A novel strategy for oligopeptide synthesis using a polymer-supported ammonium fluoride

A novel method for the preparation of oligopeptides with a PS-ammonium fluoride in the solution phase is reported. The synthesis of lipid II pentapeptide is efficiently synthesized via a PS-ammonium fluoride without chromatographic purifications. The method reported here is very convenient to synthesize a relatively large amount of oligopeptides with abundantly available Fmoc-protected amino acids in a time efficient manner.     

A novel method for the synthesis of dinucleoside boranophosphates by a boranophosphotriester method

2'-Deoxyribonucleoside-3'-boranophosphates (nucleotide monomers), including four kinds of nucleobases, were synthesized in good yields by the use of new boranophosphorylating reagents. We have explored various kinds of condensing reagents as well as nucleophilic catalysts for the boranophosphorylation reaction with nucleosides. In the synthesis of dinucleoside boranophosphates, undesirable side reactions occurred at the O-4 of thymine and the O-6 of N2-phenylacetylguanine bases. To avoid these side reactions, additional protecting groups, benzoyl (Bz) and diphenylcarbamoyl (Dpc) groups, were introduced to thymine and guanine bases, respectively. As a result, the condensation reactions proceeded smoothly without any side reactions, and the dimers including four kinds of nucleobases were obtained in excellent yields. In the deprotection of the 5'-DMTr group, Et3SiH was found to be effective as a scavenger for the DMTr cation which caused a P-B bond cleavage. After removal of the other protecting groups by the conventional procedure, four kinds of dinucleoside boranophosphates were obtained in good yields.     

Design, synthesis and biological evaluation of novel glucokinase activators

A new series of benzamide derivatives as glucokinase activators(GKAs) were designed and synthesized,and their activation for glucokinase were evaluated by the preliminary glucokinase activity assay.The structure-activity relationship(SAR) is discussed. The result shows that compound 12d and 12h have potent activity reference drug RO-28-1675.     

Stereoselective synthesis of (Z)-2-fluoro-1-alkenyl(phenyl)iodonium tetrafluoroborates

[reaction: see text] (Z)-2-Fluoro-1-alkenyl(phenyl)iodonium salts were stereoselectively prepared by the reaction of alkynyl(phenyl)iodonium salts with aqueous HF in good yields. The method is applicable to the synthesis of fluoroalkenyliodonium salts having functional groups such as ketone, ester, and chloride. (Z)-2-Fluoro-1-alkene, (Z)-2-fluoro-2-alkenoate, and (Z)-beta-fluoroenyne could be stereoselectively prepared from the fluoroalkenyliodonium salt.     

Organoboron compounds,synthesis of allyl(dialkyl)boranes and diallyl(alkyl)boranes

Highly reactive allyl(dialkyl)-, crotyl(dialkyl)-, 3,3-dimethylallyl(dialkyl)-(= prenyl(dialkyl), and diallyl(alkyl)-boranes were prepared by allylation of esters R₂BOR′, RB(OR′)₂ or thioesters R₂BSR′ (R = alkyl) using allylic derivatives of aluminium, magnesium or boron in exchange reactions.The titled compounds are stable up to 100°C and do not symmetrize even on heating at 100°C for a long time. PMR spectroscopy data show that the characteristic feature of these compounds is a permanent allyl rearrangement, the rate of which increases with an increase in temperature. For allyl(diethyl)-borane at 100°C and 125°C the rates are equal to 2500 and 5000 sec^?1 respectively; activation energy of the rearrangement amounts to 11.8±0.2 kcal mol^?1.The boronallyl bonds in unsymmetrical allyl(alkyl)boranes readily split under the action of water and alcohols, protonolysis being accompanied by allyl rearrangement, crotyl and prenyl compounds are converted into 1-butene or 3-methyl-1-butene, respectively.     

Design, synthesis, and evaluation of a novel class of enantioselective electrophilic fluorinating agents: N-fluoro ammonium salts of cinchona alkaloids (F-CA-BF(4))

The first enantiopure N-fluoro quaternary ammonium salts of cinchona alkaloids as enantioselective fluorinating agents are reported. A one-step transfer-fluorination on the naturally occurring cinchona alkaloids gave the fluorinating agents F-CA-BF(4). This new generation of fluorinating agents exhibited asymmetric induction up to 61% on fluorination of enolates and silyl enol ethers of 2-methyl-1-tetralone.     

Reactions of N,N-(dialkyl)arylthioacetamides with dialkyl acetylenedicarboxylates

2-(Alkoxycarbonylmethylidene)-4-aryl-5-(dialkylamino)thiophen-3(2H)-ones were synthesized by condensation of N,N-(dialkyl)arylthioacetamides with dialkyl acetylenedicarboxylates. Intermediate substituted vinylic sulfides were isolated. When heated or in the presence of an acid or a base, they undergo cyclization into thiophenes.     

A new approach to stereospecific synthesis of P-chiral phosphorothioates. Preparation of diastereomeric dithymidyl-(3'-5') phosphorothioates

A new method for stereospecific synthesis of P-chiral phosphorothioates based on intramolecular nucleophile catalysis was developed.     

An efficient synthesis of dialkyl 2-(diphenoxyphosphoryl)-3-(alkylthio)succinates from alkylthiols, triphenyl phosphite and dialkyl acetylenedicarboxylates

An efficient synthesis of dialkyl 2-(diphenoxyphosphoryl)-3-(alkylthio)succinates, as a mixture of two diastereomers, in 78–90% yields, is described via reaction between alkylthiols, dialkyl acetylenedicarboxylates, and triphenyl phosphite. The structures of products were deduced from their high-field ¹H, ¹³C, and ³¹P NMR spectra, and IR spectral data. Since these hosphonate esters possess two stereogenic centers, two diastereomers with gauche HCCH arrangements are possible. Observation of ³ J _HH = 3.5-4.6 Hz for the vicinal methine protons confirmed the dominance of the gauche arrangement. A mechanism is proposed for the formation of products.     

