid and peptide mycophenolic acid (MPA) derivatives was obtained as potential antibacterial agents. Coupling of MPA with respective amines was optimized with condensing reagents such as EDCI/DMAP and T3P/TEA. Amino acid analogs were received both as methyl esters and also with the free carboxylic group. The biological activity of the products was tested on five references bacterial strains: Klebsiella pneumoniae ATCC 700603 (ESBL), Escherichia coli ATCC 8739, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus MRSA ATCC 43300, Staphylococcus aureus MSSA ATCC 25923. Peptide derivatives proved to be the most versatile ones, their MIC values relative to most strains was lower than MPA alone. It has been noted that the activity of amino acid derivatives depends on the configuration at the chiral center in the amino acid unit and methyl esters indicated better antimicrobial activity than analogs with free carboxylic group.

| S-EPMC7173178 | biostudies-literature

Total synthesis of the natural (-)-205B alkaloid and its activity toward α7 nAChRs.

Project description:A new approach to the synthesis of the (-)-205B alkaloid is described in this paper. This work is characterised by the development of an efficient chirality transfer through a silyl tethered intramolecular alkylation reaction, an unprecedented tandem highly selective iridium catalyzed partial reduction of lactam coupled with an acid promoted aza-Prins reaction, and an almost complete stereochemical control in Shenvi's radical hydrogen atom transfer on an exocyclic methylene. The second part of this work demonstrates the positive allosteric behavior of this natural alkaloid toward α7 nAChRs, in contrast to the reported inhibitory effect of the unnatural enantiomer.

| S-EPMC9972826 | biostudies-literature

Synthesis of Pyrazole-Thiobarbituric Acid Derivatives: Antimicrobial Activity and Docking Studies.

Project description:A one-pot reaction was described that results in various pyrazole-thiobarbituric acid derivatives as new pharmacophore agents. These new heterocycles were synthesized in high yields with a broad substrate scope under mild reaction conditions in water mediated by NHEt?. The molecular structures of the synthesized compounds were assigned based on different spectroscopic techniques. The new compounds were evaluated for their antibacterial and antifungal activity. Compounds 4h and 4l were the most active compounds against C. albicans with MIC = 4 µg/L. Compound 4c exhibited the best activity against S. aureus and E. faecalis with MIC = 16 µg/L. However, compounds 4l and 4o were the most active against B. subtilis with MIC = 16 µg/L. Molecular docking studies for the final compounds and standard drugs were performed using the OpenEye program.

| S-EPMC6274314 | biostudies-literature

Total chemical synthesis of glycocin F and analogues: S-glycosylation confers improved antimicrobial activity.

Project description:Glycocin F (GccF) is a unique diglycosylated bacteriocin peptide that possesses potent and reversible bacteriostatic activity against a range of Gram-positive bacteria. GccF is a rare example of a 'glycoactive' bacteriocin, with both the O-linked N-acetylglucosamine (GlcNAc) and the unusual S-linked GlcNAc moiety important for antibacterial activity. In this report, glycocin F was successfully prepared using a native chemical ligation strategy and folded into its native structure. The chemically synthesised glycocin appeared to be slightly more active than the recombinant material produced from Lactobacillus plantarum. A second-generation synthetic strategy was used to prepare 2 site selective 'glyco-mutants' containing either two S-linked or two O-linked GlcNAc moieties; these mutants were used to probe the contribution of each type of glycosidic linkage to bacteriostatic activity. Replacing the S-linked GlcNAc at residue 43 with an O-linked GlcNAc decreased the antibacterial activity, while replacing O-linked GlcNAc at position 18 with an S-linked GlcNAc increased the bioactivity suggesting that the S-glycosidic linkage may offer a biologically-inspired route towards more active bacteriocins.

| S-EPMC5890784 | biostudies-literature

Total synthesis and biological evaluation of the tetramic acid based natural product harzianic acid and its stereoisomers.

Project description:The bioactive natural product harzianic acid was prepared for the first time in just six steps (longest linear sequence) with an overall yield of 22%. The identification of conditions to telescope amide bond formation and a Lacey-Dieckmann reaction into one pot proved important. The three stereoisomers of harzianic acid were also prepared, providing material for comparison of their biological activity. While all of the isomers promoted root growth, improved antifungal activity was unexpectedly associated with isomers in the enantiomeric series opposite that of harzianic acid.

| S-EPMC4737532 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data