Gangavaram V. M. Sharma

sp3 C-H bond activation with ruthenium(II) catalysts and C(3)-alkylation of cyclic amines.

A selective C(3)-alkylation via activation/functionalization of sp(3) C-H bond of saturated cyclic amines was promoted by (arene)ruthenium(II) complexes featuring a bidentate phosphino-sulfonate ligand upon reaction with aldehydes. This highly regioselective sustainable transformation takes place via initial dehydrogenation of cyclic amines and hydrogen autotransfer processes.

Ruthenium(IV) Complexes Featuring P,O‐Chelating Ligands: Regioselective Substitution Directly from Allylic Alcohols

Branching out: A new ruthenium(IV) complex (1), containing a P,O-chelating ligand, is an efficient precatalyst for regioselective allylations starting from various allylic alcohol derivatives.

Synthesis and Structure of α/δ-Hybrid Peptides—Access to Novel Helix Patterns in Foldamers

Stimulated by an overview on all periodic folding patterns of alpha/delta-hybrid peptides with 1:1 alternating backbone provided by ab initio molecular orbital theory, the first representatives of this foldamer class were synthesized connecting novel C-linked carbo-delta-amino acid constituents and L-Ala. In agreement with theoretical predictions, extensive NMR spectroscopic analyses confirm the formation of new motifs of 13/11-mixed helical patterns in these peptides supported by the rigidity of the D-xylose side chain in the selected delta-amino acid constituents. Relationships between possible helix types in alpha/delta-hybrid peptides and their counterparts in other 1:1 hybrid peptide classes and native alpha-peptides are discussed; these indicate the high potential of these foldamers to mimic native peptide secondary structures. The design of alpha/delta-hybrid peptides provides an opportunity to expand the domain of foldamers and allows the introduction of desired functionalities through the alpha-amino acid constituents.

Synthesis of (±)-zearalenone

The aliphatic portion of (±)-zearalenone has been synthesised by a new simple route starting from 2,3-dihydropyran and 2-acetyl-γ-butyrolactone by employing dithiane for C-C bond formation. The final condensation of this segment with the aromatic part and subseqnet transformations led to (±)-zearalenone.

Three-Residue Turns in α/β-Peptides and Their Application in the Design of Tertiary Structures†

A new three-residue turn was serendipitously discovered in alpha/beta hybrid peptides derived from alternating C-linked carbo-beta-amino acids (beta-Caa) and L-Ala residues. The three-residue beta-alpha-beta turn at the C termini, nucleated by a helix at the N termini, resulted in helix-turn (HT) supersecondary structures in these peptides. The turn in the HT motif is stabilized by two H bonds-CO(i-2)-NH(i), with a seven-membered pseudoring (gamma turn) in the backward direction, and NH(i-2)-CO(i), with a 13-membered pseudoring in the forward direction (i being the last residue)--at the C termini. The study was extended to generalize the new three-residue turn (beta-alpha-beta) by using different alpha- and beta-amino acids. Furthermore, the HT motifs were efficiently converted, by an extension with helical oligomers at the C termini, into peptides with novel helix-turn-helix (HTH) tertiary structures. However, this resulted in the destabilization of the beta-alpha-beta turn with the concomitant nucleation of another three-residue turn, alpha-beta-beta, which is stabilized by 11- and 15-membered bifurcated H bonds. Extensive NMR spectroscopic studies were carried out to delineate the secondary and tertiary structures in these peptides, which are further supported by molecular dynamics (MD) investigations.

