Diastereoselective Synthesis of (3R,5R)-γ-Hydroxypiperazic Acid

We report an asymmetric synthesis of the (3R,5R)-γ-hydroxypiperazic acid (γ-OHPiz) residue encountered in several bioactive nonribosomal peptides. Our strategy relies on a diastereoselective enolate hydroxylation reaction and electrophilic N-amination to provide the acyclic γ-OHPiz precursor. This orthogonally protected α-hydrazino acid intermediate is amenable to late-stage diazinane ring formation following incorporation into a peptide chain. We determined the N-terminal amide rotamer propensity of the γ-OHPiz residue and showed that the γ-OH substituent enhances trans-amide bias relative to piperazic acid.

A tautomeric ligand enables directed C‒H hydroxylation with molecular oxygen

Hydroxylation of aryl carbon–hydrogen bonds with transition metal catalysts has proven challenging when oxygen is used as the oxidant. Here, we report a palladium complex bearing a bidentate pyridine/pyridone ligand that efficiently catalyzes this reaction at ring positions adjacent to carboxylic acids. Infrared, x-ray, and computational analysis support a possible role of ligand tautomerization from mono-anionic (L,X) to neutral (L,L) coordination in the catalytic cycle of aerobic carbon–hydrogen hydroxylation reaction. The conventional site selectivity dictated by heterocycles is overturned by this catalyst, thus allowing late-stage modification of compounds of pharmaceutical interest at previously inaccessible sites.

Photocatalytic hydroxylation of benzene to phenol over organosilane-functionalized FeVO4 nanorods

Photocatalytic benzene hydroxylation reaction using clean oxidant such as H2O2 is a green synthetic approach for phenol synthesis. Here, our study shows that the silylated iron vanadate (FeVO4) nanorods can...

μ-Oxo-bridged diiron(iii) complexes of tripodal 4N ligands as catalysts for alkane hydroxylation reaction using m-CPBA as an oxidant: substrate vs. self hydroxylation

The ligand stereoelectronic effect of diiron(iii) complexes determines the efficiency and selectivity of catalytic alkane hydroxylation with m-CPBA as an oxidant.

Biotechnological Transformation of Hydrocortisone into 16α-Hydroxyprednisolone by Coupling Arthrobacter simplex and Streptomyces roseochromogenes

16α-Hydroxyprednisolone, an anti-inflammatory drug, could be potentially obtained from hydrocortisone bioconversion by combining a 1,2-dehydrogenation reaction performed by Arthrobacter simplexATCC31652 with a 16α-hydroxylation reaction by Streptomyces roseochromogenes ATCC13400. In this study we tested, for the first time, potential approaches to couple the two reactions using similar pH and temperature conditions for hydrocortisone bioconversion by the two strains. The A. simplex capability to 1,2-dehydrogenate the 16α-hydroxyhydrocortisone, the product of S. roseochromogenes transformation of hydrocortisone, and vice versa the capability of S. roseochromogenes to 16α-hydroxylate the prednisolone were assessed. Bioconversions were studied in shake flasks and strain morphology changes were observed by SEM. Whole cell experiments were set up to perform the two reactions in a sequential mode in alternate order or contemporarily at diverse temperature conditions. A. simplex catalyzed either the dehydrogenation of hydrocortisone into prednisolone efficiently or of 16α-hydroxyhydrocortisone into 16α-hydroxyprednisolone in 24 h (up to 93.9%). Surprisingly S. roseochromogenes partially converted prednisolone back to hydrocortisone. A 68.8% maximum of 16α-hydroxyprednisolone was obtained in 120-h bioconversion by coupling whole cells of the two strains at pH 6.0 and 26 °C. High bioconversion of hydrocortisone into 16α-hydroxyprednisolone was obtained for the first time by coupling A. simplex and S. roseochromogenes.

On the Ability of Nickel Complexes Derived from Tripodal Aminopyridine Ligands to Catalyze Arene Hydroxylations

The development of catalysts for the selective hydroxylation of aromatic C–H bonds is an essential challenge in current chemical research. The accomplishment of this goal requires the discovery of powerful metal-based oxidizing species capable of hydroxylating inert aromatic bonds in a selective manner, avoiding the generation of non-selective oxygen-centered radicals. Herein we show an investigation on the ability of nickel(ii) complexes supported by tripodal tetradentate aminopyridine ligands to catalyze the direct hydroxylation of benzene to phenol with H2O2 as oxidant. We have found that modifications on the ligand structure of the nickel complex do not translate into different reactivity, which differs from previous findings for nickel-based arene hydroxylations. Besides, several nickel(ii) salts have been found to be effective in the oxidation of aromatic C–H bonds. The use of fluorinated alcohols as solvent has been found to result in an increase in phenol yield; however, showing no more than two turn-overs per nickel. These findings raise questions on the nature of the oxidizing species responsible for the arene hydroxylation reaction.