Oligomers of β2- and of β3-Homoproline: What are the Secondary Structures of β-Peptides Lacking H-Bonds?

To study the role of H-bonds in stabilizing β-peptidic secondary structures, we have synthesized β-oligopeptides (up to the octadecamer 12 ) consisting of β²- and β³-homoproline, i.e., β-peptides lacking amide protons. The enantiomer purity of the building block β²-homoproline (nipecotic acid, 4 ) was determined by HPLC analysis of the N-(2,4-dinitrophenyl) derivative 5 on a Chiralcel-OD column (cf. Fig. 2). The CD spectra of the all-(S)-β²- and all-(S)-β³-HPro-containing β-peptides display novel and intensive CD patterns which may be indicative of a secondary structure (cf. Fig. 3). It is noteworthy that a distinct CD pattern was observed with the β³-HPro derivatives containing as few as three residues ( 7a ). The crystal structure of a N-deprotected β³-HPro-tripeptide 7c is presented (cf. Figs. 4 and 5), and a model for the structure of β-peptides consisting of β³-HPro is discussed (cf. Figs. 6 and 7).     

Temperature-Dependent NMR and CD Spectra of β-Peptides: On the Thermal Stability of β-Peptide Helices – Is the Folding Process of β-Peptides Non-cooperative?

Temperature-dependent NMR and CD spectra of methanol solutions of a β-hexapeptide and of a β-heptapeptide at temperatures between 298 and 393 K are reported. They establish the fact that the 3₁₄-helical secondary structures of the two β-peptides, 1 and 2 , do not `melt' in the temperature range investigated. This is in sharp contrast to the behavior of the helices of α-peptides and proteins which undergo cooperative unfolding (`denaturing') upon heating. A non-cooperative mechanism is proposed, with a stepwise, rather than an `un-zipping' opening of H-bonded rings (cf. Fig. 6). The experimental results are regarded as evidence that, of the three effects which have been identified as contributing to the stability of β-peptide helices, i.e., H-bonding, hydrophobic interactions, and ethane staggering, the latter one is predominant.     

Note: Helix or No Helix of β‐Peptides Containing β3hAla(αF) Residues?

A remote ⁴J(F,H) coupling (F? C(α)? C(O)? N? H) of up to 4.2 Hz in α‐fluoro amides with antiperiplanar arrangement of the C? F and the C?O bonds (dihedral angle F? C? C?O ca. 180°) confirms that previous NMR determinations, using the XPLOR‐NIH procedure, of the secondary structures of β‐peptides containing β³hAla(αF) and β³hAla(αF₂) residues were correct. In contrast, molecular‐dynamics (MD) simulations, using the GROMOS program with the 45A3 force field, led to an incorrect conclusion about the relative stability of secondary structures of these β‐peptides. The problems encountered in NMR analyses and computations of the structures of backbone‐F‐substituted peptides are briefly discussed.     

Conformationally Biased Mimics of Mannopyranosylamines: Inhibitors of β‐Mannosidases?

The enol ether 7 was prepared by cleavage of the N−O bond of the known isoxazolidine 3 , followed by N‐alkylation to 4 , silylation and oxidation to the N‐oxide 6 , and Cope elimination. Cu‐Catalysed cyclopropanation of 7 led to the diastereoisomeric cyclopropanes 8 and 9 , which were subjected to a Curtius degradation. The resulting carbamates 12 and 16 were deprotected to the ammonium salts 14 and 18 , respectively. Both salts adopt a B_1,4 conformation, similarly as the ester 8 , while the isomeric ester 9 exists in a ca. 6 : 4 equilibrium of the ⁴C₁ and B_1,4 conformers. The β‐mannoside mimic 14 does not inhibit snail β‐mannosidase at 10 mM , but the α‐mannoside mimic 18 inhibits Jack bean α‐mannosidase (IC₅₀=80 μM ). These results are in keeping with the postulate that glycoside cleavage of β‐D ‐glycopyranosides requires a conformational change in agreement with the principle of stereoelectronic control.     

