SCHIFF BASE SYNTHONS IN AMINO ACID CHEMISTRY

Summary

Principal Investigator: MARTIN J O'DONNELL
Abstract: The utilization of both natural and unnatural alpha-amino acids in practically all areas of the physical and life sciences continues to grow at an impressive rate. In addition to their key biological role as the "building blocks" of peptides, proteins and other natural products, the alpha-amino acids as well as peptidomimetics are used extensively in the pharmaceutical, agrochemical and food industries. Amino acids have also been used in total synthesis and other synthetic studies, both as sources of chirality in final products and as chiral auxiliaries, reagents and catalysts for asymmetric synthesis. Methods for the asymmetric synthesis of alpha-amino acids, especially those that involve stereocontrol, are of special interest. Because of this widespread use, new and versatile methods for both the small and large-scale preparation of natural and structurally diversified alpha-amino acid derivatives as well as peptidomimetics are important. The long-term objective of this research is the development and application of synthetic methods for the preparation of structurally diversified amino acids, peptides, and peptidomimetics. Synthetic studies will be pursued using two complementary systems: anionic and cationic amino acid equivalents. Using enantiocontrol elements that are derived from natural products or are commercially available it is possible to prepare amino acids of high optical purity. Solid-phase methodologies will be used for the development of chemistry to make demonstration libraries of compounds in a combinatorial fashion. Areas of particular interest include the synthesis of fluorine-containing amino acid derivatives as well as conformationally restricted amino acids and peptidomimetics. The chemistry that has been developed concerning the use of Schiff base synthons for the synthesis of amino acids is being utilized by the scientific community as evidenced by publications and patents by others. A key point of focus in this research will be to continue to develop practical and easy-to-use methods that can lead to potential drugs.
Funding Period: 1980-08-01 - 2009-01-31
more information: NIH RePORT

Top Publications

  1. pmc Unexpected hydrolytic instability of N-acylated amino acid amides and peptides
    J Geno Samaritoni
    Department of Chemistry and Chemical Biology, Indiana University Purdue University Indianapolis, Indianapolis, Indiana 46202, United States
    J Org Chem 79:3140-51. 2014
  2. ncbi Solid-phase synthesis of amino- and carboxyl-functionalized unnatural alpha-amino acid amides
    William L Scott
    Department of Chemistry and Chemical Biology, Indiana University Purdue University Indianapolis, Indianapolis, Indiana 46202 3274, USA
    Org Lett 11:3558-61. 2009
  3. ncbi Solid-phase synthetic route to multiple derivatives of a fundamental peptide unit
    William L Scott
    Department of Chemistry and Chemical Biology, Indiana University Purdue University, Indianapolis, 402 N Blackford Street, Indianapolis, IN 46202, USA
    Molecules 15:4961-83. 2010
  4. ncbi Catalytic enantioselective synthesis of glutamic acid derivatives via tandem conjugate addition-elimination of activated allylic acetates under chiral PTC conditions
    P Veeraraghavan Ramachandran
    Department of Chemistry, Purdue University, West Lafayette, Indiana 47907 2084, USA
    J Am Chem Soc 127:13450-1. 2005
  5. ncbi Solid-phase synthesis of multiple classes of peptidomimetics from versatile resin-bound aldehyde intermediates
    William L Scott
    Department of Chemistry and Chemical Biology, Indiana University Purdue University Indianapolis, Indianapolis, Indiana 46202 3274, USA
    J Am Chem Soc 129:7077-88. 2007
  6. pmc Distributed Drug Discovery, Part 3: using D(3) methodology to synthesize analogs of an anti-melanoma compound
    William L Scott
    Department of Chemistry and Chemical Biology, Indiana University Purdue University Indianapolis, Indianapolis, Indiana 46202 3274, USA
    J Comb Chem 11:34-43. 2009
  7. pmc Distributed Drug Discovery, Part 2: global rehearsal of alkylating agents for the synthesis of resin-bound unnatural amino acids and virtual D(3) catalog construction
    William L Scott
    Department of Chemistry and Chemical Biology, Indiana University Purdue University, Indianapolis, Indiana 46202 3274, USA
    J Comb Chem 11:14-33. 2009

Scientific Experts

  • William L Scott
  • J Subash Chandra
  • J Geno Samaritoni
  • MARTIN J O'DONNELL
  • P Veeraraghavan Ramachandran
  • Alexus T Copes
  • Demarcus K Crews
  • Corydon Wilson
  • Courtney Glos
  • Andre L Thompson
  • M Venkat Ram Reddy
  • Sateesh Madhi
  • Layla Bland-Berry

Detail Information

Publications8

  1. pmc Unexpected hydrolytic instability of N-acylated amino acid amides and peptides
    J Geno Samaritoni
    Department of Chemistry and Chemical Biology, Indiana University Purdue University Indianapolis, Indianapolis, Indiana 46202, United States
    J Org Chem 79:3140-51. 2014
    ....
  2. ncbi Solid-phase synthesis of amino- and carboxyl-functionalized unnatural alpha-amino acid amides
    William L Scott
    Department of Chemistry and Chemical Biology, Indiana University Purdue University Indianapolis, Indianapolis, Indiana 46202 3274, USA
    Org Lett 11:3558-61. 2009
    ..Alkylating agents with a range of reactivities and normal and branched primary amines give good results. Utility was demonstrated by the synthesis of a series of protected phosphotyrosine mimetics...
  3. ncbi Solid-phase synthetic route to multiple derivatives of a fundamental peptide unit
    William L Scott
    Department of Chemistry and Chemical Biology, Indiana University Purdue University, Indianapolis, 402 N Blackford Street, Indianapolis, IN 46202, USA
    Molecules 15:4961-83. 2010
    ..In a single solid-phase sequence, compatible with basic amine substituents, three-point variation is performed at the amino acid a-carbon and the amino and carboxyl functionalities...
  4. ncbi Catalytic enantioselective synthesis of glutamic acid derivatives via tandem conjugate addition-elimination of activated allylic acetates under chiral PTC conditions
    P Veeraraghavan Ramachandran
    Department of Chemistry, Purdue University, West Lafayette, Indiana 47907 2084, USA
    J Am Chem Soc 127:13450-1. 2005
    ..A variety of structural types of allylic acetates have been reacted with the benzophenone imine of glycine tert-butyl ester to give the products in good to excellent yields and enantioselectivities (63-92% yield, 80-97% ee, 8 cases)...
  5. ncbi Solid-phase synthesis of multiple classes of peptidomimetics from versatile resin-bound aldehyde intermediates
    William L Scott
    Department of Chemistry and Chemical Biology, Indiana University Purdue University Indianapolis, Indianapolis, Indiana 46202 3274, USA
    J Am Chem Soc 129:7077-88. 2007
    ....
  6. pmc Distributed Drug Discovery, Part 3: using D(3) methodology to synthesize analogs of an anti-melanoma compound
    William L Scott
    Department of Chemistry and Chemical Biology, Indiana University Purdue University Indianapolis, Indianapolis, Indiana 46202 3274, USA
    J Comb Chem 11:34-43. 2009
    ..As a continuing part of the Distributed Drug Discovery program, a virtual D(3) catalog based on this work was then enumerated and is made freely available to the global scientific community...
  7. pmc Distributed Drug Discovery, Part 2: global rehearsal of alkylating agents for the synthesis of resin-bound unnatural amino acids and virtual D(3) catalog construction
    William L Scott
    Department of Chemistry and Chemical Biology, Indiana University Purdue University, Indianapolis, Indiana 46202 3274, USA
    J Comb Chem 11:14-33. 2009
    ....