Studies on Semisynthesis and Anibacterial Activity of 7 β-(5-Methyl-1-Aryl-1H-1,2,3-Triazoly-4-Carboxamido) Cephalosporins

Nine new derivatives of 7 β - (5- methyl- 1- aryl- 1H-1, 2, 3- triazoly- 4- carboxamido) cephalosporins were synthesized by acylction of 7 β -amino group of 7-ACA, 7-ADCA and 7-ACT with 5 -methsyl- 1 -aryl- 1 H- 1,2,3-triazoly-4-formyl chloride. The structure of the compounds were confirmed by elementray analysis IR, HNMR and FAB-MS. Some of them showed significant antibacterial activity

Facile semisynthesis of histone H3 enables nucleosome probes for investigation of histone H_(3)K79 modifications

Histone H3K79 modifications are essential to regulate chromatin structure and gene transcription,but understanding of the molecular mechanisms is limited.Because H3K79 is at globular domain,short histone peptide cannot mimic H3K79 in chromatin.Instead,reconstituted nucleosome-based chemical tools are ideally used to investigate H3K79 modifications.In consequence,H3K79-modified histone H3 with additional chemical handles are required,but such synthesis is challenging and laborious.Here we report a facile semisynthesis method that enables multifunctional histone H3 readily available.H3K79-containing fragment is short for straight peptide synthesis that was later ligated to recombinant expressed H3 fragments for full-length product in large scale.As a result,nucleosomes with H3K79 modifications as well as photo-reactive group and affinity tag were obtained to investigate potential binding proteins.We believe this method that enhances synthetic accessibility of nucleosome probes will accelerate understanding of the underexplored H3K79 modifications.

Semisynthesis and Cytotoxicity Evaluation of a Series of Ocotillol Type Saponins and Aglycones from 20（S）-Ginsenoside Rg2, Rhl, Protopanaxatriol and Their 20（R）-Epimers

Abstract With the oxidation treatment, eighteen compounds were separated from 20（S）-ginsenoside Rg2, Rhl, pro- topanaxatriol（PPT） and their 20（R）-epimers in total and cytotoxicity of most of them was evaluated against three hu- man cancer cell lines HeLa, A549 and MCF-7 by 3-（4,5-dimetylthiazol-z-yl）-2,5-diphenyltetrazolium bromide（MTT） assay. Their structures were confirmed by means of nuclear magnetic resonance（NMR） and mass spectrometry and the results were compared with those of previous literature. In this study, we systematically semisynthesized all four ocotillol type saponins, i.e., （20S, 24S＇）, （20S, 24R）, （20R, 24S） and （20R, 24R）. All the configurations at C20 kept the same with their starting materials. Meanwhile a pair of C24 epimers was generated in terms of ocotillol type saponins In addition, seven compounds（4--8, 13 and 14） were reported firstly. The cytotoxic results distinguished the ocotillol type products（6, 7, 13 and 14） from 20（R）-PPT and 20（R）-ginsenoside Rhl, which possessed better cytotoxicities than their correspondents from 20（S）-epimers against HeLa cells, and the carbonyl group at C3 can improve the cytotoxi- city, which helped us to gain deeper insight into Ocotillol type saponins.

Two New Taxane Diterpenoids from Taxus Chinensis

Two new taxane diterpenoids, 2-deacetoxy-7,9-dideacetyltaxinine J (1) and 2-deacetoxytaxinine B (3), were isolated from the barks of Taxus chinensis. Their structures were elucidated by spectroscopic methods.

Structure modification,antialgal,antiplasmodial,and toxic evaluations of a series of new marine-derived 14-membered resorcylic acid lactone derivatives

Marine natural products play critical roles in the chemical defense of many marine organisms and are essential,reputable sources of successful drug leads.Sixty-seven 14-membered resorcylic acid lactone derivatives 3–27 and 30–71 of the natural product zeaenol(1)isolated from the marine-derived fungus Cochliobolus lunatus were semisynthesized by chlorination,acylation,esterification,and acetalization in one to three steps.The structures of these new derivatives were established by HRESIMS and NMR techniques.All the compounds(1–71)were evaluated for their antialgal and antiplasmodial activities.Among them,14 compounds displayed antifouling activities against adhesion of the fouling diatoms.In particular,9 and 34 exhibited strong and selective inhibitory effects against the diatoms Navicula laevissima and Navicula exigua(EC50=6.67 and 8.55μmol/L),respectively,which were similar in efficacy to those of the positive control SeaNine 211(EC50=2.90 and 9.74μmol/L).More importantly,38,39,and 69–71 showed potent antiplasmodial activities against Plasmodium falciparum with IC50 values ranging from 3.54 to 9.72μmol/L.Very interestingly,the five antiplasmodial derivatives displayed non-toxicity in the cytotoxicity assays and the zebrafish embryos model,thus,representing potential promising antiplasmodial drug agents.The preliminary structure–activity relationships indicated that biphenyl substituent at C-2,acetonide at positions C-5′and C-6′,and tri-or tetra-substituted of acyl groups increased the antiplasmodial activity.Therefore,combining evaluation of chemical ecology with pharmacological models will be implemented as a systematic strategy,not only for environmentally friendly antifoulants but also for structurally novel drugs.

Synthesis of Clionastatins A and B through Enhancement of Chlorination and Oxidation Levels of Testosterone

A full account of semisyntheses of polychlorinated marine steroids clionastatins A and B is described.We have developed a unique two-stage chlorination-oxidation strategy that enabled concise and divergent semisyntheses of clionastatins A and B in 16 steps from inexpensive testosterone.Key transformations in chlorination stage include(a)conformationally controlled,stereospecific dichlorination through an unusualβ-chloronium intermediate to install the diequatorial C1,C2-dichloride;(b)C4-OH directed C19–H oxygenation followed by challenging neopentyl chlorination to install the C19–Cl.The high oxidation level was constructed through(a)the desaturation at C6–C7 through one-pot photochemical dibromination–reductive debromination;(b)regioselective anti-Markovnikov oxidation of the C6–C7 double bond by photoredox-metal dual catalysis to forge the B ring enone;(c)late-stage desaturation with SeO_(2)to introduce C8–C9 double bond.Wharton transposition was used to forge the D-ring enone,and thermodynamically driven epimerization secured the cis-fused C/D ring system.Furthermore,we also provided a 14-step approach to clionastatin A by optimizing the construction of the D-ring enone with a dehydration-oxidation sequence.