ABSTRACT
Oxidation of 3- and 4-pentafluorosulfanyl-substituted anisoles and phenols with hydrogen peroxide and sulfuric acid provided a mixture of SF5-substituted muconolactone, maleic, and succinic acids. A plausible mechanism for the formation of the aliphatic SF5 compounds was presented and their chemical reactivity was investigated. SF5-substituted para-benzoquinone was synthesized; its oxidation led to an improved yield of 2-(pentafluorosulfanyl)maleic acid. The reaction of SF5-substituted maleic anhydride and para-benzoquinone with cyclopentadiene afforded the Diels-Alder adducts. Decomposition of 3-(pentafluorosulfanyl)muconolactone in acidic, neutral and basic aqueous media was investigated and the decarboxylation of 2-(pentafluorosulfanyl)maleic acid provided 3-(pentafluorosulfanyl)acrylic acid.
ABSTRACT
ß-Sitosterol and betulinic acid were used in designing their conjugates with selected polyamines bearing either an amide bond, or an ester and an amide bond simultaneously in the target molecule. The synthesized compounds were subjected to basic cytotoxic and antimicrobial tests. The synthetic protocol is described separately for each of the three series of the target amides, because each series of compounds required a different synthetic approach. The cytotoxicity was tested on cells derived from human T-lymphoblastic leukemia, breast adenocarcinoma and cervical cancer, and compared with the tests on normal human fibroblasts. Most of the target compounds (5a-5c, 11a-11c and 16a-16c) showed medium to high cytotoxicity (0.7-7.8 µM), however, in some cases the compounds showed high cytotoxicity even toward normal human fibroblasts (11a-11c). Two compounds of this series (11c and 16c) also displayed antimicrobial activity with high and selective microbe specificity. The compound 11c was potent against Escherichia coli (minimal inhibition concentration (MIC) 6.25 µg mL(-1), i.e. 9.75 nM mL(-1)) and Staphylococcus aureus (MIC 12.5 µg mL(-1), i.e. 19.5 nM mL(-1)), and showed medium activity against Pseudomonas aeruginosa. The compound 16c was highly active against Enterococcus faecalis and S. aureus (both, MIC 3.125 µg mL(-1), i.e. 4.22 nM mL(-1)), both Gram-positive bacteria, however showed only weak activity against E. coli and no activity against P. aeruginosa, both Gram-negative bacteria, which indicates possible microbe specificity of 16c. Comparing ß-sitosterol-based series (5a-5c) and betulinic acid series (11a-11c and 16a-16c) of the target compounds, the latter one gave more promising structures. The compounds 11c and 16c showed effects which may be described as multifarious activity (pleiotropic effects).
Subject(s)
Anti-Bacterial Agents/chemistry , Polyamines/chemistry , Sitosterols/chemistry , Triterpenes/chemistry , Anti-Bacterial Agents/pharmacology , Cell Survival/drug effects , Escherichia coli/drug effects , HeLa Cells , Humans , MCF-7 Cells , Microbial Sensitivity Tests , Pentacyclic Triterpenes , Polyamines/toxicity , Pseudomonas aeruginosa/drug effects , Sitosterols/pharmacology , Staphylococcus aureus/drug effects , Triterpenes/pharmacology , Betulinic AcidABSTRACT
4-(Pentafluorosulfanyl)catechol, 2-amino-4-(pentafluorosulfanyl)phenol, and 2-amino-5-(pentafluorosulfanyl)phenol undergo oxidation by lead tetraacetate at ambient temperature leading to dearomatization and the formation of SF5-substituted nitriles and esters of cis,cis-hexa-2,4-dienedioic (muconic) acid in good yields. 4-(Pentafluorosulfanyl)phenol and 4-(pentafluorosulfanyl)anisole are oxidized by 30% aqueous hydrogen peroxide in concentrated sulfuric acid to provide 2-(5-oxo-3-(pentafluorosulfanyl)-2,5-dihydrofuran-2-yl)acetic acid [3-(pentafluorosulfanyl)muconolactone] and small amounts of side products--SF5-containing maleic and succinic acids. The methods presented are the first examples of the practical synthesis of aliphatic SF5-containing compounds from readily available aromatic ones.
Subject(s)
Aniline Compounds/chemistry , Anisoles/chemistry , Catechols/chemistry , Fluorides/chemistry , Fluorides/chemical synthesis , Furans/chemical synthesis , Hydrogen Peroxide/chemistry , Lactones/chemical synthesis , Phenols/chemistry , Sulfur Compounds/chemistry , Sulfur Compounds/chemical synthesis , Furans/chemistry , Lactones/chemistry , Oxidation-ReductionABSTRACT
Three new polyamine conjugates with stigmasterol [(3ß,22E)-stigmasta-5,22-dien-3-ol] were synthesized and subjected to basic antimicrobial and cytotoxic tests. The conjugate derived from spermine, (3ß,22E)-stigmasta-5,22-dien-3-yl 4(12-amino-4,9-diaza-dodecylamino)-4-oxobutanoate (5c), displayed considerable antimicrobial activity on Staphylococcus aureus at low concentration (50 µg mL(-1)). The cytotoxic activity was tested on cells of human T-lymfoblastic leukemia (IC(50)=35.8 ± 10.3 µM (5c) and IC(50)=35.9 ± 5.7 µM (5b)) and normal human fibroblasts (IC(50)=38.0 ± 2.8 µM (5c) and IC(50)=45.5 ± 1.9 µM (5b)). Conjugate 5a displayed no activity in both tests.
Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Polyamines/chemistry , Stigmasterol/chemistry , Stigmasterol/pharmacology , Anti-Bacterial Agents/chemical synthesis , Antineoplastic Agents/chemical synthesis , Carboxylic Acids/chemistry , Cell Line, Tumor , Chemical Phenomena , Dose-Response Relationship, Drug , Drug Design , Humans , Models, Molecular , Molecular Conformation , Staphylococcus aureus/drug effects , Stigmasterol/chemical synthesisABSTRACT
Nucleophilic aromatic substitution of the nitro group of para- and meta-nitro-(pentafluorosulfanyl)benzene with alkoxides and thiolates generates a range of substituted 4- and 3-(pentafluorosulfanyl)benzenes in a single-step reaction.