Rhodium‐catalyzed coupling reactions of β‐ or α,β‐substituted vinylpyridines with alkenes via C?H bond activation

β‐ or α,β‐Substituted vinylpyridines react with 3,3‐dimethylbut‐1‐ene in the presence of Wilkinson catalyst [RhCl(PPh₃)₃] to give the corresponding alkylated products along with unusually isomerized products. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:346–350, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10045     

Redox‐Triggered C?C Coupling of Diols and Alkynes: Synthesis of β,γ‐Unsaturated α‐Hydroxyketones and Furans by Ruthenium‐Catalyzed Hydrohydroxyalkylation

Direct ruthenium‐catalyzed C C coupling of alkynes and vicinal diols to form β,γ‐unsaturated ketones occurs with complete levels of regioselectivity and good to complete control over the alkene geometry. Exposure of the reaction products to substoichiometric quantities of p‐toluenesulfonic acid induces cyclodehydration to form tetrasubstituted furans. These alkyne‐diol hydrohydroxyalkylations contribute to a growing body of merged redox‐construction events that bypass the use of premetalated reagents and, hence, stoichiometric quantities of metallic by‐products.     

Evidence for [2+2] Photoreaction of α-Methylene-γ-Butyrolactones with Thymine: An Explanation for Chronic Actinic Dermatitis to Sesquiterpene Lactones?

The photoreactivity of isoalantolactone, a natural sesquiterpene lactone, toward thymine was studied. After 313 nm irradiation of a deoxygenated acetone solution of isoalantolactone (2 x 10(-3) M) and thymine (4 x 10(-3) M), two intermolecular [2 + 2] photoadducts, 3 and 4, were isolated with respective yields of 30% and 18%. The structures of these two photoadducts were determined by a combination of NMR experiments. Compound 3 was identified as a cis-syn-exo intermolecular [2 + 2] photoadduct involving the 5,6 double bond of thymine and the exomethylenic double bond of the lactone, while compound 4 was identified as an intermolecular [2 + 2] photoadduct involving the same bonds but with the cis-syn-endo conformation. This high photoreactivity of sesquiterpene lactones toward thymine could be an explanation of the progressive evolution of allergic contact dermatitis toward chronic actinic dermatitis.     

Synthesis of Enantiomerically Pure Isoxazolidine Monomers for the Preparation of β3‐Oligopeptides by Iterative α‐Keto Acid?Hydroxylamine (KAHA) Ligations

A versatile method for the synthesis of enantiomerically pure isoxazolidine monomers for the synthesis of β³‐oligopeptides via α‐keto acid? hydroxylamine (KAHA) ligation is presented. This one‐pot synthetic method utilizes in situ generated nitrones bearing gulose‐derived chiral auxiliaries for the asymmetric 1,3‐dipolar cycloaddition with methyl 2‐methoxyacrylate. The resulting enantiomerically pure isoxazolidine monomers bearing diverse side chains (proteinogenic and non‐proteinogenic) can be synthesized in either configuration (like‐ and unlike‐configured). The scalable and enantioselective synthesis of the isoxazolidine monomers enables the use of the synthesis of β³‐oligopeptides via iterative α‐keto acid? hydroxylamine (KAHA) ligation.     

CD Spectra in Methanol of β‐Oligopeptides Consisting of β‐Amino Acids with Functionalized Side Chains,with Alternating Configuration,and with Geminal Backbone Substituents – Fingerprints of New Secondary Structures?

β‐Hexa‐, β‐hepta‐, and β‐nonapeptides, 1 – 6 , which carry functionalized side chains (CO₂R, CO, (CH₂)₄NH, CH₂−CH=CH₂) consisting of β³‐amino‐acid residues of alternating configuration, or which carry geminal substituents in the 2‐ or 3‐positions of all residues, have been synthesized (Schemes 1 – 3), and their CD spectra in MeOH are reported (Figs. 2 – 6). Strong Cotton effects (Θ>10⁵) are indicative of the presence of chiral secondary structures. It is suggested by simple modelling (Fig. 1) that the new β‐peptides should not be able to fold to the familiar 3₁₄‐helical structures. Still, three of them ( 3 , 4 , and 5 ) give rise to CD spectra matching those of β‐peptides that are known to be present as (M)‐ or (P)‐3₁₄‐helices in MeOH solution. While possible folding motifs (Figs. 3,b, and 7) of the new β‐peptides have been identified in crystal structures, an interpretation of the CD spectra has to be postponed until NMR solution structures become available. A list of all β‐peptides giving rise to CD spectra with a minimum near 215 nm is included (Table).     

