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4-(3-Hydroxy-4-methylpentyl)phenylacetic acid as a new linker for the solid phase synthesis of peptides with Boc chemistry
Stockholm University, Faculty of Science, Department of Neurochemistry and Neurotoxicology.
Stockholm University, Faculty of Science, Department of Neurochemistry and Neurotoxicology.
Stockholm University, Faculty of Science, Department of Neurochemistry and Neurotoxicology.ORCID iD: 0000-0003-1003-6472
1999 (English)In: Tetrahedron Letters, ISSN 0040-4039, E-ISSN 1359-8562, Vol. 40, no 2, 377-380 p.Article in journal (Refereed) Published
Abstract [en]

The anchoring the first amino acid in Boc chemistry to a 4-(3-hydroxy-4-methylpentyl)phenylacetic acid linker is described and compared to the conventional Pam resin. The peptidyl-4-(4-methyl-3-pentoxy)phenylacetamide linkage is slightly more stable to TFA than the Pam linker but in contrast to the Pam linker stable to cleavage of benzylic protective groups with TFMSA/DMS/TFA mixtures. This allows a mild and convenient two step deprotection procedure using the “low TFMSA-high HF”. In HF this new linker reacts preferentially in an intramolecular reaction forming a tetrahydronaphthalene derivative.

Place, publisher, year, edition, pages
1999. Vol. 40, no 2, 377-380 p.
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:su:diva-25837DOI: 10.1016/S0040-4039(98)02316-8OAI: oai:DiVA.org:su-25837DiVA: diva2:200647
Available from: 2006-04-07 Created: 2006-04-07 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Methodological studies in solid phase synthesis: Linkers and applications of multi-component condensations
Open this publication in new window or tab >>Methodological studies in solid phase synthesis: Linkers and applications of multi-component condensations
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Solid phase synthesis has become an increasingly important tool in the synthesis of oligopolymers and small organic molecules. This thesis covers three important areas in the solid phase synthesis technique: linker strategies, reduction methods and novel routes to complex heterocycles.

The synthesis of the OMPPA [4-(3-hydroxy-4-metylpentyl)phenyl acetic acid] linker is described. This linker is compatible with the Boc/Bzl protective group strategy, and yields peptide acids upon cleavage from solid support. The OMPPA linker is stable towards “low-acid” treatment and is self-scavenging during final cleavage of the peptide product from solid support. These properties are beneficial for peptide purity and yields.

The synthesis of the HMPPA [3-(4-hydroxymethylphenylsulfanyl)propanoic acid] linker is described. This safety catch linker is compatible with both Fmoc/tBu- and Boc/Bzl protective group strategies in solid phase peptide synthesis. The HMPPA linker is stable towards super acids yet final cleavage from solid support is performed by a relatively mild reductive acidolysis method, yielding peptide acids. It is suggested that this linker may be useful when synthesizing cyclic peptides on solid support. A new facile method for reducing cystine moieties is described. Adding metallic zinc to cystine containing peptides and proteins dissolved in slightly acidic aqueous and/or non-aqueous solutions, results in rapid disulfide reduction. This method is compatible with functional groups commonly present in peptides and proteins. The solid phase synthesis of oxygen-bridged tetrahydropyridones via a multi-component condensation reaction is described. Expected products were obtained in reasonable yields using both aromatic- and aliphatic ketones. This class of compounds has the general physico-chemical properties that are typical for drugs with high pharmacological activity.

Place, publisher, year, edition, pages
Stockholm: Institutionen för neurokemi, 2006. 87 p.
Keyword
Solid phase peptide synthesis, solid phase organic chemistry, linkers, self-scavenging, safety catch linker, cyclic peptides, reductive acidolysis, disulfides, reduction, metallic zinc, multi-component condensations, combinatorial chemistry
National Category
Neurosciences
Identifiers
urn:nbn:se:su:diva-922 (URN)978-91-7155-2 (ISBN)
Public defence
2006-04-27, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 12 A, Stockholm, 13:00
Opponent
Supervisors
Available from: 2006-04-07 Created: 2006-04-07Bibliographically approved

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