Vitamin B Deficiency Induces Imbalance in Melanocytes Homeostasis-A Cellular Basis of Hypocobalaminemia Pigmentary Manifestations.

Vitamin B deficiency causes significant changes in cellular metabolism leading to various clinical symptoms, such as hematological, psychiatric, and neurological disorders. We hypothesize that skin pigmentation disorders may be a diagnostically important manifestation of vitamin B deficiency, however the cellular and molecular mechanisms underlying these effects remain unknown. The aim of this study was to examine the effect of vitamin B deficiency on melanocytes homeostasis.

Vitamin B Catalyzed Atom Transfer Radical Addition.

Vitamin B, 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 B-Catalysis for Deprotection of (Allyloxy)arenes.

Vitamin B is a natural cobalt complex that, while reduced to the "supernucleophilic" Co(I) form, can easily react with electrophiles via an S2 mechanism. It is also shown to react via an S2' mechanism with allylic compounds allowing for photochemical deprotection of (allyloxy)arenes. A sustainable alternative to commonly used noble metal-catalyzed deprotection reactions is presented.

Vitamin B Catalysis: Probing the Structure/Efficacy Relationship.

Vitamin B is a cofactor for many enzymes, but it also functions as a catalyst in C-C bond-forming reactions. Herein, the impact of corrin structural modifications on their catalytic efficacy was examined. Derivatives with various substituents at c-, d-, and meso-positions were synthesised by using traditional and new microwave methodologies, and then tested in the model reaction of 1,1-diphenylethylene with ethyl diazoacetate.

Vitamin B12 Phosphate Conjugation and Its Effect on Binding to the Human B12 -Binding Proteins Intrinsic Factor and Haptocorrin.

The binding of vitamin B12 derivatives to human B12 transporter proteins is strongly influenced by the type and site of modification of the cobalamin original structure. We have prepared the first cobalamin derivative modified at the phosphate moiety. The reaction conditions were fully optimized and its limitations examined.

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.

Microwave-assisted cobinamide synthesis.

We present a new method for the preparation of cobinamide (CN)2Cbi, a vitamin B12 precursor, that should allow its broader utility. Treatment of vitamin B12 with only NaCN and heating in a microwave reactor affords (CN)2Cbi as the sole product. The purification procedure was greatly simplified, allowing for easy isolation of the product in 94% yield.

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.

Synthesis and evaluation of bifunctional sGC regulators: optimization of a connecting linker.

Hybrid molecules composed of PpIX and cobyrinic acid derivatives conjugated through linkers of varying length and composition were prepared via 1,3-dipolar cycloaddition (CuAAC) or amidation/esteryfication reactions. They were tested for activation of soluble guanylyl cyclase (sGC), a key enzyme in the NO/cGMP signaling pathway, by an in vitro GTP→cGMP conversion assay. Using purified heme-deficient sGC and truncated sGC variants lacking a heme-binding domain, we demonstrated that such hybrid molecules may activate sGC by targeting heme-binding and/or catalytic domain.

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.

Cobryketone derived from vitamin B12 via palladium-catalyzed cleavage of the sp3-sp3 carbon-carbon bond.

Heptamethyl cobyrinate was transformed into hexamethyl 8-nor-cobyrinate. The crucial step involved the synthesis of new, vitamin B12 derived cobryketone via palladium-catalyzed cleavage of the sp(3)-sp(3) carbon-carbon bond with the liberation of the ketone. The replacement of sp(3) carbon atom with sp(2) (C═O) at the 8-position produces a bathochromic shift of all absorption bands and makes α and β bands equal as a consequence of the expansion of the existing conjugated system of double bonds.

Protoporphyrin IX/Cobyrinate Derived Hybrids - Novel Activators of Soluble Guanylyl Cyclase.

A new cobyrinate/protoporphyrin IX molecular hybrids were prepared via CuAAC reaction. The synthesis involved selective preparation of cobyrinate and PpIX derived building blocks possessing respectively terminal alkyne and azide moieties followed by the CuOAc catalyzed cycloaddition reaction. Synthesized molecules activated soluble guanylyl cyclase showing strong linker length/activation dependence.

Vitamin B₁₂ derivatives as activators of soluble guanylyl cyclase.

Various newly prepared and previously known vitamin B₁₂ derivatives have been studied as potential soluble guanylyl cyclase (sGC) activators. All compounds tested were found to activate the sGC enzyme, although to differing extents. The best results were obtained with the derivatives synthesized from c-lactone and possessing aliphatic amides in the c- and d-positions.

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.

New hydrophobic vitamin B12 derivatives via ring-opening reactions of c-lactone.

A selective synthesis of new hydrophobic cobalamin derivatives bearing two different spacers has been accomplished via ring-opening reaction of c-lactone. The reaction of c-lactone with various amines afforded three types of amides (a, b, and c) depending on the reaction conditions. The structure of lactone b was determined by the X-ray analysis confirming the position of ring closure.