Synthesis of a new class of bis(thiourea)hydrazide pseudopeptides as potential inhibitors of β-sheet aggregation

The modular synthesis of a novel pseudopeptide scaffold based on a bis(thiourea)hydrazide motif is reported. This compound class is designed to display "amphifinity", i.e. association with a peptide strand on one but not the other face of the scaffold, and hence could potentially inhibit β-sheet aggregation.     

Synthesis of β-cyclodextrin dimers as carrier systems for photodynamic therapy of cancer

The aim of our investigation was the development of carrier systems for an application of inert drugs in polyphasic photodynamic tumor therapy. As carrier systems, -cyclodextrin dimers linked at their primary and secondary faces by spacers of varying lengths were synthesized. Cyclodextrins are known to form stable inclusion complexes with porphyrinoïd photosensitizers. The influence of spacer length on the -cyclodextrin dimer inclusion complexes with porphyrinoïd photosensitizers was studied.     

Synthesis of external β-turn templates by reaction of protected dehydroamino acids with cyclic enaminoesters

Two external β-turn templates have been synthesised and one of them has been derivatised as a GLDV-tetrapeptide. In the course of the synthesis an interesting dichotomy was observed in the condensation of exocyclic enamines such as 4 and 19 with protected dehydroamino acids using phosphorus trichloride. When dehydroamido acids were condensed with the enamines 4 and 19 then 6/6 and 6/5 fused bicyclic compounds such as 5 and 20, respectively, were obtained, whereas, when dehydroamino acid urethanes were used, the 5/6 and 5/5 fused products 7 and 23 were obtained. The bicyclic template 20 was converted to the GLDV-tetrapeptide derivative 31 but the sensitivity to base of the acyl-enamine system of the template reduced the yield in the synthesis of the external turn 35.     

Using thioamides to site-specifically interrogate the dynamics of hydrogen bond formation in β-sheet folding

Thioamides are sterically almost identical to their oxoamide counterparts, but they are weaker hydrogen bond acceptors. Therefore, thioamide amino acids are excellent candidates for perturbing the energetics of backbone-backbone H-bonds in proteins and hence should be useful in elucidating protein folding mechanisms in a site-specific manner. Herein, we validate this approach by applying it to probe the dynamic role of interstrand H-bond formation in the folding kinetics of a well-studied β-hairpin, tryptophan zipper. Our results show that reducing the strength of the peptide's backbone-backbone H-bonds, except the one directly next to the β-turn, does not change the folding rate, suggesting that most native interstrand H-bonds in β-hairpins are formed only after the folding transition state.     

Synthesis and characterization of β-cyclodextrin modified hyperbranched carbosilane as stationary phase for GC

A new β-cyclodextrin modified hyperbranched carbosilane stationary phase for gas chromatography was synthesized by substituting the -OH groups ofβ-cyclodextrin with hyperbranched carbosilane and was coated on the inner wall of fused silica capillary column for gas chromatography.The chromatographic behaviors of the stationary phase were studied.The initial testing results showed mat it possessed good separation abilities for several kinds of mixtures,such as benzenes,acrylates,ketones and alkylchlorides.     

Chiral Vinyl Sulfoxides as Useful Reagents for the Synthesis of β-Amino Acid Derivatives

(S)- and (R)-β-amino acid derivatives were synthesized by the asymmetric conjugate addition of ammonia and piperidazine to t-butyl (E)-2-[(R)- and (S)-p-tolylsulfinyl]cinnamates, respectively.     

Highly β-Selective Glycosylation Reactions for the Synthesis of ω-Functionalized Alkyl β-Maltoside as a Co-crystallizing Detergent

Russian Journal of Organic Chemistry - Methods have been reported for the preparation of ω-functionalized alkyl maltoside and glycoside detergents via a simple and inexpensive synthetic route....     

Camphor-based oxazaphospholanes as chiral templates for the enantioselective synthesis of α-chlorophosphonic acids

Constrained camphor-derived oxazaphospholanes have provided an efficient entry for the preparation of enantiomerically enriched α-chlorophosphonic acids.     

Novel Method for the Enantioselective Synthesis of β-Lactams

A novel method for the enantioselective synthesis of β-lactams is described in this study. 2,3-Dihydrobenzooxazin-4-one derived from salicylamide and L-menthone was used as the chiral auxiliary, which reacted with a-bromo-acyl bromides in the presence of pyridine to give carboximides 2. The stereo-controlled Reformatsky-type reactions of carboximides with imines yielded the corresponding trans β-lactams with high enantioselectivities（e.e. 75%-86%） and high chemical yields（63%-85%）, meanwhile, the chiral auxiliary dihydrobenzooxazin-4-one was released and recovered.     

