Total synthesis of the antibacterial polyketide natural product thailandamide lactone

Stereoselective total synthesis of the structurally intriguing polyketide natural product thailandamide lactone was accomplished, and done so using a convergent approach for the first time to the best of our knowledge. The key features of this synthesis included use of a Crimmins acetate aldol reaction, Evans methylation, Urpi acetal aldol reaction, Sharpless asymmetric epoxidation and subsequent γ-lactonization for the installation of six asymmetric centers and the use of the Negishi reaction, Julia-Kocienski olefination, cross metathesis, HWE olefination and intermolecular Heck coupling for construction of a variety of unsaturated linkages. Pd(i)-based Heck coupling was introduced, for the first time to the best of our knowledge, quite efficiently to couple the major eastern and sensitive western segments of the molecule. The antibacterial activity of thailandamide lactone was also evaluated.

A convergent strategy for the total synthesis of the structurally intriguing polyketide natural product thailandamide lactone has been developed for the first time. The antibacterial activity of the molecule has also been disclosed.     

Sucrose ester micellar-mediated synthesis of Ag nanoparticles and the antibacterial properties

Ag nanoparticles with diameter in the range of 10–25 nm had been synthesized using a simple sucrose ester micellar-mediated method. Ag nanoparticles were formed by adding AgNO₃ solution into the sucrose ester micellar solution containing sodium hydroxide at atmospheric condition after 24 h of aging time. Trace amount of dimethyl formamide (DMF) in the sucrose ester solution served as a reducing agent while NaOH acted as a catalyst. The produced Ag nanoparticles were highly stable in the sucrose ester micellar system as there was no precipitation after 6 months of storage. The as-synthesized Ag nanoparticles were characterized using transmission electron microscope (TEM), X-ray diffractometer (XRD), dynamic light scattering (DLS) and UV–vis spectroscopy (UV–vis). Formation mechanism of Ag nanoparticles in the micellar-mediated synthesis is postulated. The antibacterial properties of the Ag nanoparticles were tested against Methicillin-resistant Staphylococcus aureus (MRSA) (Gram-positive) and Aeromonas hydrophila (Gram-negative) bacteria. This work provides a simple and “green” method for the synthesis of highly stable Ag nanoparticles in aqueous solution with promising antibacterial property.     

Design and synthesis of novel thiourea metal complexes with controllable antibacterial properties

A new bidentate O,S donor thiourea ligand (L¹), namely N‐(2‐hydroxyethyl)‐N′‐2‐chlorobenzoylthiourea, and its oxazolidine derivative (L²) were synthesized. Derivative L² was used for the preparation of Ni(L²)₂ and Cu(L²)₂ complexes. The compounds were investigated using X‐ray crystallography and Fourier transform infrared, ¹H NMR and UV–visible spectroscopies. Single‐crystal X‐ray analysis showed strong hydrogen bonding interactions between carbonyl oxygen and N(10) ─ H in the L¹ ligand. In addition, the antibacterial activities of these compounds were evaluated against Gram‐positive and Gram‐negative bacteria, measured using the colony count method. The Cu(L²)₂ complex exhibited a significant antibacterial activity while the activity of the other compounds was much lower. Finally, the relationship between the structure and antibacterial properties of these compounds was investigated using highest occupied and lowest unoccupied molecular orbital energies calculated by density functional theory method based on the 6‐31G*/LANL2DZ basis set.     

Total synthesis of the turrianes and evaluation of the DNA-cleaving properties

The first total synthesis of three naturally occurring cyclophane derivatives belonging to the turriane family of natural products is described. Their sterically hindered biaryl entity is formed by reaction of the Grignard reagent derived from aryl bromide 10 with the oxazoline derivative 18, and the macrocyclic tether of the targets is efficiently forged by ring closing metathesis. While conventional RCM catalyzed by the ruthenium-carbene complexes 33 or 34 invariably leads to the formation of mixtures of both stereoisomers with the undesirable (E)-alkene prevailing, ring closing alkyne metathesis (RCAM) followed by Lindlar reduction of the resulting cycloalkynes 37 and 38 opens a convenient and stereoselective entry into this class of compounds. RCAM can either be accomplished by using the tungsten alkylidyne complex [(tBuO)3 [triple bond] WCCMe3] or by means of a catalyst formed in situ from [Mo(CO)6] and para-trifluoromethylphenol. The latter method is significantly accelerated when carried out under microwave heating. Furthermore, the judicious choice of the protecting groups for the phenolic -OH functions turned out to be crucial. PMB-ethers were found to be compatible with the diverse reaction conditions en route to 3-5; their cleavage, however, had to be carried out under carefully optimized conditions to minimize competing O-C PMB migration. Turrianes 3-5 are shown to be potent DNA cleaving agents under oxidative conditions when administered in the presence of copper ions.     