Design of β-Amino Acid with Backbone–Side Chain Interactions: Stabilization of 14/15-Helix in α/β-Peptides

A new C-linked carbo-β-amino acid, (R)-β-Caa((r)), having a carbohydrate side chain with D-ribo configuration, was prepared from D-glucose by inverting the C-3 stereocenter to introduce constraints/interactions. From the NMR studies it was inferred that the new monomer may participate in additional electrostatic interactions, facilitating and enhancing novel folds in oligomeric peptides derived from it. The α/β-peptides, synthesized from alternating L-Ala and (R)-β-Caa((r)), have shown the presence of 14/15-helix by NMR (in CDCl(3), methanol-d(3) and CD(3)CN), CD and MD calculations. The hybrid peptides showed the presence of electrostatic interactions involving the intraresidue amide proton and the C3-OMe, which helped in the stabilization of the NH(i)···CO(i-4) H-bonds and adoption of 14/15-helix. The importance of such additional interactions has been well defined in recent times to stabilize the folding in a variety of peptidic foldamers. These observations suggest and emphasize that the side chain-backbone interactions are crucial in the stabilization of the desired folding propensity. The designed monomer thus enlarges the opportunities for the synthesis of peptides with novel conformations and expands the repertoire of the foldamers.

Synthesis and Structural Studies of Homooligomers of Geminally Disubstituted β2,2-Amino Acids with Carbohydrate Side Chain

A new class of geminally disubstituted C-linked carbo-β(2,2)-amino acids (β(2,2)-Caa) were prepared from d-glucose. The structures of homooligomeric di-, tetra-, and hexapeptides prepared from (S)-β(2,2)-Caa were studied with NMR (in CDCl(3)), CD, and Molecular Dynamics calculations. These β(2,2)-peptides have shown the presence of stable 6-membered (6-mr) NH(i)···CO(i) intra-residue H-bonded (C(6)) strands. It was found that the strand structures realized in these systems were additionally stabilized by the electrostatic interaction arising due to the proximity of amide proton (NH(i)) to the oxygen of the preceding methoxy group (O(Me)(i-1)) at the C3 carbon of the carbohydrate ring. The new β(2,2)-Caa residues with additional support to H-bonding considerably expand the domain of foldamers.

Synthesis of glycuronamides of amino acids, constituents of microbial polysaccharides and their conversion into neoglycoconjugates of copolymer type

Glycopyranosiduronic acids, amidically linked to amino acids (alanine, serine, threonine, and lysine) were prepared.O-tert-Butyl andNε-tert-butyloxycarbonyl protected amino acidtert-butyl esters were used in ethyl 2-ethoxy-1,2-dihydroquinoline-1-carboxylate promoted condensation with 2-azidoethyl glycosides of glucuronic and galacturonic acid. Reduction of the azido-function followed byN-acryloylation and removal of blocking groups with trifluoroacetic acid gave the target monomers. These were converted into neoglycoconjugates of copolymer type, potentially useful for immunochemical studies.

Self-Assembling Cyclic Tetrapeptide from Alternating C-Linked Carbo-β-amino Acid [(S)-β-Caa] and α-Aminoxy Acid [(R)-Ama]: A Selective Chloride Ion Receptor

A cyclic tetrapeptide is prepared from alternating (S)-beta-Caa (C-linked carbo-beta-amino acid) and (R)-Ama (alpha-aminoxy acid). Extensive NMR (in CDCl(3) solution) and mass spectral (MS) studies show its halide binding capacity, with a special affinity to the chloride ion. At higher concentration it was found to form molecular aggregates as evidenced from transmission electron microscopic and atomic force microscopic analysis, confirming the formation of nanorods.

Helix formation in β/δ‐hybrid peptides: Correspondence between helices of different peptide foldamer classes

An overview on all hydrogen‐bonded helix types, which can be expected in the novel class of β/δ‐hybrid peptides, is provided on the basis of ab initio molecular orbital theory. The results show a considerable potential of different folding patterns, which makes this novel class of peptide foldamers interesting for peptide and protein design. Thus, this study may stimulate the synthesis of such hybrid peptides. The large number of helix types found for β/δ‐hybrid peptides together with the many helices experimentally found and theoretically predicted in the other classes of peptide and hybrid peptide foldamers provide a good basis to establish general correspondence rules for their mutual exchange in peptide sequences. This is done by introduction of the concept of pattern and shape correspondence.