Abstract
Routes to novel phosphine-peptide hybrid scaffolds for enantioselective catalysis through phosphinecontaining
amino acid analogues were investigated. P,P-dichlorophenylphosphine was used as a
precursor in the exploration of constructing phosphine-containing building blocks for combination with
solid-phase peptide synthesis. Nucleophilic substitution on P,P-dichlorophenylphosphine with
ethynylmagnesiumbromide or TIPS/TMS-acetylides did not yield the desired dialkynated phosphine. A
novel triphenyl phosphine sulfide amino acid analogue was observed. Two triphenylphosphine-based
amino acid analogues were obtained on solid support and one of them was utilized as an anchor for
elongation of peptides showing compatibility with solid-phase peptide synthesis. An unexpected route
to heterobifunctional organophosphorus scaffolds containing an ethylene glycol moiety and a
carboxylic acid function was discovered and the compounds were structurally elucidated via NMR and
mass spectroscopy. Two of these compounds were incorporated into peptides. An existing method of
obtaining peptides containing secondary amines in the peptide backbone have been expanded for
incorporation of functional amino acids as well (His(Trt), Gln, Gln(Trt), Cys(tBu), Thr(OtBu), azido-
Dab, Asp(OtBu), Arg(Pmc))) yielding a range of novel modified peptides. Peptides containing one
secondary amine were phosphinylated and captured as either phosphine-boranes or oxides. Both borane
and oxide protection of phosphine-peptide hybrids allowed deprotection of the peptide side-chain
protecting groups while leaving the phosphine group untouched. Treating this class of borane-protected
phosphine-peptide hybrids with DABCO in toluene liberated the phosphine-borane group from the
peptide. Treating mono-phosphinylated peptides with allyl palladium chloride dimer did not yield an
observable phosphine-palladium complex. A peptide containing two secondary amine sites was
synthesized, phosphinylated and complexed to respectively palladium and copper. The palladium
complex was utilized successfully as a palladium catalyst in a model Sonogashira reaction and the
copper complex was utilized successfully in a copper(I)-catalyzed alkyne-azide cycloaddition.
amino acid analogues were investigated. P,P-dichlorophenylphosphine was used as a
precursor in the exploration of constructing phosphine-containing building blocks for combination with
solid-phase peptide synthesis. Nucleophilic substitution on P,P-dichlorophenylphosphine with
ethynylmagnesiumbromide or TIPS/TMS-acetylides did not yield the desired dialkynated phosphine. A
novel triphenyl phosphine sulfide amino acid analogue was observed. Two triphenylphosphine-based
amino acid analogues were obtained on solid support and one of them was utilized as an anchor for
elongation of peptides showing compatibility with solid-phase peptide synthesis. An unexpected route
to heterobifunctional organophosphorus scaffolds containing an ethylene glycol moiety and a
carboxylic acid function was discovered and the compounds were structurally elucidated via NMR and
mass spectroscopy. Two of these compounds were incorporated into peptides. An existing method of
obtaining peptides containing secondary amines in the peptide backbone have been expanded for
incorporation of functional amino acids as well (His(Trt), Gln, Gln(Trt), Cys(tBu), Thr(OtBu), azido-
Dab, Asp(OtBu), Arg(Pmc))) yielding a range of novel modified peptides. Peptides containing one
secondary amine were phosphinylated and captured as either phosphine-boranes or oxides. Both borane
and oxide protection of phosphine-peptide hybrids allowed deprotection of the peptide side-chain
protecting groups while leaving the phosphine group untouched. Treating this class of borane-protected
phosphine-peptide hybrids with DABCO in toluene liberated the phosphine-borane group from the
peptide. Treating mono-phosphinylated peptides with allyl palladium chloride dimer did not yield an
observable phosphine-palladium complex. A peptide containing two secondary amine sites was
synthesized, phosphinylated and complexed to respectively palladium and copper. The palladium
complex was utilized successfully as a palladium catalyst in a model Sonogashira reaction and the
copper complex was utilized successfully in a copper(I)-catalyzed alkyne-azide cycloaddition.
| Originalsprog | Engelsk |
|---|
| Forlag | Department of Chemistry, Faculty of Science, University of Copenhagen |
|---|---|
| Antal sider | 175 |
| Status | Udgivet - 2017 |