Kallaganti V. S. Ramakrishna

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.

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.

A diastereoselective synthesis of tetrahydro- and dihydro-pyrido[2,3-c]coumarin derivatives via a one-pot three-component Povarov reaction catalyzed by bismuth(III) chloride

A diastereoselective synthesis of tetrahydro- and dihydro-pyrido[2,3-c]coumarin derivatives has been achieved via a one-pot three-component aza-Diels-Alder reaction of aromatic aldehydes, 3-aminocoumarin and dienophiles catalyzed by BiCl3. NOE studies proved that exo-isomers were obtained in all cases with high selectivity. The reaction proceeded at room temperature providing good yields of products as well as applicability on a wide range of substrates. Among all the synthesized derivatives, compounds 4i and 4k showed promising DPPH radical scavenging activity as compared to other tested derivatives.

A Double Activation Method for the Conversion of Vinyl Epoxides into vic-Amino Alcohols and Chiral Benzoxazine/Quinoxaline Derivatives

A new method for the synthesis of 1,2-syn-vic amino alcohols (with double inversion of configuration) from vinyl epoxides, by the amination of a π-allyl palladium-borate complex generated by using Pd(0) and phenyl-o-phenylene borate (a double activation technique), is reported. Further, this new method with broad functional group compatibility was extended to a one-pot/two-step synthesis of chiral benzoxazine and quinoxaline derivatives.

Synthesis of (−) cephalosporolide E and (+) cephalosporolide F utilizing the vinylogous Mukaiyama type reaction with an α-chloro sulfide

The synthesis of cephalosporolide E and F is described utilizing diastereoselective reduction of a propargylic ketone using a Noyori catalyst to create the C6 carbinol stereogenic center. A vinylogous silylketene acetal addition to an α-chloro sulfide is exploited for stereoselective carbon–carbon bond formation and introduction of the butenolide moiety. Oxidative radical cyclization is utilized for the creation of the [5,5]-spiroketal moiety.

Asymmetric Total Syntheses of Two Possible Diastereomers of Gliomasolide E and Its Structural Elucidation

The first total syntheses of two possible diastereomers of gliomasolide E, a 14-membered macrolides isolated from the marine sponge Phakellia fusca Thiele, which was collected from the South China Sea, is reported. Highlights of the synthesis include macrolactonization through intramolecular Horner-Wadsworth-Emmons olefination, Yamaguchi-Hirao alkynylation, and base-induced elimination reactions for propargyl alcohol synthesis as the key reactions. Detailed comparison of their 1H and 13C NMR (1D and 2D NMR data) and specific rotation with those of the natural product revealed that the absolute stereochemistry of gliomasolide E should be (2E,5R,7R,9R,13R).

Biological evaluation of 3-hydroxybenzyl alcohol, an extrolite produced by Aspergillus nidulans strain KZR-132

The aim of the study was to purify and characterize a bioactive compound from Aspergillus nidulans strain KZR‐132 and its biological evaluation.

The exploration of Kemp's triacid (KTA) as the core for the synthesis of 3-fold symmetric 23-cyclophane, 22-cyclophane and novel linker directed designs

For the first time, two units of KTA have been linked to three units of cyst-di-OMe. The reaction is noteworthy since it involves the formation of six amide bonds leading to a three-fold symmetric 23-cyclophane (3) harboring a cluster of three S–S bridges. The major product is a di-imide (4), arising from the interaction of a cystine NH with a neighbouring activated ester. A third reaction of tethering KTA with a single cyst-di-OMe unit afforded the flexible compound 6 and, with benzidine, the novel linker directed 7 with orthogonally disposed anchor modules.