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.

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 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 B12 deficiency, however the cellular and molecular mechanisms underlying these effects remain unknown. The aim of this study was to examine the effect of vitamin B12 deficiency on melanocytes homeostasis. Hypocobalaminemia in vitro model was developed by treating epidermal melanocytes with synthesized vitamin B12 antagonist—hydroxycobalamin(c-lactam). The cells were examined using immunoenzymatic, spectrophotometric, and fluorimetric assays as well as image cytometry. Significant melanogenesis stimulation—the increase of relative melanin content and tyrosinase activity up to 131% and 135%, respectively—has been indicated. Cobalamin-deficient cells displayed the elevation (by 120%) in reactive oxygen species level. Moreover, the redox status imbalance was stated. The study provided a scientific evidence for melanocytes homeostasis disturbance under hypocobalaminemia, thus indicating a significant element of the hyperpigmentation mechanism due to vitamin B12 deficiency. Furthermore, the implication between pigmentary and hematological and/or neuropsychiatric symptoms in cobalamin-deficient patients may be an important issue.

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. It also reveals the presence of a hydrogen bond between the terminal hydroxy group and one of the axial cyanide ligands.

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 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 12 , 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.Letter pubs.acs.org/OrgLett

Herein, the synthesis of novel hydrophobic and hydrophilic cobinamides via aminolysis of vitamin B 12 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) 2 Cbi. Figure 1. Hydrophobic and hydrophilic cobinamides.Letter pubs.acs.org/acsmedchemlett