Cobalt Catalyst Determines Regioselectivity in Ring Opening of Epoxides with Aryl Halides.

Ring-opening of epoxides furnishing either linear or branched products belongs to the group of classic transformations in organic synthesis. However, the regioselective cross-electrophile coupling of aryl epoxides with aryl halides still represents a key challenge. Herein, we report that the vitamin B12/Ni dual-catalytic system allows for the selective synthesis of linear products under blue-light irradiation, thus complementing methodologies that give access to branched alcohols. Experimental and theoretical studies corroborate the proposed mechanism involving alkylcobalamin as an intermediate in this reaction.

Minisci C-H Alkylation of Heteroarenes Enabled by Dual Photoredox/Bromide Catalysis in Micellar Solutions*.

Aromatic heterocycles are omnipresent structural motifs in various natural products, pharmaceuticals and agrochemicals. This work describes a photocatalytic Minisci-type C-H functionalization of heteroarenes with non-activated alkyl bromides. The reaction avoids stoichiometric radical-promoters, oxidants, or acids, and is conducted using blue LEDs as the light source. The reactive carbon-centered alkyl radicals are generated by merging the photoredox approach with bromide anion co-catalysis and spatial pre-aggregation of reacting species in the micellar aqueous solutions. The obtained data highlight the critical importance of microstructuring and organization of the components in the reaction mixture.

Vitamin B12 transports modified RNA into E. coli and S. Typhimurium cells.

Specifically designed, antisense oligonucleotides are promising candidates for antibacterial drugs. They suppress the correct expression of bacterial genes by complementary binding to essential sequences of bacterial DNA or RNA. The main obstacle in fully utilizing their potential as therapeutic agents comes from the fact that bacteria do not uptake oligonucleotides from their environment. Herein, we report that vitamin B12 can transport oligonucleotides into Escherichia coli and Salmonella typhimurium cells. 5'-Aminocobalamin with an alkyne linker and azide-modified oligonucleotides enabled the synthesis of vitamin B12-2'OMeRNA conjugates using an efficient "click" methodology. Inhibition of protein expression in E. coli and S. Typhimurium cells indicates an unprecedented transport of 2'OMeRNA oligomers into bacterial cells via the vitamin B12 delivery pathway.

Vitamin B12 Catalyzed Atom Transfer Radical Addition.

Vitamin B12, a natural Co-complex, catalyzes atom transfer radical addition (ATRA) of organic halides to olefins. The established conditions were found to be very selective, with atom transfer radical polymerization (ATRP) occurring only in the case of acrylates.

Photoinduced Vitamin B12-Catalysis for Deprotection of (Allyloxy)arenes.

Vitamin B12 is a natural cobalt complex that, while reduced to the "supernucleophilic" Co(I) form, can easily react with electrophiles via an SN2 mechanism. It is also shown to react via an SN2' mechanism with allylic compounds allowing for photochemical deprotection of (allyloxy)arenes. A sustainable alternative to commonly used noble metal-catalyzed deprotection reactions is presented.

Cobalt(i)-catalysed CH-alkylation of terminal olefins, and beyond.

Cobalester, a natural nontoxic vitamin B12 derivative, was found to catalyse unusual olefinic sp(2) C-H alkylation with diazo reagents as a carbene source instead of the expected cyclopropanation.

Vitamin B12 catalysed reactions.

Vitamin B12 (cobalamin, 1) is one of a few naturally occurring organometallic molecules. As a cofactor for adenosylcobalamin-dependent and methylcobalamin-dependent enzymes, it plays a crucial role in biological processes, including DNA synthesis and regulation, nervous system function, red blood cell formation, etc. Enzymatic reactions, such as isomerisation, dehalogenation, and methyl transfer, rely on the formation and cleavage of the Co-C bond. Because it is a natural, nontoxic, environmentally benign cobalt complex, cobalamin (1) has been successfully utilised in organic synthesis as a catalyst for Co-mediated reactions. This tutorial review concisely describes cobalamin-catalysed organic reactions that hold promise for environmentally friendly cobalt catalysis, leaving the reader with basic knowledge and the ability to harness the catalytic potential of this fascinating molecule.

Small alterations in cobinamide structure considerably influence sGC activation.

Specially designed B-ring-modified cobalamin derivatives were synthesized and tested as potential activators of soluble guanylyl cyclase (sGC). Herein, we disclose the influence of substituents at the c- and d-positions in hydrophilic and hydrophobic cobyrinic acid derivatives on their capacities to activate sGC. The presence of the amide group at c-/d-position in cobyrinic acid derivatives strongly influence the level of sGC activation. Removal of the d-position altogether has a profound effect for hydrophobic compounds. In contrast, little differences were observed in hydrophilic ones.

Vitamin B12: chemical modifications.

Vitamin B12 plays a key role in many metabolic processes occurring in all mammals. Over the years its biological role has been extensively studied generating a lot of interest in the chemistry of this vital molecule. This established a variety of new methodologies for the synthesis and analysis of new cobalamin derivatives as well as creative purification techniques. This tutorial review summarizes all the advancements made in this area, providing a deeper insight into vitamin B12 chemistry.

Synthesis of New Hydrophilic and Hydrophobic Cobinamides as NO-Independent sGC Activators.

Herein, the synthesis of novel hydrophobic and hydrophilic cobinamides via aminolysis of vitamin B12 derivatives that activate soluble guanyl cyclase (sGC) is presented. Unlike other sGC regulators, they target the catalytic domain of sGC and show higher activity than (CN)2Cbi.

Selective modifications of hydrophobic vitamin B12 derivatives at c-and d-positions.

The acid-sensitivity of vitamin B(12) derived mono- and diamides was studied. It was found that the use of reductive ring-opening of the lactone moiety deactivated undesired decomposition of c-mono- and c,d-diamides under acidic conditions. As a result, reactions gave respectively c- or d-acids which were further functionalized via coupling with amino acids. Though mono- and diamides exhibited acid sensitivity, they were used for the preparation of several highly functionalized molecules showing their stability under various reaction conditions.