Unprecedented Chain‐Length‐Dependent Conformational Conversion Between 11/9 and 18/16 Helix in α/β‐Hybrid Peptides

α,β‐Hybrid oligomers of varying lengths with alternating proteogenic α‐amino acid and the rigid β^2,3,3‐trisubstituted bicyclic amino acid ABOC residues were studied using both X‐ray crystal and NMR solution structures. While only an 11/9 helix was obtained in the solid state regardless of the length of the oligomers, conformational polymorphism as a chain‐length‐dependent phenomenon was observed in solution. Consistent with DFT calculations, we established that short oligomers adopted an 11/9 helix, whereas an 18/16 helix was favored for longer oligomers in solution. A rapid interconversion between the 11/9 helix and the 18/16 helix occurred for oligomers of intermediate length.     

Synthesis of β‐Haloketones by β‐Addition Reactions of α,β‐Unsaturated Ketones with BX3 (X = Br,Cl) as Halide Source

A series of β‐bromoketones and β‐chloroketones were synthesized by the addition reactions of α,β‐unsaturated ketones under BX₃ (X = Br, Cl) and ethylene glycol reaction system. The α,β‐unsaturated ester also was successfully converted to its corresponding β‐bromoester under the reaction condition.     

A Mild Isomerization Reaction for β,γ‐Unsaturated Ketone to α,β‐Unsaturated Ketone

A series of β,γ‐unsaturated ketones were isomerized to their corresponding α,β‐unsaturated ketones by the introduction of DABCO in iPrOH at room temperature. The endo‐cyclic double bond (β,γ‐position) on ketone was rearranged to exo‐cyclic double bond (α,β‐position) under the reaction conditions.     

Studies on the Mass Spectra of N‐Aryl α,β‐Unsaturated γ‐Lactams

The mass spectra of a series of N‐aryl α,β‐unsaturated γ‐lactams were studied. Besides the molecular ion, the three characteristic fragments such as [M⁺‐29], [M⁺‐55], and [M⁺‐82] were commonly found in a series of N‐Aryl α,β‐unsaturated γ‐lactams in EI/MS. Further more the mechanism for the interpretation of these fragments is also de scribed.     

Synthesis of new optically active α,α′,β‐trisubstituted‐β‐lactones as monomers for stereoregular biopolyesters

Various optically active (4R)‐alkyloxycarbonyl‐3,3‐dialkyl‐2‐oxetanones as monomers were synthesized from L‐(S)‐malic acid in six steps to prepare a new family of stereopolyesters for biomedical applications. The synthesis began with an esterification followed of a dialkylation in the aim to introduce hydrophobic groups as methyl or reactive group as allyl. Then, a saponification has permitted to obtain the corresponding diacids that reacted with appropriate alcohols to furnish different monoesters. The last and most important step was activation of hydroxyl group of monoesters with the asymmetric carbon configuration inversion according to the Mitsunobu reaction. Thus, this reaction has provided lactones from monoesters with 100% enantiomeric excess which was confirmed by ¹H NMR and by the synthesis of corresponding isotactic and semicrystalline homopolyesters. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2586–2597     

Photolysis of α,β‐Epoxyketones: A Green Synthesis of β‐Hydroxyenones through Tandem H‐Abstraction,Ring Cleavage and Isomerisation

The photochemical behavior of various substituted epoxycarbonyl compounds consisting of more than one possible photo‐labile site (i.e. δ‐hydrogen, β‐hydrogen and epoxide ring) has been investigated. These compounds on photo‐irradiation produced the β‐hydroxyenones in an eco‐friendly green approach. Mechanistically, these photo‐transformations have been envisaged to occur via an intramolecular β‐hydrogen abstraction by the carbonyl group of benzoyl moiety to generate the 1,3‐biradical followed by epoxide ring opening that isomerizes into the photoproducts. The photolysis of the probed epoxy ketones didn’t furnish any photoproduct through δ‐hydrogen abstraction, whatsoever. This exclusive preference for β‐H abstraction over δ‐H abstraction by carbonyl group has been vindicated by the MM2 energy mini‐ mized program for the investigated photochemical substrates. The structures of these photoproducts were established from the analysis of their spectral parameters (IR, ¹H/¹³C NMR and Mass) and single crystal X‐ray crystallography data.     

