Tushar Kanti Chakraborty

α-phenylglycinol as chiral auxiliary in diastereoselective strecker synthesis of α-amino acids

The high diastereoselectivity achieved in Strecker synthesis using inexpensive α-phenylglycinol as chiral auxiliary and its facile removal by oxidative cleavage make it an ideal choice for the large scale preparations of optically active α-amino acids specially α-arylglycines present abundantly in glycopeptide antibiotics. A number of chiral amino acids are synthesized following this method. Also molecular mechanics calculations are carried out to explain the observed diastereoselection.

Sugar amino acids and related molecules: some recent developments

To meet the growing demands for the development of new molecular entities for discovering new drugs and materials, organic chemists have started working on many new concepts that can help to assimilate knowledge-based structural diversities more efficiently than ever before. Emulating the basic principles followed by Nature to build its vast repertoire of biomolecules, organic chemists are developing many novel multifunctional building blocks and using them to create ‘nature-like’ and yet unnatural organic molecules. Sugar amino acids constitute an important class of such polyfunctional scaffolds where the carboxyl, amino and hydroxyl termini provide an excellent opportunity to organic chemists to create structural diversities akin to Nature’s molecular arsenal. In recent years, sugar amino acids have been used extensively in the area of peptidomimetic studies. Advances made in the area of combinatorial chemistry can provide the necessary technological support for rapid compilations of sugar amino acidbased libraries exploiting the diversities of their carbohydrate frameworks and well-developed solid-phase peptide synthesis methods. This perspective article chronicles some of the recent applications of various sugar amino acids, furan amino acids, pyrrole amino acids etc. and many other related building blocks in wide-ranging peptidomimetic studies

Diastereoselective Strecker synthesis using α-phenylglycinol as chiral auxiliary

Use of α-phenylglycinol as chiral auxiliary in Strecker synthesis ensures high diastereoselectivity and its easy removal by oxidative cleavage allows large scale preparation of optically active α-amino acids.

Studies directed towards the synthesis of immunosuppressive agent FK-506 : synthesis of the entire bottom-half

An efficient approach has been developed to construct the entire TOP-HALF of FK-506 involving Grignard reaction of a C-29 bromide with a C-27 methylketo fragment.

Synthetic studies toward potent cytotoxic agents amphidinolides G and H: Synthesis of the entire C15C26 moiety of the top half

Stereoselective synthesis of the entire (16S, 18S, 21R, 22S, 23R, 25R)-C15C26 segment 1 of amphidinolides G and H has been achieved for the first time following a highly efficient convergent strategy.

Sugar amino acids in designing new molecules

Emulating the basic principles followed by Nature to build its vast repertoire of biomolecules, organic chemists are developing many novel multifunctional building blocks and using them to create ‘nature-like’ and yet unnatural organic molecules. Sugar amino acids constitute an important class of such polyfunctional scaffolds where the carboxyl, amino and hydroxyl termini provide an excellent opportunity to organic chemists to create structural diversities akin to Nature’s molecular arsenal. This article describes some of our works on various sugar amino acids and many other related building blocks, like furan amino acids, pyrrole amino acids etc. used in wide-ranging peptidomimetic studies. Published in 2005.

Chemistry of potent anti-cancer compounds, amphidinolides.

Amphidinolides A-V represent a family of cytotoxic marine natural products with diverse structural features and pronounced biological activities. Kobayashi and his research group have been reporting over the years the discoveries of these remarkable molecules, one after another, since 1986 when the first report of the series appeared. Thanks to their perseverance and painstaking research, the family is still expanding. The unique structural features and biological activity profiles of these macrolides have obviously attracted the attention of organic chemists worldwide. The total syntheses of three members of the family, amphidinolides J, K and P, have already been achieved. This review tries to chronicle the fascinating chemistries of amphidinolides, studies on the syntheses of some of these molecules and their biological activity profiles.

The first synthesis of C-terminal biphenyl moiety of vancomycin

Abstract A successful Palladium catalysed intramolecular coupling of phenyl rings corresponding to amino acids (R)-4-hydroxyphenylglycine ( 5 ) and (S)-3,5-dihydroxyphenylglycine ( 7 ) of vancomycin is achieved.

Synthesis of chiral 1,3-diols by radical-mediated regioselective opening of 2,3-epoxy alcohols using cp2TiCl

Radical-mediated opening of chiral 2,3-epoxy alcohols 1a–e, regioselectively at the 2-position, using cp2TiCl in the absence of a hydrogen source leads to the formation of the 1,3-diols 2a–e.

Selective Targeting of G-Quadruplex Using Furan-Based Cyclic Homooligopeptides: Effect on c-MYC Expression

Quadruplex-specific molecules can serve as suitable drugs in cancer therapy. We have synthesized a pair of furan-based cyclic homooligopeptides, ligand 1 and ligand 2, to specifically target G-quadruplexes. We have shown by CD spectroscopy and UV melting that these ligands can effectively induce G-quadruplex structures in the G-rich 22-mer c-MYC DNA sequence and further stabilize the structure. Equilibrium binding constants measured by isothermal titration calorimeter methods indicate a high affinity of the ligands for the quadruplex structures (K ∼ 10(7) M(-1)) and no affinity for the duplex DNA, demonstrating that these ligands are selective for G-quadruplex structures. Surface plasmon resonance was also used to compute the binding while fluorescence resonance energy transfer-based assay was additionally used to confirm the selectivity. Moreover, using real time PCR we observed up to 90% downregulation of c-MYC transcripts after 24 h of ligand treatment in HeLa cells. Using a luciferase assay we show the downregulation of the protein levels. Fluorescent-assisted cell sorter-based cell cycle analysis showed a prominent arrest of cells in the sub-G1 stage upon treatment of ligands that leads toward apoptosis. Altogether, these experiments support the hypothesis that the present molecules are effective in specifically binding and stabilizing quadruplexes and provide a suitable scaffold to develop into a quadruplex-targeting therapeutic agent.