Synthesis of a Non-Heme Template for Attaching Four Peptides:  An Approach to Artificial Iron(II)-Containing Peroxidases

Abstract

We are developing all-synthetic model cofactor-protein complexes in order to define the parameters controlling non-natural cofactor activity. The long-term objective is to establish the theoretical and practical basis for designing novel enzymes. A non-heme pentadentate ligand (N4Py) is being developed as a template for the site-specific attachment of a designed four-helix bundle. Previously, we attached two unprotected peptides via CH(2)Cl handles to N4Py. In the presence of hydrogen peroxide, the iron(II) complex of this ligand (2a) generates an Fe(III)OOH intermediate (3a) that can oxidize a wide variety of organic compounds. Here, we describe the synthesis of 27, a N4Py derivative in which four three-carbon spacers have been introduced, and show that four copies of an unprotected, single-cysteine peptide can be coupled via a thioether linkage to the ligand. In addition, a divergent synthesis route to tetrabromide ligand 1b has also been developed, providing the opportunity to prepare alternative pentadentate ligands efficiently by four cross-coupling reactions on a single molecule. Also, two of the four bromides of 1b can be selectively addressed by magnesium-bromide exchange.

Supported palladium catalysis using a heteroleptic 2-methylthiomethylpyridine–N,S–donor motif for Mizoroki–Heck and Suzuki–Miyaura coupling, including continuous organic monolith in capillary microscale flow-through mode

“…PdCl 2 (NCMe) 2 under identical conditions, matching that for the synthesis of PdCl 2 (L 1 ) (8) and PdCl 2 (L 2 ) (9). A scanning electron micrograph of bulk monolith after attachment of ligand and palladium (Fig.…”

“…Subsequently, the systems were treated with (8), 2.037(3); S1 2.247(3), 2.2617 (9); Cl1 (trans to S1) 2.321(3), 2.3305 (9); Cl2 (trans to N1) 2.299(3), 2.2967(10) Å, for 8 and 9, respectively] and chelate angles [84.5(2) , 84.58 (6) ] are similar to values reported for related Pd(II) complexes. 14 The pyridyl mean plane forms a dihedral angle of 16.2(4) (8) and 18.9(1) (9) with the mean metal coordination plane, the aryl/pyridyl inter-ring dihedral angles are 8.1(7) (8) and 19.8(2) (9), and the C-O and inter-ring C-C distances of both 8 and 9 are within 1 esd of those for ligand 6.…”

Donor‐Acceptor Substituted 2‐Phenylpyridines by Means of Reductive C,C–Cross Coupling Reaction

“…The synthesis of the aryl bromides 1 a , 1 b , 1 c and 1 d , the aryl iodides 1 e , 1 f and 1 g , 2‐Bromopyridine‐5‐carbaldehyde ( 2 h ) and the acetals ( 2 d, 2 g ) [17] was performed as described in literature.…”

Human carbonic anhydrase II as host protein for the creation of artificial metalloenzymes: the asymmetric transfer hydrogenation of imines

“…Its synthesis was based on key steps starting from a Boekelheide reaction 28,29 and followed by an oxidation to the corresponding aldehyde. 30 Treatment with hydroxylamine hydrochloride yielded the oxime 17.…”