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Design and Partial Synthesis of N, NBis(2-(1H-imidazol-4-yl)ethyl)-3-aminopropanamide for Potential Autism Chelation Therapy

Permanent Link: http://ncf.sobek.ufl.edu/NCFE003740/00001

Material Information

Title: Design and Partial Synthesis of N, NBis(2-(1H-imidazol-4-yl)ethyl)-3-aminopropanamide for Potential Autism Chelation Therapy
Physical Description: Book
Language: English
Creator: Breidbord, Jonathan
Publisher: New College of Florida
Place of Publication: Sarasota, Fla.
Creation Date: 2007
Publication Date: 2007

Subjects

Subjects / Keywords: Autism
Copper
Carnosine
Ligand
Chemistry
Synthesis
Genre: bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, terriorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract: Autism describes a spectrum of neurodevelopmental disorders that have no known etiology, likely reflect defects in early brain development, and are associated with epilepsy in cases of more severe cognitive impairment. Observed in both autism and epilepsy, zinc deficiency leaves copper absorption in the intestines unregulated, thus allowing an individual to become copper-toxic on a normal dietary intake. Accumulation of copper increases excitatory neurosignaling, induces oxidative stress, and contributes to immune-system dysfunction. Chemical correlates of these events have been observed in samples of individuals with a clinical diagnosis of autism. Carnosine is an endogenous dipeptide (Ã�¯ï¿½Ã�� �¢-alanyl-L-histidine) that has produced clinical gains when orally administered as a supplement to children with autism or epilepsy. Since therapeutic effects may be limited by its suboptimal formation of copper(II) complexes, a carnosine analogue was proposed for optimal binding to copper. Towards retention of its satisfactory clinical features such as water solubility and suitability as a supplement, minimal modifications were made to the parent structure. The resulting ligand, N,N-bis(2-(1H-imidazol-4-yl)ethyl)-3-aminopropanamide, retains carnosineÃ�¢ï¿� �½Ã¯Â¿Â½s Ã�¯ï¿½Ã�¢-alanyl residue and 4-ethylimidazole moiety and contains an additional 4-ethylimidazole moiety to enhance the formation of stable copper(II) complexes with distorted square pyramidal geometry as predicted by molecular models. The proposed synthetic scheme involves diazotization of histamine, chlorination of the resulting alcohol, subsequent alkylation of histamine by the chloride, coupling of this product with Boc-protected Ã�¯ï� �¿Â½Ã�¢-alanine, and a final deprotection reaction to yield the novel tripodal ligand. As part of this thesis, published methods for the multistep synthesis of 4-chloroethylimidazole were compared and an alkylation procedure was developed for the novel synthesis of a mixture containing the desired bis(4-imidazolylethyl)amine product and excess histamine nucleophile as major products. Although efforts to purify this mixture were unsuccessful, results of this alkylation reaction improve upon those from published methods to date.
Statement of Responsibility: by Jonathan Breidbord
Thesis: Thesis (B.A.) -- New College of Florida, 2007
Electronic Access: RESTRICTED TO NCF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE
Bibliography: Includes bibliographical references.
Source of Description: This bibliographic record is available under the Creative Commons CC0 public domain dedication. The New College of Florida, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Local: Faculty Sponsor: Sherman, Suzanne

Record Information

Source Institution: New College of Florida
Holding Location: New College of Florida
Rights Management: Applicable rights reserved.
Classification: local - S.T. 2007 B83
System ID: NCFE003740:00001

Permanent Link: http://ncf.sobek.ufl.edu/NCFE003740/00001

Material Information

Title: Design and Partial Synthesis of N, NBis(2-(1H-imidazol-4-yl)ethyl)-3-aminopropanamide for Potential Autism Chelation Therapy
Physical Description: Book
Language: English
Creator: Breidbord, Jonathan
Publisher: New College of Florida
Place of Publication: Sarasota, Fla.
Creation Date: 2007
Publication Date: 2007

Subjects

Subjects / Keywords: Autism
Copper
Carnosine
Ligand
Chemistry
Synthesis
Genre: bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, terriorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract: Autism describes a spectrum of neurodevelopmental disorders that have no known etiology, likely reflect defects in early brain development, and are associated with epilepsy in cases of more severe cognitive impairment. Observed in both autism and epilepsy, zinc deficiency leaves copper absorption in the intestines unregulated, thus allowing an individual to become copper-toxic on a normal dietary intake. Accumulation of copper increases excitatory neurosignaling, induces oxidative stress, and contributes to immune-system dysfunction. Chemical correlates of these events have been observed in samples of individuals with a clinical diagnosis of autism. Carnosine is an endogenous dipeptide (Ã�¯ï¿½Ã�� �¢-alanyl-L-histidine) that has produced clinical gains when orally administered as a supplement to children with autism or epilepsy. Since therapeutic effects may be limited by its suboptimal formation of copper(II) complexes, a carnosine analogue was proposed for optimal binding to copper. Towards retention of its satisfactory clinical features such as water solubility and suitability as a supplement, minimal modifications were made to the parent structure. The resulting ligand, N,N-bis(2-(1H-imidazol-4-yl)ethyl)-3-aminopropanamide, retains carnosineÃ�¢ï¿� �½Ã¯Â¿Â½s Ã�¯ï¿½Ã�¢-alanyl residue and 4-ethylimidazole moiety and contains an additional 4-ethylimidazole moiety to enhance the formation of stable copper(II) complexes with distorted square pyramidal geometry as predicted by molecular models. The proposed synthetic scheme involves diazotization of histamine, chlorination of the resulting alcohol, subsequent alkylation of histamine by the chloride, coupling of this product with Boc-protected Ã�¯ï� �¿Â½Ã�¢-alanine, and a final deprotection reaction to yield the novel tripodal ligand. As part of this thesis, published methods for the multistep synthesis of 4-chloroethylimidazole were compared and an alkylation procedure was developed for the novel synthesis of a mixture containing the desired bis(4-imidazolylethyl)amine product and excess histamine nucleophile as major products. Although efforts to purify this mixture were unsuccessful, results of this alkylation reaction improve upon those from published methods to date.
Statement of Responsibility: by Jonathan Breidbord
Thesis: Thesis (B.A.) -- New College of Florida, 2007
Electronic Access: RESTRICTED TO NCF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE
Bibliography: Includes bibliographical references.
Source of Description: This bibliographic record is available under the Creative Commons CC0 public domain dedication. The New College of Florida, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Local: Faculty Sponsor: Sherman, Suzanne

Record Information

Source Institution: New College of Florida
Holding Location: New College of Florida
Rights Management: Applicable rights reserved.
Classification: local - S.T. 2007 B83
System ID: NCFE003740:00001

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