General inverse solid-phase synthesis method for C-terminally modified peptide mimetics

Peptide mimetics are of considerable interest as bioactive agents and drugs. C-terminally modified peptide mimetics are of particular interest given the synthetic versatility of the carboxyl group and its derivatives. A general approach to C-terminally modified peptide mimetics, based on a urethane attachment strategy and amino acid t-butyl ester-based N-to-C peptide synthesis, is described. This approach is compatible with the reaction conditions generally employed for solution-phase peptide mimetic synthesis. To develop and demonstrate this approach, it was employed for the solid-phase synthesis of peptide trifluoromethyl ketones, peptide boronic acids, and peptide hydroxamic acids. The development of a versatile general approach to C-terminally modified peptides using readily available starting materials provides a basis for the combinatorial and parallel solid-phase synthesis of these peptide mimetic classes for bioactive agent screening and also provides a basis for the further development of solid-phase C-terminal functional group elaboration strategies.     

DABCO-promoted facile and convenient synthesis of novel isoxazolyl-1H-2,3-pyrrole dicarboxylates

Synthesis of isoxazolyl-1H-2,3-pyrrole dicarboxylate(4) was simply achieved by one-pot three component reaction of isoxazole amine(1) with diethyl acetylenedicarboxylate(DEAD)(2),and glyoxal (3),in acetonitrile catalyzed by diazabicyclo octane(DABCO).     

hNCOcanH pulse sequence and a robust protocol for rapid and unambiguous assignment of backbone (1HN, 15N and 13C′) resonances in 15 N/13C‐labeled proteins

A three‐dimensional nuclear magnetic resonance (NMR) pulse sequence named as hNCOcanH has been described to aid rapid sequential assignment of backbone resonances in ¹⁵N/¹³C‐labeled proteins. The experiment has been derived by a simple modification of the previously described HN(C)N pulse sequence [Panchal et al., J. Biomol. NMR 20 (2001) 135–147]; t₂ evolution is used to frequency label ¹³C′ rather than ¹⁵N (similar trick has also been used in the design of hNCAnH pulse sequence from hNcaNH [Frueh et al., JACS, 131 (2009) 12880–12881]). The modification results in a spectrum equivalent to HNCO, but in addition to inter‐residue correlation peaks (i.e. H_i, C_i?1), the spectrum also contains additional intra‐residue correlation peaks (i.e. H_i?1, C_i?1) in the direct proton dimension which has maximum resolution. This is the main strength of the experiment and thus, even a small difference in amide ¹H chemical shifts (5–6 Hz) can be used for establishing a sequential connectivity. This experiment in combination with the HNN experiment described previously [Panchal et al., J. Biomol. NMR 20 (2001) 135–147] leads to a more robust assignment protocol for backbone resonances (¹H^N, ¹⁵N) than could be derived from the combination of HNN and HN(C)N experiments [Bhavesh et al., Biochemistry, 40 (2001) 14727–14735]. Further, this new protocol enables assignment of ¹³C′ resonances as well. We believe that the experiment and the protocol presented here will be of immense value for structural—and functional—proteomics research by NMR. Performance of this experiment has been demonstrated using ¹³C/¹⁵N labeled ubiquitin. Copyright © 2011 John Wiley & Sons, Ltd.     

Iodine mediated synthesis of some new imidazo[1,2-a]pyridine derivatives and evaluation of their antimicrobial activity

Herein, we reported a series of new 2-(5-methyl-1-aryl-1H-1,2,3-triazol-4-yl)imidazo[1,2-a]pyridines by using iodine and NH₄OAc in good yields. The structures of the titled compounds were characterized by the elemental analysis, ¹H NMR, ¹³C NMR, IR, and mass spectral analysis. All the titled compounds were screened for their in vitro antibacterial and antifungal activities by using streptomycin and Nystatin as standard drugs. The compounds 3k , 3l , 3g , and 3c exhibited potent activity against the tested bacterial strains and 3k , 3l , and 3c exhibited potent activity against the tested fungal strains than the reference drugs.     

Ultrasound‐Assisted Pechmann Condensation of Phenols With β‐Ketoesters to Form Coumarins,in the Presence of Bismuth(III) Chloride Catalyst

Ultrasound was found to synergistically accelerate the condensation of phenol with β‐ketoesters in the presence of BiCl₃. In the absence of ultrasound, under the same conditions, the reaction was found to be slow. Thus, the reaction can be carried out in the presence of ultrasound at room temperature (28–30°C), with a considerable reduction of reaction time, with high yield and high purity of coumarins.     

Concise Total Synthesis of (−)-Erinapyrone B from D-(+)-Malic Acid

A convenient and facile enantioselective synthesis of (?)-erinapyrone B from commercially available D-(+)-malic acid has been achieved in seven steps. One of the key steps in this synthesis was the one-pot reaction of palladium(II)-mediated Wacker-type oxidative cyclization in the presence of a catalytic amount of p-toluenesulphonic acid (p-TsOH) which has been found to be effective for the preparation of enantiopure 2,3-dihydro-4H-pyran-4-one from the corresponding enantiopure β-hydroxyenone via enantio-enriched diketohydroxy intermediate.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Dependence of surface enhanced Raman scattering on the plasmonic template periodicity

Surface enhanced Raman scattering has been investigated from rhodamine 6G molecules embedded in polymethyl methacrylate (R6G+PMMA) and coated on one-dimensional and two-dimensional gold-dielectric gratings fabricated by laser interference lithographically. The Raman signals from these plasmonic templates are 200 to 400 times larger than the signal from R6G+PMMA coated on plain gold films. The enhancement of the Raman signal varies almost periodically with the period of the grating. Finite-difference time-domain simulations show that large electromagnetic near fields occur at the metallic edges due to the resonant excitation of localized surface plasmon of the gold patches by the pump laser. These give rise to large enhancements of the Raman signal. The dependence on period is due to the combined effects of the localized surface plasmon and the periodic grating that couples the pump laser to the surface plasmon polariton.