Efficient synthesis of hydrocarbon-bridged diaminodiacids through nickel-catalyzed reductive cross-coupling

Synthesis and applications of symmetric amino acid derivatives

“…Metal-catalysed cross-coupling reactions of amino acid derivatives are powerful synthetic methods that can be used to synthesize more diverse bis-amino acid derivatives. The Negishi reaction, 13 Sonogashira reaction, 14 Suzuki–Miyaura coupling reaction, 15 copper-catalysed alkyne dimerization, 16 and nickel-catalysed reductive dimerization 17 have been reported (Scheme 2). Metal-catalysed cross-coupling reactions were utilized for the total synthesis of the tetrasubstituted pyridinium amino acid (+)-desmosine, which is a cross-linker of elastin (Scheme 3).…”

A Diaminodiacid (DADA) Strategy for the Development of Disulfide Surrogate Peptides

“…A nickel catalyzed reductive crosscoupling reaction was recently reported for the preparation of Dmab/ivDde protected diaminodiacids incorporating hydrocarbon bridges (8, Figure 4). [15] The synthesis began with the preparation of benzyl (Bn)/benzyloxycarbonyl (Cbz) protected homo-Ser bromides and tert-butyl (tBu)/tert-butoxycarbonyl (Boc) protected homo-Ser bromides. With two orthogonally protected homoserine bromides in hand, the key hydrocarbon bridge was constructed by nickel-catalyzed cross-coupling method using bis(pinacolato)diboron as reducing reagent.…”

Bridged bicyclic peptides: Structure and function

“…For example, the alkyl linked bicyclic peptide TPI‐2 ( 77 ) was prepared (Scheme ) incorporating diaminosuberic acid residues in place of the cystines in the analogous disulfide‐containing peptide tachyplesin I (TPI‐1). TPI‐1 is a 17‐residue bicyclic peptide with high antimicrobial activity . The alkyl‐linked TPI‐2 77 displayed similar antimicrobial activity to TPI‐1 yet was stable to dithiothreitol treatment, whereas disulfide‐linked TPI‐1 was completely reduced within 1 h. Further, TPI‐2 77 was stable in serum (85% remaining after 24 h).…”