Large‐scale molecular dynamics simulations of HLA‐A*0201 complexed with a tumor‐specific antigenic peptide: Can the α3 and β2m domains be neglected?

Large-scale massively parallel molecular dynamics (MD) simulations of the human class I major histocompatibility complex (MHC) protein HLA-A*0201 bound to a decameric tumor-specific antigenic peptide GVYDGREHTV were performed using a scalable MD code on high-performance computing platforms. Such computational capabilities put us in reach of simulations of various scales and complexities. The supercomputing resources available for this study allow us to compare directly differences in the behavior of very large molecular models; in this case, the entire extracellular portion of the peptide-MHC complex vs. the isolated peptide binding domain. Comparison of the results from the partial and the whole system simulations indicates that the peptide is less tightly bound in the partial system than in the whole system. From a detailed study of conformations, solvent-accessible surface area, the nature of the water network structure, and the binding energies, we conclude that, when considering the conformation of the alpha1-alpha2 domain, the alpha3 and beta2m domains cannot be neglected.     

Enantioselective Palladium‐Catalyzed Insertion of α‐Aryl‐α‐diazoacetates into the O?H Bonds of Phenols

A palladium‐catalyzed asymmetric O H insertion reaction was developed. Palladium complexes with chiral spiro bisoxazoline ligands promoted the insertion of α‐aryl‐α‐diazoacetates into the O H bond of phenols with high yield and excellent enantioselectivity under mild reaction conditions. This palladium‐catalyzed asymmetric O H insertion reaction provided an efficient and highly enantioselective method for the preparation of synthetically useful optically active α‐aryl‐α‐aryloxyacetates.     

Hydrothermal synthesis and thermodynamic properties of 2ZnO · 3B2O3 · 3H2O

The important zinc borate of 2ZnO · 3B₂O₃ · 3H₂O has been synthesized and characterized by means of chemical analysis, XRD, FT-IR, and DTA–TG techniques. The molar enthalpies of solution of H₃BO₃(s) in HCl · 54.561H₂O, of ZnO(s) in the mixture of HCl · 54.561H₂O and calculated amount of H₃BO₃, and of 2ZnO · 3B₂O₃ · 3H₂O(s) in HCl · 54.604H₂O were measured, respectively. With the use of the standard molar enthalpies of formation for ZnO(s), H₃BO₃(s), and H₂O(l), the standard molar enthalpy of formation of ?(5561.7 ± 4.9) kJ · mol^?1 for 2ZnO · 3B₂O₃ · 3H₂O(s) was obtained. Thermodynamic properties of this compound were also calculated by a group contribution method.     

γ-Fe2O3纳米纤维的丙酮敏感特性

采用静电纺丝法制备了PVP/FeC₆H₅O₇复合纳米纤维, 并将复合纤维在500 ℃高温烧结3 h, X射线衍射分析(XRD)表明, 烧结后的产物为正尖晶石结构的γ-Fe₂O₃晶体. 扫描电子显微镜(SEM)观测结果表明, 制得了直径均匀、 连续的复合纳米纤维, 其平均直径约为1000 nm; 烧结后的γ-Fe₂O₃纳米纤维保持了其连续性, 但纤维发生了收缩, 直径较烧结前小, 平均约为600 nm. 比表面积分析表明, γ-Fe₂O₃纳米纤维比表面积为57.18 m²/g. 气敏性能测试结果表明, 230 ℃为γ-Fe₂O₃纳米纤维检测丙酮气体的最佳工作温度. 在此温度下, γ-Fe₂O₃纳米纤维对丙酮气体表现出高响应度[S=6.9, c(Acetone)=7.88×10⁴ mg/m³]和线性度(7.88×10²~1.58×10⁵ mg/m³浓度范围内). 同时, γ-Fe₂O₃纳米纤维气体传感器件还表现出良好的长期稳定性.