Synthesis of novel 14-membered cyclic bis-semicarbazones

An efficient method for the stereoselective synthesis of novel 14-membered cyclic bis-semicarbazones based on acid-catalyzed cyclization of the hydrazones of 3-(3-oxobutyl)semicarbazides has been developed. The starting semicarbazides were prepared according to a four-step strategy involving amidoalkylation of the sodium enolate of acetylacetone with N-(α-tosylbenzyl)carbamates followed by base-promoted retro-Claisen reaction and treatment of the obtained N-(3-oxobutyl)carbamates with hydrazine.     

Synthesis of a novel 14-membered highly constrained cyclic peptidic scaffold

The synthesis and NMR analysis of a novel highly constrained scaffold is described. The 14-membered macrocyclic ring structure was inspired by many medicinally relevant natural products that also contain the bi-aryl ether moiety. The synthesis required only commercially available starting materials and involved a base mediated S_NAr cyclization. A conformational search was performed, which indicated a strong preference for a single conformation, which was consistent with observed ROE signals by NMR.     

Synthesis of a key intermediate of novel galbonolide analogues via efficient construction of a conjugated diene system

The development of an efficient synthetic method enabled multi-gram synthesis of a key intermediate, which is useful for the modification at the C6-functional group of galbonolide analogues. The structure of a key intermediate including a conjugated diene was afforded by Horner-Emmons reaction, alkylation of Weinreb amide with alkyl lithium and a subsequent Wittig reaction.     

Synthesis and cytotoxic activity of novel curcumin analogues

Five novel curcumin analogues bearing different substituents at 4-position of phenyl group were synthesized. Their structures were confirmed by NMR and HRMS spectrum. Their cytotoxic activities against six tumor cell lines were tested by the standard MTT assay in vitro. The results indicated that four analogues （1A-1C, 1E） with solubilizing moieties showed selective potent cytotoxicity against HepG2, HeLa and CT26 cell lines, and analogue 1A and 1C exhibited more potent cytotoxicity than curcumin against CT26 cell line. It was suggested that introduction of appropriate substituents to 4-position of phenyl group might be a potential option for structural modification of curcumin.     

Synthesis and antitumor activity of novel salvicine analogues

Systematic structure modification of the side train of the lead compound saprothoquinone provides a series of salvicine analogues,fifteen of them were first reported.Some compounds were demonstrated potent cytotoxicity against tumor cells with the 50%inhibition concentration in the micromolar range.Furthermore some compounds showed potent topoisomeraseⅡinhibitory effects.The preliminary structure-activity relationship of saprorthoquinone analogues was discussed according to their cytotoxicity against thr...     

Synthesis of new 14-membered macrolide antibiotics via a novel ring contraction metathesis

[reaction: see text] A novel ring opening ring closing metathesis (ROM-RCM) was demonstrated for cyclic conjugated dienes, effecting the excision of a C(2)H(2) unit and a net ring contraction. Applying the ring contraction metathesis, new 14-membered ring macrolide antibiotics were synthesized in a single step from existing 16-membered ring macrolides. This new class of macrolide antibiotics will provide access to new therapeutics for the treatment of macrolide-resistant bacterial infections.     

Synthesis of cicerfuran, an antifungal benzofuran, and some related analogues

Routes were investigated for the synthesis of cicerfuran, a hydroxylated benzofuran from wild chickpea implicated in resistance to Fusarium wilt, and some of its analogues. A novel method is described for the synthesis of oxygenated benzofurans by epoxidation and cyclisation of 2′-hydroxystilbenes. The stilbene intermediates required could be synthesised by palladium-catalysed coupling of styrenes with mono-oxygenated aryl halides but not with di-oxygenated aryl halides. Stilbenes corresponding to the latter were synthesised by Wittig reactions.     

Synthesis of novel 15-membered macrolide dimers

A series of novel dimers of 15-membered macrolides was synthesized and evaluated.The dimers exhibited excellent activity against erythromycin-susceptible S.pneumonia,but did not show any improved activity against erythromycin-resistant S. pneumoniae encoded by erm gene.     

Synthesis and evaluation of structural requirements for antifungal activity of cyrmenin B1 analogues

In a study aiming to define the structural elements essential to cyrmenin B₁ antifungal activity, the synthesis of a series of analogues was carried out. The structural modification introduced stepwise in distinct areas of the parent molecule allowed a deeper insight to be gained into the most relevant structural features affecting the activity of the natural compound. The bioassay results clearly indicate the relevance of each portion of the parent molecule, only the modification of the conjugated double bond geometry being tolerated.     

Synthesis of novel simplified eleutheside analogues with potent microtubule-stabilizing activity, using ring-closing metathesis as the key-step

The synthesis of a number of novel simplified eleutheside analogues with potent tubulin-assembling and microtubule-stabilizing properties is described, using ring-closing metathesis as the key-step for obtaining the 6-10 fused bicyclic ring system.     

Synthesis of novel 15-membered macrolide derivatives

In order to develop new antibiotics effective against resistant bacteria,a series of novel 15-membered macrolide derivatives were designed and synthesized by the modification of hydroxyl groups at C-11,C-12 and C-4＂ positions.Their structures were confirmed by MS,IR,^1H NMR or ^13C NMR.     