Asymmetric, catalytic synthesis of alpha-chiral amines using a novel bis(phosphine) monoxide chiral ligand

We have shown that Me-DuPHOS monoxide (BozPHOS) is a very effective ligand in the copper-catalyzed addition of dialkylzinc to N-phosphinoylimines providing access to alpha-chiral amines. The new ligand is particularly effective for the addition of the lesser reactive dimethylzinc. The major advantages of this process are high yields, broad substrate scope, and high enantioselectivities with low catalyst loading (3 mol %).     

Selective hydrothermal synthesis of ammonium vanadates(V) and (IV,V)

Transition Metal Chemistry - The reduction of vanadium pentoxide with formamide under hydrothermal–microwave treatment at 180–210 °C allows for the selective synthesis of...     

An efficient method for the synthesis of dialkyl chlorophosphates from trialkyl phosphites using bis（trichloromethyl） carbonate

A mild and simple method for the synthesis of dialkyl chlorophosphates is described, bis（trichloromethyl） carbonate （BTC） is used as the effective reagent for the conversion of dialkyl phosphites to their corresponding dialkyl chlorophosphates under mild conditions.     

"Fleximers". Design and synthesis of a new class of novel shape-modified nucleosides(1)

A new class of shape-modified nucleosides is introduced. These novel "fleximers" feature the purine ring systems of adenosine, inosine, and guanosine split into their individual imidazole and pyrimidine components (as in 1-3). This structural modification serves to introduce flexibility into the nucleoside while still retaining the elements essential for recognition. As a consequence, these novel fleximers should find use as bioprobes for investigating enzyme-coenzyme binding sites as well as nucleic acid and protein interactions. Their design and synthesis are described.     

The synthesis and biological activity of new 7-[2-(cyanomethyl)piperazinyl]- and 7-[3-(cyanomethyl)piperazinyl]quinolone antibacterials

Some novel 7-[2- or 3-(cyanomethyl)piperazinyl]quinolones have been prepared. Most notable, 2-cyanomethyl-piperazine 5 and 1-methyl-2-cyanomethylpiperazine 8 at the quinolone C-7 position produce products with good in vitro antibacterial activity. The key step in the synthesis of these products involves the regioselective deprotection of the benzyl group in function of the time reaction.     

Formation of isoxazole derivatives via nitrile oxide using ammonium cerium nitrate (CAN): a novel one-pot synthesis of 3-acetyl- and 3-benzoylisoxazole derivatives

The reactions of alkenes and alkynes with ammonium cerium(IV) nitrate ((NH₄)₂Ce(NO₃)₆, CAN(IV)) in acetone under reflux gave the corresponding 3-acetyl-4,5-dihydroisoxazole and 3-acetylisoxazole derivatives. In the case of acetophenone, 3-benzoyl-4,5-dihydroisoxazole and 3-benzoylisoxazole derivatives were obtained. Reaction of acetone with CAN(IV) afforded the corresponding furoxan (3,4-diacetyl-1,2,5-oxadiazole 2-oxide) as the dimer of nitrile oxide. Moreover, it was found that yields of isoxazole derivatives were improved using ammonium cerium(III) nitrate tetrahydrate ((NH₄)₂Ce(NO₃)₅·4H₂O, CAN(III))-formic acid. The reaction mechanisms based on nitration and formation of nitrile oxide mediated by CAN(IV) or CAN(III) from acetone or acetophenone are also proposed.     

Synthesis of dinucleoside,di(2′-deoxy-2′-fluoro)nucleoside phosphates and phosphorothioates and their stability to snake venom phosphodiesterase

Dithymidine, di(2′-deoxy-2′-fluoro)-cytidine and -uridine phosphate and phosphorothioate have been synthesized. The stereochemistry of the condensation reaction between 2′-deoxy-2′-fluoronucleoside phosphoramidite and nucleoside was preliminarily investigated. The diastereomer separation of the protected phosphorothioates was performed by silica gel column chromatography. The stability of these compounds to snake venom phosphodiesterase was determined.     

Thermally stable rare earth dialkyl complexes supported by a novel bis(phosphinimine)pyrrole ligand

A novel bis(phosphinimine)pyrrole based ligand (HL) and its synthesis are reported. Rare earth dialkyl complexes of the ligand, LLn(CH(2)SiMe(3))(2) (Ln = Er, Lu, Sc), have been prepared and found to exhibit high thermal stability in solution. The protio-ligand and dialkyl lanthanide complexes (Ln = Er, Lu) have been characterised by single crystal X-ray diffraction studies.     

Discovery of 2-aminothiazole-4-carboxamides, a novel class of muscarinic M(3) selective antagonists, through solution-phase parallel synthesis

Synthesis and structure-activity relationship of a new class of muscarinic M(3) selective antagonists were described. In the course of searching for a muscarinic M(3) antagonist with a structure distinct from those of the 2-(4,4-difluorocyclopentyl)-2-phenylacetamide derivatives, we identified a thiazole-4-carboxamide derivative (1) as a lead compound in our in-house chemical collection. Since this compound (1) showed relatively low binding affinity (K(i)=140 nM) for M(3) receptors in the human binding assays, we tried to improve its potency and selectivity for M(3) over M(1) and M(2) receptors by derivatization of 1 through a combinatorial approach. A solution-phase parallel synthesis effectively contributed to the optimization of each segment of 1. Thus, we have identified a cyclooctenylmethyl derivative (3e) and a cyclononenylmethyl derivative (3f) as representative M(3) selective antagonists in this class.