Novel Method for the Enantioselective Synthesis of β-Lactams

A novel method for the enantioselective synthesis of β-lactams is described in this study.2,3-Dihydrobenzooxazin-4-one derived from salicylamide and L-menthone was used as the chiral auxiliary, which reacted with α-bromo-acyl bromides in the presence of pyridine to give carboximides 2. The stereo-controlled Reformatsky-type reactions of carboximides with imines yielded the corresponding trans β-lactams with high enantioselectivities(e.e. 75%-86%) and high chemical yields(63%-85%), meanwhile, the chiral auxiliary dihydrobenzooxazin-4-one was released and recovered.     

Synthesis of two mono-deoxy β-cyclodextrin derivatives as useful tools for confirming DIBAL-H promoted bis-de-O-methylation mechanism

Diisobutylaluminium hydride(DIBAL-H) promotes secondary rim regioselective bis-de-O-methylation of permethylatedβ-cyclodextrin (β-CD) to give diol 2.To gain an insight into the mechanism of this remarkable regioselective behavior,two corresponding permethylatedβ-CDs with an alcohol function at either 2- or 3-position were synthesized in our previous study.As a step further to this work,the two compounds were subjected to deoxygenation reaction with tributyltin hydride in the present of 2,2’- azobisisobutyronitrile affording the corresponding 2- and 3-deoxy permethylatedβ-CD derivatives(19 and 16).The structures of these two compounds were characterized by ID and 2D NMR and HRMS.Compounds 16 and 19 were unable to react with DIBALH which suggests that O-2~A and O-3~B are necessary for DIBAL-H promoted bis-de-O-methylation reaction of permethylatedβ-CD.     

Combination self-assembly of β-sheet peptides and carbon nanotubes: functionalizing carbon nanotubes with bioactive β-sheet block copolypeptides

Understanding the self-assembly behavior of β-sheet peptides is important, not only in constructing bioactive peptide nanostructures, but also in inhibiting uncontrollable protein aggregation in protein-misfolding diseases. Here, the first systematic investigation of combination self-assembly between β-sheet block copolypeptides and CNTs is presented, demonstrating the presence of several different association modes during the combination self-assembly process. Bioactive β-sheet block copolypeptides can self-assemble by themselves, or can be used to functionalize CNT hybrids depending on the situation. This behavior may be important both for fabricating bioactive peptide/CNT hybrids and for controlling/inhibiting protein-misfolding diseases.     

Synthesis and complex formation ability of monomeric and dimeric amphiphilic β-cyclodextrin derivatives

Applying 6-O-monotosyl derivative of β-cyclodextrin and hexane-1,6-diamine monomeric and dimeric (bridging) amphiphilic compounds were obtained, and the opportunity was demonstrated of the preparation on their basis of inclusion compounds at the interaction with 2-(4-isobutylphenyl)propionic acid (Ibuprofen).     

Pyrrole-Protected β-Aminoalkylzinc Reagents for the Enantioselective Synthesis of Amino-Derivatives

Chiral β-aminoalkylzinc halides were prepared starting from optically pure commercial β-amino-alcohols. These amino-alcohols were converted to the corresponding N-pyrrolyl-protected alkyl iodides which undergo a zinc insertion in the presence of LiCl (THF, 25 °C, 10–90 min). Subsequent Negishi cross-coupling or acylation reactions with acid chlorides produced amino-derivatives with retention of chirality. Diastereoselective CBS-reductions of some prepared N-pyrrolyl-ketones provided 1,3-subsituted N-pyrrolyl-alcohols with high diastereoselectivity. Additionally, a deprotection procedure involving an ozonolysis allowed the conversion of the pyrrole-ring into a formamide without loss of optical purity.     

Synthesis of β-Stannyl Esters

A synthesis of β-stannyl esters from ester enolates and iodomethyl (tri-n-butyl) stannane (3) is described.     

Synthesis of Unsymmetrical β-Arylaminoketones

Azomethines derived from aniline were condensed with acetophenone derivatives to obtain new unsymmetrical -arylaminoketones.     

New Synthesis of β-Iodostyrenes

A general procedure for the synthesis of -iodostyrenes is proposed. Aromatic aldehyde and ketone hydrazones are converted into the corresponding -iodostyrenes by treatment with CHI₃ in the presence of a catalytic amount of CuCl.