Synthesis of Phenanthrene Derivatives through the Reaction of an α,α‐Dicyanoolefin with α,β‐Unsaturated Carbonyl Compounds

Phenanthrene derivatives were prepared by reacting an α,α‐dicyanoolefin with different α,β‐unsaturated carbonyl compounds resulting from Wittig reaction of ninhydrin and phosphanylidene or condensation of barbituric acid and an aldehyde. The easy procedure, mild and metal‐catalyst free, reaction conditions, good yields, and no need for chromatographic purifications are important features of this protocol. The structures of the product of type 3 and 5 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS). A plausible mechanism for this type of reaction is proposed (Scheme 1).     

TBAF‐Mediated Dimerization Reaction of β,γ‐Unsaturated Arylketones

A simple and high‐yield method for the synthesis of several 1,5‐diaryl‐1,5‐dicarbonyl compounds has been established starting from TBAF‐mediated isomerization and dimerization reaction of β,γ‐unsaturated arylketones (allyl arylketones) with mono‐, di‐, and tri‐methoxy groups, which is derived from allylation of commercially available different benzaldehydes and followed by oxidation of the resulting secondary alcohols.     

Microwave‐Assisted Synthesis of β‐Lactams and Cyclo‐β‐dipeptides

Different cyclo‐β‐dipeptides were prepared from corresponding N‐substituted β‐alanine derivatives under mild conditions using PhPOCl₂ as activating agent in benzene and Et₃N as base. To evaluate β³‐substituent influence, the amino acids 7 – 26 were synthesized, and a β‐lactam formation reaction was carried out instead of cyclo‐β‐dipeptide formation. The crystal structures of three derivatives of cyclo‐β‐peptides and one β‐lactam are presented.     

Radical‐initiated polymerization of β‐methyl‐α‐methylene‐γ‐butyrolactone

β‐Methyl‐α‐methylene‐γ‐butyrolactone (MMBL) was synthesized and then was polymerized in an N,N‐dimethylformamide (DMF) solution with 2,2‐azobisisobutyronitrile (AIBN) initiation. The homopolymer of MMBL was soluble in DMF and acetonitrile. MMBL was homopolymerized without competing depolymerization from 50 to 70 °C. The rate of polymerization (R_p) for MMBL followed the kinetic expression R_p = [AIBN]^0.54[MMBL]^1.04. The overall activation energy was calculated to be 86.9 kJ/mol, k_p/k_t^1/2 was equal to 0.050 (where k_p is the rate constant for propagation and k_t is the rate constant for termination), and the rate of initiation was 2.17 × 10^?8 mol L^?1 s^?1. The free energy of activation, the activation enthalpy, and the activation entropy were 106.0, 84.1, and 0.0658 kJ mol^?1, respectively, for homopolymerization. The initiation efficiency was approximately 1. Styrene and MMBL were copolymerized in DMF solutions at 60 °C with AIBN as the initiator. The reactivity ratios (r₁ = 0.22 and r₂ = 0.73) for this copolymerization were calculated with the Kelen–Tudos method. The general reactivity parameter Q and the polarity parameter e for MMBL were calculated to be 1.54 and 0.55, respectively. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 1759–1777, 2003     

Design and Synthesis of α,β‐Epoxyketones as New Anticancer Agents

As epoxy functional group has high anticancer activity, α,β‐epoxyketones were designed and synthesized as new anticancer agents, and their structures were confirmed by UV, ¹H NMR, IR, MS technigeces and elemental analysis. Their in vitro anticancer activities were evaluated by MTT method and the results showed that the compound 4c exhibited good activity with IC₅₀ of 17.8, 22.0 and 24.1 µg/mL against A‐549, Hela and HepG2 cells, respectively. The dose of LD50 of the mice by intragastric administration was 1864.4 mg/kg. Therefore, the α,β‐epoxyketones could potentially provide as new anticancer agents.     