Metal-based antibacterial and antifungal sulfonamides: synthesis,characterization, and biological properties

Some furanyl-derived sulfonamides and their cobalt(II), copper(II), nickel(II), and zinc(II) complexes have been synthesized. The structural formulae of the complexes have been inferred by using physico-chemical and spectroscopic methods. The new sulfonamides behave as bidentate ligands in complexation with the metals and an octahedral geometry has been suggested for all these complexes. Both the free sulfonamides and their complexes have been screened for their in vitro antibacterial and antifungal activities against a number of bacteria and fungi. In vitro cytotoxic properties of all the compounds were also studied using brine shrimp bioassay.     

Biomimetic synthesis, antibacterial activity and structure-activity properties of the pyroglutamate core of oxazolomycin

Biomimetic intramolecular aldol reactions on oxazolidine templates derived from serine may be used to generate densely functionalised pyroglutamates, which are simpler mimics of the right hand side of oxazolomycin. Some of the compounds from this sequence exhibit in vivo activity against S. aureus and E. coli, suggesting that pyroglutamate scaffolds may be useful templates for the development of novel antibacterials, and cheminformatic analysis has been used to provide some structure-activity data.     

Total synthesis and properties of the crambescidin core zwitterionic acid and crambescidin 359

The total synthesis of the crambescidin core acid 9, crambescidins 359 (8) and 431 (7), and the properties of the crambescidin core are described. A key step of the synthetic route to guanidinium carboxylate 9 is Pd(0) catalyzed cleavage of the ester side chain of pentacyclic cinnamyl ester 15. This ester is also employed to prepare a small library of crambescidin alkaloid analogues that differ in their C14 side chain. The zwitterionic guanidinium carboxylate 9 was shown to readily decarboxylate to form crambescidin 359 (8). Decarboxylation of crambescidin core acid 9 was fastest under basic conditions. In the presence of base, up to eight deuterium atoms can be incorporated into the pentacyclic crambescidin core. Both deuterium incorporation and decarboxylation of crambescidin core acid 9 are the result of facile ring opening of the spirocyclic ether rings of the pentacyclic guanidinium moiety.     

Green synthesis and antibacterial activity of chalcogenoesters

Herein, we present a new variation for an eco-friendly methodology for the synthesis of chalcogenoester in good-to-excellent yields in a short time, with an easy work-up/purification step, and in a greenest methodology, affording the minimum generation of solid and liquid waste, in comparison to that described in the literature. Additionally, some selected compounds were evaluated as antimicrobial agents, showing moderate activity against a variety of microorganisms including the K. pneumoniae, P. aeruginosa and also some selected fish pathogenic bacteria.     

Cationic poly(ester‐phosphoester)s: Facile synthesis and antibacterial properties

Biodegradable poly(ester‐phosphoester)s bearing multiple chloroethyl groups were synthesized facilely by the ring‐opening copolymerization of 2‐(2‐chloroethoxy)‐2‐oxo‐1,3,2‐dioxaphospholane (CEP) and ε‐caprolactone (CL) in the presence of lanthanum tris(2,6‐di‐tert‐butyl‐4‐methylphenolate)s (La(DBMP)₃) as single‐component catalyst under mild conditions. Then the quaternization reaction was carried out between the halide copolymers and a series of N,N‐dimethyl alkylamines to give poly(ester‐phosphoester)s containing ammonium groups with various charge density and alkyl chain length. The antibacterial properties of these cationic poly(esterphosphoester)s were evaluated by OD600 and zone of inhibition methods against gram‐negative (Escherichia coli) and gram‐positive (Staphylococcus aureus) bacteria. Cationic poly(esterphosphoester)s with long alkyl chain on the ammonium groups show excellent antibacterial activity for both gram‐negative and gram‐positive bacteria even with low charge density. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3667–3673     

