S- to N-Acyl transfer in S-acylcysteine isopeptides via 9-, 10-, 12-, and 13-membered cyclic transition states.

S-Acyl cysteine peptides containing α-, ß- or γ-amino acid residues undergo long-range S- to N-acyl transfer to give analogs of native tripeptides and tetrapeptides containing additional carbon atoms in the chain. The ease of intramolecular S → N-acyl transfer relative to intermolecular transacylation is favored increasingly for 9 < 12 < 13 ~ 10-membered cyclic transition states; the observed order is explained on conformational and intermolecular interaction considerations.

Similarity analysis, synthesis, and bioassay of antibacterial cyclic peptidomimetics.

The chemical similarity of antibacterial cyclic peptides and peptidomimetics was studied in order to identify new promising cyclic scaffolds. A large descriptor space coupled with cluster analysis was employed to digitize known antibacterial structures and to gauge the potential of new peptidomimetic macrocycles, which were conveniently synthesized by acylbenzotriazole methodology. Some of the synthesized compounds were tested against an array of microorganisms and showed antibacterial activity against Bordetella bronchistepica, Micrococcus luteus, and Salmonella typhimurium.

Traceless chemical ligations from O-acyl serine sites.

Chemical ligation via O- to N-acyl transfer of O-acylated serine containing peptides affords serine containing native peptides via 8- and 11-membered cyclic transition states opening the door to a wide variety of potential applications to peptide elaboration. The feasibility of these traceless chemical ligations is feasible as supported by computation.

Benzotriazol-1-yl-sulfonyl azide for diazotransfer and preparation of azidoacylbenzotriazoles.

Benzotriazol-1-yl-sulfonyl azide, a new crystalline, stable, and easily available diazotransfer reagent provides N-(α-azidoacyl)benzotriazoles convenient for N-, O-, C- and S-acylations. The efficient syntheses of various amides, azido protected peptides, esters, ketones and thioesters is reported together with a wide range of azides (including α-azido acids from α- amino acids in partially aqueous conditions) and diazo compounds.

Synthesis of amino acid derivatives of quinolone antibiotics.

Optically pure conjugates of quinolone antibiotics with naturally occurring amino acids are synthesized in 40-98% yields.

Dye labelling of nucleosides.

Dye-labelled nucleosides were obtained in 30-79% (average 45%) yields by treating N-(4-arylazobenzoyl)-1H-benzotriazoles 3a-b with appropriate nucleosides. Similarly, 3a-b afforded dye-labelled threoninol conjugates in 55-89% (average 67%) yields. All novel products were characterized by NMR and elemental analysis.

Gelation behavior of 2H-chromene N-acylamino acid conjugates.

2H-Chromene-based conjugates of N-acyl-1,omega-amino acids (5, 9a-f, 14a-f) of natural amino acids (10a,b) and of dipeptide (10c) are prepared (60-97%) by N-acylbenzotriazole methodology in aqueous media at 20 degrees C. Gelation properties of the corresponding sodium salts in DMF and DMSO are generalized with respect to an increase or decrease in the chain length of the spacer.

Syntheses of IAA- and IPA-amino acid conjugates.

Amino acid derivatives of IAA and IPA are prepared conveniently and efficiently by coupling of readily available 2a-b with diverse free amino acids 3a-g and (3c+3c') to give compounds 4a-j, (4c+4c') and (4h+4h') in 38-70% yields. Similarly, 2a-b afforded IAA and IPA peptide conjugates 6a-b in 32-40% yields. Complete retention of chirality was supported by NMR and HPLC analysis.

Synthesis of o-sulfamidotriazobenzenes from 1,1'-sulfonylbis(benzotriazole).

Easily accessible 1,1'-sulfonylbis(benzotriazole) (Bt2SO2, 1) reacts with secondary amines at room temperature to afford (i) the corresponding o-sulfamidotriazobenzenes 2a-d (53-75%) via concurrent substitution of the first and ring opening of the second benzotriazolyl group and (ii) N-sulfonylbenzotriazoles 3b,c,e,f (7-73%). 1-(Morpholine-4-sulfonyl)-1H-benzotriazole 3c reacts with piperidine, pyrolidine, and N-methylpiperazine under microwave irradiation (120 W) at 120 degrees C for 10 min to give the unsymmetrical sulfamides 4a-c (80-90%).

Alkyl, unsaturated, (hetero)aryl, and N-protected alpha-amino ketones by acylation of organometallic reagents.

Stable and easily accessible N-acylbenzotriazoles, derived from a variety of aliphatic, unsaturated, (hetero)aromatic, and N-protected alpha-amino carboxylic acids, were reacted with Grignard and heteroaryllithium reagents to afford corresponding ketones in good to excellent yields.

Photoelectron spectra and electronic structure of some 4-substituted 2-allylanisoles.

The electronic structures of 4-substituted 2-allyl anisoles (1-9) have been investigated by ultraviolet photoelectron spectroscopy and quantum chemical methods. The ionisation potentials corresponding to the pi MOs pi(2) and pi(3) of the phenyl ring, and the n(O) orbital of the methoxy group as well as the allylic pi(C=C) orbital could be determined and assigned for 1-9. Linear regression analyses of the IPs related to these orbitals with different substituent constants indicated that Hammett sigma(p) values performed satisfactorily to fair for pi(2), pi(3) and n(O) but poor for allylic pi(C=C). Other substituent constants such as R and R(-) were fair only for pi(2) and pi(3), but poor for n(O) and pi(C=C).

Spectroscopic and theoretical studies on intramolecular OH-pi hydrogen bonding in 4-substituted 2-allylphenols.

2-Allylphenol (1) constitutes a mixture of conformers, in which an OH-pi hydrogen bonded closed (1a) and open form (1b) can be distinguished. 4-Substituted 2-allyphenols (2-9) have been synthesised and investigated by theoretical and spectroscopic methods. In 1-9, the energy and the structure of the hydrogen bonds show distinct variation with substituents. In the PE spectra of most compounds, two ionisations can be distinguished which are related to the allylic pi(C[double bond]C) orbitals of the two conformers a and b and differ in energy by DeltaIP(C[double bond]C). Alternatively, DeltaIP(C[double bond]C) can be determined indirectly from comparison of the PE spectra of the respective phenols and anisoles with the same substituents. DeltaIP(C[double bond, length as m-dash]C) values between 0.3 and 1.1 eV were found. Frequency shifts Deltanu(OH) of the O-H vibration in CHCl3 solution were measured by IR spectroscopy. By means of correlation analysis of the relationship between the strength of the intramolecular hydrogen bond, DeltaIP(C[double bond]C), Deltanu(OH) values and substituent constants it is established how substituents in 4-position affect the intramolecular OH-pi hydrogen bond. The investigations demonstrate that the DeltaIP(C[double bond]C) data can be used as descriptors for this intramolecular interaction.