Synthesis of a New Turn Mimic Bearing a β-Lactam Moiety

Abstract

A new turn mimic derived from PLG (prolyl-leucyl-glycine amide) containing a β-lactam in the turn area has been prepared. The β-lactam moiety was furnished by treating an Fmoc-protected leucine-derived diazo ketone 2 with a benzylidene-protected glycine ester in a photochemically induced Staudinger-type reaction. The trans-substituted β-lactams 3a/b are formed in 70% yield (dr 70:30). Separation of the isomers, deprotection and attachment of Fmoc-proline using the pentafluorphenyl ester activation protocol yielded the protected peptidomimetic 4 in 93% yield. Deprotection

Synthesis of tetracyclic dibenzo[ b , f ][1,4]oxazepine-fused β-lactams via visible-light-induced Staudinger annulation

“…According to previous studies, 8,9,11 a plausible reaction mechanism for this transformation is illustrated in Scheme 5. Firstly, visible light promoted Wolff rearrangement of α-diazo ketone 2a gives the ketene intermediate 2a′ in situ .…”

Synthesis of tetracyclic dibenzo[ b , f ][1,4]oxazepine-fused β-lactams via visible-light-induced Staudinger annulation

“…According to previous studies, 8,9,11 a plausible reaction mechanism for this transformation is illustrated in Scheme 5. Firstly, visible light promoted Wolff rearrangement of α-diazo ketone 2a gives the ketene intermediate 2a′ in situ .…”

Quaternary α,α-2-Oxoazepane α-Amino Acids: Synthesis from Ornithine-Derived β-Lactams and Incorporation into Model Dipeptides

“…Oxidation of the 2-azetidinones 12 – 15 with K 2 S 2 O 8 /K 2 HPO 4 in CH 3 CN/H 2 O at 75 °C under bubbled Ar yielded the expected 1-unsubstituted analogues 16 – 19 in moderate yield (30–60%). No big differences were found in the oxidation of the 1-Pmb Orn derivative 12 and its Dmb analogue 13 ; therefore the Pmb group was selected, due to better yields in the cyclization to the β-lactam derivatives.…”

Synthetic turn mimetics and hairpin nucleators: Quo Vadimus?

“…57 It has been successful to a larger extent in imitating the topology of natural peptide components with improved binding and selectivity. Integrating constrained moieties witnessed the use of proline derivatives, 58 a-aminoxy acids, 59 g-turn inducing 2-alkyl-2carboxyazetidines, 60 b-lactam-derived amino acid, 61 and so on. To restrict the reverse turn architecture, one of the easiest ways is to integrate torsionally constrained amino acids into the peptide backbone.…”

Synthesis of tetracyclic dibenzo[ b , f ][1,4]oxazepine-fused β-lactams via visible-light-induced Staudinger annulation

“…According to previous studies, 8,9,11 a plausible reaction mechanism for this transformation is illustrated in Scheme 5. Firstly, visible light promoted Wolff rearrangement of α-diazo ketone 2a gives the ketene intermediate 2a′ in situ .…”

Quaternary α,α-2-Oxoazepane α-Amino Acids: Synthesis from Ornithine-Derived β-Lactams and Incorporation into Model Dipeptides

“…Oxidation of the 2-azetidinones 12 – 15 with K 2 S 2 O 8 /K 2 HPO 4 in CH 3 CN/H 2 O at 75 °C under bubbled Ar yielded the expected 1-unsubstituted analogues 16 – 19 in moderate yield (30–60%). No big differences were found in the oxidation of the 1-Pmb Orn derivative 12 and its Dmb analogue 13 ; therefore the Pmb group was selected, due to better yields in the cyclization to the β-lactam derivatives.…”

Synthetic turn mimetics and hairpin nucleators: Quo Vadimus?

“…57 It has been successful to a larger extent in imitating the topology of natural peptide components with improved binding and selectivity. Integrating constrained moieties witnessed the use of proline derivatives, 58 a-aminoxy acids, 59 g-turn inducing 2-alkyl-2carboxyazetidines, 60 b-lactam-derived amino acid, 61 and so on. To restrict the reverse turn architecture, one of the easiest ways is to integrate torsionally constrained amino acids into the peptide backbone.…”

Synthesis of tetracyclic dibenzo[ b , f ][1,4]oxazepine-fused β-lactams via visible-light-induced Staudinger annulation

“…According to previous studies, 8,9,11 a plausible reaction mechanism for this transformation is illustrated in Scheme 5. Firstly, visible light promoted Wolff rearrangement of α-diazo ketone 2a gives the ketene intermediate 2a′ in situ .…”

Quaternary α,α-2-Oxoazepane α-Amino Acids: Synthesis from Ornithine-Derived β-Lactams and Incorporation into Model Dipeptides

“…Oxidation of the 2-azetidinones 12 – 15 with K 2 S 2 O 8 /K 2 HPO 4 in CH 3 CN/H 2 O at 75 °C under bubbled Ar yielded the expected 1-unsubstituted analogues 16 – 19 in moderate yield (30–60%). No big differences were found in the oxidation of the 1-Pmb Orn derivative 12 and its Dmb analogue 13 ; therefore the Pmb group was selected, due to better yields in the cyclization to the β-lactam derivatives.…”

Synthetic turn mimetics and hairpin nucleators: Quo Vadimus?

“…57 It has been successful to a larger extent in imitating the topology of natural peptide components with improved binding and selectivity. Integrating constrained moieties witnessed the use of proline derivatives, 58 a-aminoxy acids, 59 g-turn inducing 2-alkyl-2carboxyazetidines, 60 b-lactam-derived amino acid, 61 and so on. To restrict the reverse turn architecture, one of the easiest ways is to integrate torsionally constrained amino acids into the peptide backbone.…”