Polysiloxane cationic biocides with imidazolium salt (ImS) groups, synthesis and antibacterial properties

Novel polysiloxanes with pendant biocidal N,N′-dialkylimidazolium salt (ImS) groups were synthesized and compared with polysiloxanes bearing conventional biocidal quaternary ammonium salt (QAS) groups. The bacteriostatic power of these polymers was tested and compared under the same conditions in aqueous solution against two common strains of Gram positive bacteria and three strains of Gram negative bacteria. These new ImS containing polymers exhibited high antibacterial potency against all bacteria studied, similar to those substituted with QAS groups. The advantage of the imidazolium substituted polysiloxane stems from its higher thermal stability, as compared with the quaternary alkylammonium functionalized polymer, as demonstrated by thermogravimetric studies.     

Salicylanilide acetates: synthesis and antibacterial evaluation

A new series of salicylanilide acetates was synthesized and evaluated for their in vitro antifungal and antituberculotic activity. Some of the evaluated compounds possessed comparable or better antifungal activity than a fluconazole standard. All these compounds exhibited very good potential and their in vitro activity against drug resistant and sensitive clinical isolates of Mycobacteria were found to be equivalent or better than a standard of isoniazide, a well-known first-line drug for tuberculosis treatment.     

Total synthesis of iso- and bongkrekic acids: natural antibiotics displaying potent antiapoptotic properties

For over five decades, owing to their antiapoptotic activities, bongkrekic and isobongkrekic acids have generated interest from the scientific community. Here, we disclose full details of our investigation into the synthesis of isobongkrekic acid, which culminated in its first preparation and features various palladium-catalysed cross-couplings and Takai olefination reactions. Access to bongkrekic acid is also reported by this route. These syntheses involve the preparation and use of new general building blocks which could find wider applications.     

Total synthesis of himandravine

[reaction: see text] The first total synthesis of (+)-himandravine (1) is described, starting from (2S,6S)-cis-2-formyl-6-methyl-N-Boc-piperidine (8) in 11 linear steps and 17% overall yield. The key step involves a highly diastereoselective intramolecular Diels-Alder reaction of the key intermediate 5 that contains the entire latent carbon framework and functional group substitution of himandravine.     

Total synthesis of cis-solamin

[structure: see text] A convergent total synthesis of cis-solamin and its diastereomer was accomplished using VO(acac)2-catalyzed diastereoselective epoxidation followed by cyclization of bis-homoallylic alcohol as the key step. By comparison of the optical rotation of two possible diastereomers, it is suggested that the absolute configuration of natural cis-solamin is 1a.     

Total synthesis of fuzinoside

The first total syntheses of fuzinoside (1b) were achieved from d-galactose through two strategies (BCA and ABC) in 11 (total yield: 5.0%) and 15 (total yield: 3.7%) steps, respectively. Comparison of NMR data of synthetic compound 1b and those of the fuzinoside isolated from the lateral roots of Aconitum carmicaelii suggests that the structure reported in the literature ^1 and 2 might not be accurate. The synthetic fuzinoside (1b) exhibited moderate cardiac activity in the isolated bullfrog heart assay.     

Total synthesis of gymnocin-A

A highly convergent total synthesis of gymnocin-A, a cyctotoxic polyether marine natural product, has been achieved. The synthesis features Suzuki-Miyaura coupling of the ABCD and FGHIJKLMN rings, stereoselective introduction of the C17 hydroxyl group, ring-closure of the F ring, and a late-stage incorporation of a 2-methyl-2-butenal side chain.     

Total synthesis of dysiherbaine

A convergent total synthesis of the marine natural product dysiherbaine was accomplished. The key steps of the synthesis are an alkylation at the gamma-carbon of a protected glutamate with a highly substituted pyran derived from mannose, which was followed by a ring-contraction cascade reaction, which simultaneously gave the tetrasubstituted carbon and the hexahydrofuro[3,2-b]pyran ring system of the natural product.