N. Narendra

Chiral N-Fmoc-β-Amino Alkyl Isonitriles Derived from Amino Acids: First Synthesis and Application in 1-Substituted Tetrazole Synthesis

A novel class of optically active N-Fmoc-protected amino isonitriles has been described for the first time. Conversion of the carboxyl group of Fmoc-beta-amino acids into an isocyano group has resulted in a new class of N-urethane-protected amino isonitriles. All the isonitriles have been isolated as stable solids, purified, and completely characterized. A synthetic application of the obtained isonitriles has also been demonstrated through the synthesis of 1-substituted tetrazole analogues of amino acids via a 2 + 3 cycloaddition with trimethylsilyl azide.

Synthesis of Selenoxo Peptides and Oligoselenoxo Peptides Employing LiAlHSeH

Synthesis of selenoxo peptides by the treatment of N(α)-protected peptide esters with a combination of PCl(5) and LiAlHSeH is delineated. The method is simple, high-yielding, and free from racemization. Thus obtained selenoxo peptides are used as units for N-terminal chain extension through N(α)-deprotection/coupling to yield peptide-selenoxo peptide hybrids. Multiple selenation is demonstrated by conversion of two peptide bonds of tripeptides into selenoxo peptide bonds. Amino acid derived arylamides are also converted into aryl selenoamides. C(6)H(5)-CSeNH-Val-OMe 8f is obtained as single crystal, and its structure was determined through X-ray diffraction study.

Click Chemistry Aided Synthesis of 1,4-Substituted 1,2,3-Triazole Based N-Fmoc Protected -Amino Acids: Isolation, Characterization and Synthesis of Novel Triazole Based Unnatural Amino Acids

A new class of 1,4-substituted 1,2,3-triazole-based unnatural amino acids is demonstrated by employing click reaction between N-Fmoc amino alkyl azides and propiolic acid. The resulting unnatural amino acids were isolated and then subjected to Fmoc deprotection to isolate 1,2,3-triazole based amino acids as stable solids. These new class of molecules were also used for chain extension from both N- and C-terminals to synthesize dipeptidomimetics bearing 1,2,3-triazole moiety in the backbone.

Synthesis of 4-Amino-Thiazole Analogs of Fmoc-Amino Acids and Thiazole Linked N-Orthogonally Protected Dipeptidomimetics

We report a one pot synthesis of Fmoc amino acid derived 4-amino-thiazole derivatives and thiazole linked N-orthogonally protected dipeptidomimetics by the condensation of N(alpha)-Fmoc alpha-halomethylketones with thiourea and Boc/Z-alpha-amino acid thioamides via modified Hantzch protocol. Side chain modified Fmoc amino acids containing 4-amino thiazole moiety have also been synthesized following the similar protocol.

A Facile One-pot Synthesis of Nα-Urethane Protected 3-Amino Alkyl Isoxazole-5-Carboxylic Acids and their Utility for the Preparation of Isoxazole-Linked Peptidomimetics

Cu(I) catalyzed [3+2] cycloaddition of in situ generated Nα-Fmoc/Boc/Z-protected amino alkyl nitrile oxide with propiolic acid has led to a new class of 3,5-disubstituted isoxazole-bearing amino acid derivatives. The click chemistry protocol described herein is efficient in furnishing the isoxazole embedded amino acids. These unnatural synthons were subjected to chain extension on N- as well as C-termini to obtain 3,5-disubstituted isoxazole bearing di and tripeptidomimetics.

Peptidomimetics Through Click Chemistry: Synthesis of Novel β-Keto Triazole Acids from N-Protected Amino Acids

An efficient procedure for the preparation of azidomethylketones from N-urethane protected amino acids and their application in Cu(I) catalyzed azide-alkyne cycloaddition reaction are described. The synthesis has been carried out under mild conditions with all the commonly used urethane protected (Fmoc, Boc and Z) amino acids and the desired azides/triazoles were obtained in good yields. Incorporation of these triazole amino acids into small peptides generating dipeptidomimetics containing β-keto triazole units has also been demonstrated.

Synthesis of Ureido-Linked Glycosylated Amino Acids from N α-Fmoc-Asp/Glu-5-oxazolidinones and Their Application to Neoglycopeptide Synthesis

Abstract A simple route for the synthesis of ureido-linked glycosylated amino acids has been described. The key step involves the reaction of isocyanates derived from N α-Fmoc-Asp/Glu-5-oxazolidinones 1 with glycosyl amines followed by hydrolysis. The resulting ureido-linked glycosylated amino acids have been incorporated into peptides. The overall procedure is simple, high-yielding, and involves fewer steps.

Synthesis of N-urethane protected β-amino alcohols employing N-(protected-α-aminoacyl)benzotriazoles

A simple and racemisation-free synthesis of N-urethane protected α-amino/peptidyl alcohols by the reduction of the corresponding easily accessible N-acylbenzotriazoles is described. The method is practical, straightforward, fast and efficient for the synthesis of amino/peptidyl alcohols. All the alcohols made were isolated in high yields and purity.

CuI-Promoted One-Pot Synthesis of N-Boc Protected β-Ketotriazole Amino Acids: Application in the Synthesis of New Class of Dipeptidomimetics

One-pot click chemistry of N(α)-Boc-bromomethylketones, NaN3 and propiolic acid affords N-Boc protected 1,4-disubstituted 1,2,3-β-ketotriazole acids in good to excellent yield. The use of CuI as catalyst and DMSO as solvent leads the click reaction to efficient, practical and column-free preparation of the title compounds. The utility of the resulting unnatural amino acids as building blocks to prepare triazole possessing peptidomimetics is also delineated.

An Efficient and Epimerization Free Synthesis of C-Terminal Arylamides Derived from α-Amino Acids and Peptide Acids via T3P Activation

A high yield and rapid synthesis of enantiomerically pure Nα-protected amino/peptide acid arylamides using n-propylphosphonic anhydride (T3P) in presence of N-methylmorpholine is described. The generality of the reaction has been studied for various Nα-protected amino acids with diverse range of aromatic amines and coumarin derivatives.