Synthesis and stereochemical elucidation of a 14-membered ring phosphonate

[structure: see text]. We report the synthesis and stereochemical elucidation of a 14-membered ring phosphonate. The key step in the synthesis of the macrolide phosphonate was the cyclization of the acyclic precursor using the Mitsunobu reaction, a mild reaction for the preparation of mixed phosphonates.     

Synthesis of novel analogues of zanamivir as neuraminidase inhibitors

<正>A versatile synthesis of novel zanamivir analogues modified at C-4 and C-8 positions was described.The formation of amides from the acid with corresponding amines,followed by click chemistry generated the triazole substituted compounds as novel analogues of neuraminidase inhibitors in good yields.     

Synthesis, antibacterial activity and quantum-chemical studies of novel 2-arylidenehydrazinyl-4-arylthiazole analogues

A new series of 2-arylidenehydrazinyl-4-arylthiazole derivatives (2a-k) was designed and synthesized through a rapid, simple, and efficient methodology in excellent isolated yield. These compounds were screened for in vitro antimicrobial activities against eight bacteria, e.g. Bacillus cereus, Staphylococcus aureus, Bacillus subtilis, Bacillus megaterium, Pseudomonas aeruginosa, Shigella dysenteriae, Salmonella typhi, Escherichia coli, and three fungi e.g. Aspergillus oryzae, Candida albicans, and Saccharomyces cerevis. The results indicate that some of the compounds exhibit strong antibacterial activity, depending on the bacterial strain, but show virtually no antifungal activity. The structure-antibacterial activity relationships were studied using some physicochemical and quantum-chemical parameters with the ab initio Hartree-Fock model at the RHF/6-31G level of theory. A good qualitative correlation between predicted lipophilic parameters and antibacterial activity has been found.     

Synthesis and biological evaluation of novel triazole derivatives as antifungal agents

A series of 1-(benzylamino)-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-l-yl)propan-2-ols compounds were synthesized and evaluated for their antifungal activities in vitro.The results showed that compounds 6A and 6B exhibited good antifungal activity.Compound 6A8 showed the strongest antifungal activity,which was significantly higher than that of the lead compounds and positive-control drugs Fluconazole and Itraconazole.In particular,the antifungal activity of compound 6A8 against Candida albicans and Candida krusei(MIC80 both at 0.00097μg/mL) was 515 and 64 times that of Fluconazole,respectively.The structure-activity relationships of the synthesized compounds were discussed,and the docking model of the target compounds with fungal lanosterol 14α-demethylase (CYP51) was analyzed.     

Synthesis and biological evaluation of 12-, 13-, 14-membered macrolides and open chain 2,6-trans-disubstituted dihydropyran analogues for aspergillides

Stereoselective synthesis of twenty (three 12-, five 13- and twelve 14-membered) macrolides and seventeen functionalized 2,6-trans-disubstituted dihydropyran derivatives have been achieved. The key reactions include an Achmatowicz rearrangement, Ferrier-type alkynylation, Yamaguchi macrolactonization and Lindlar’s hydrogenation. Biological screening of the synthesised compounds showed moderate activity against human cancer cell-lines.     

Synthesis and antifungal activity of novel sulfone derivatives containing 1,3,4-oxadiazole moieties

A series of new sulfone compounds containing 1,3,4-oxadiazole moieties were synthesized. The structures of these compounds were confirmed by spectroscopic data (IR, 1H- and 13C-NMR) and elemental analyses. Antifungal tests indicated that all the title compounds exhibited good antifungal activities against eight kinds of plant pathogenic fungi, and some showed superiority over the commercial fungicide hymexazol. Among them, compounds 5d, 5e, 5f, and 5i showed prominent activity against B. cinerea, with determined EC?? values of 5.21 μg/mL, 8.25 μg/mL, 8.03 μg/mL, and 21.00 μg/mL, respectively. The present work demonstrates that sulfone derivatives such as 5d containing a 1,3,4-oxadiazole moiety can be used as possible lead compounds for the development of potential agrochemicals.     

Synthesis,characterization, POM analysis and antifungal activity of novel heterocyclic chalcone derivatives containing acylated pyrazole

Research on Chemical Intermediates - A series of heterocyclic chalcone derivatives (4a–h) were synthesized and characterized by IR, 1H and 13C NMR as well as MS. All the synthesized compounds...     

Synthesis,hypolipidemic and antifungal activity of tetrahydroberberrubine sulfonates

The paper describes the synthesis of new tetrahydroberberrubine derivatives containing polyfl uorophenyl- or alkylsulfonate groups at the O(9) position as well as those containing or not containing a bromine atom at the C(12) position. In a model of acute Triton-induced hyperlipidemia, tetrahydroberberrubine 9-O-(heptafluoro-4’-toluene)sulfonate was shown to reduce the cholesterol level by 23.5%, which is comparable with the eff ect of Simvastatin. At a concentration of 32 μg mL^?1, tetrahydroberberrubine 9-O-pentafluorobenzenesulfonate inhibits the growth of the fungus Cryptococcus neoformans by 81.3±3.5%.