Palladium‐Catalyzed Carbonylative α‐Arylation to β‐Ketonitriles

A carbonylative α‐arylation process employing unactivated nitriles for the first time is described. The reaction tolerates a range of (hetero)aryl iodides and several nitrile coupling partners. No prefunctionalization of the nitriles is necessary and the resulting β‐ketonitriles are obtained in good to excellent yields. The methodology also allows for a convenient ¹³C‐labelling of the generated carbonyl moiety.     

Ligand‐free CuI‐catalyzed coupling and cyclization of β‐bromo‐α,β‐unsaturated amides with formamide leading to pyrimidinones

β‐Bromo‐α,β‐unsaturated amides were coupled and cyclized with formamide in DMF at 100°C in the presence of a catalytic amount of a copper(I) salt along with a base to give the corresponding pyrimidinones in good yields. Copyright © 2013 John Wiley & Sons, Ltd.     

Palladium‐catalyzed carbonylative cyclization of β‐bromo‐α,β‐unsaturated carboxylic acids with primary amines leading to N‐alkylmaleimides

Cyclic β‐bromo‐α,β‐unsaturated carboxylic acids are carbonylatively cyclized with primary amines under carbon monoxide pressure in MeCN in the presence of a catalytic amount of PdCl₂(PPh₃)₂ to give N‐alkylmaleimides. Copyright © 2012 John Wiley & Sons, Ltd.     

Artificial β‐Double Helices from Achiral γ‐Peptides

Double helices are not common in polypeptides and proteins except in the peptide antibiotic gramicidin A and analogous l,d ‐peptides. In contrast to natural polypeptides, remarkable β‐double‐helical structures from achiral γ‐peptides built from α,β‐unsaturated γ‐amino acids have been observed. The crystal structures suggest that they adopted parallel β‐double helical structures and these structures are stabilized by the interstrand backbone amide H‐bonds. Furthermore, both NMR spectroscopy and fluorescence studies support the existence of double‐helical conformations in solution. Although a variety of folded architectures featuring distinct H‐bonds have been discovered from the β‐ and γ‐peptide foldamers, this is the first report to show that achiral γ‐peptides can spontaneously intertwine into β‐double helical structures.     

Chiral separation of cathinone derivatives using β‐cyclodextrin‐assisted capillary electrophoresis–Comparison of four different β‐cyclodextrin derivatives used as chiral selectors

In the past decade, more than 100 different cathinone derivatives slopped over entire Europe due to their enormous popularity. Generally, these novel psychoactive substances are easily available via the internet. This fact leads to various social problems, since cathinones are substances with consciousness‐changing effects and are mainly misused for recreational matters by their consumers. Cathinones possess a chiral center including two enantiomeric forms with potentially different pharmacological behavior. This fact makes analytical method development regarding their chiral separation indispensable. In this study, a chiral capillary zone electrophoresis method for the enantioseparation of 61 cathinone and pyrovalerone derivatives was developed by means of four different β‐cyclodextrin derivatives. As chiral selectors, native β‐cyclodextrin as well as three of its derivatives namely acetyl‐β‐cyclodextrin, 2‐hydroxypropyl‐β‐cyclodextrin, and carboxymethyl‐β‐cyclodextrin were used. The cathinone and pyrovalerone derivatives were either purchased in internet stores or seized by police. As a result, overall 58 of 61 studied substances were partially or baseline separated by at least one of the four chiral selectors using 10 mM of β‐cyclodextrin derivative in a 10 mM sodium phosphate buffer (pH 2.5). Furthermore, the method was found to be suitable for simultaneous enantioseparations, for enantiomeric purity checks and to differentiate between positional isomers. Moreover, an intra‐ and an interday validation was performed successfully for each chiral selector to prove the robustness of the method.