Use of the Mitsunobu Reaction in the Synthesis of Orthogonally Protected a,b-Diaminopropionic Acids

Orthogonally protected a,b-diaminopropionic acids have been synthesised in good yields by the reaction of N-trityl L-serine esters with N-substituted sulfonamides under Mitsunobu reaction conditions (DEAD, PPh3, THF). The best isolated yields were obtained when N-Boc p-toluenesulfonamide was used as the nitrogen nucleophile precursor in the Mitsunobu reaction. Subsequently, the N-trityl group was efficiently replaced with the more stable allyloxycarbonyl (alloc) group

Studies on the Synthesis of Orthogonally Protected Azalanthionines, and of Routes towards b-Methyl Azalanthionines, by Ring-Opening of N-Activated Aziridine-2-Crboxylates

Orthogonally protected azalanthionines were successfully synthesised by the ring-opening of N-activated aziridine-2-carboxylates with protected diaminopropanoic acids (DAPs). The required DAPs were also prepared by ring-opening of N-activated aziridine-2-carboxylates with para-methoxybenzylamine, but it was found that the choice of aziridine protecting groups dictated both the success of the reaction as well as the regioselectivity of the isolated products. Attempts to extend the methodology to the preparation of the more sterically demanding b-methyl azalanthionines have, so far, been unsuccessful

Synthesis of Orthogonally Protected Azalanthionines (Lanazanines) by Sequential Ring-Opening of N-Substituted Aziridine 2-Carboxylates

Orthogonally protected azalanthionines (lanazanines, 4-azadiaminopimelic acids or b-aminoalaninoalanines) have been synthesised in good yields by the ring-opening of N-protected aziridine 2-carboxylates with suitably protected diaminopropanoic acids (DAPs). The required DAPs were also synthesised by ring-opening of N-protected aziridine 2-carboxylates with para-methoxybenzylamine

Solid-Phase Peptide Synthesis of Analogues of the N-Terminus A-ring Fragment of the Lantibiotic Nisin: Replacements for the Dehydroalanine (Dha) Residue at Position 5 and the First Incorporation of a Thioamide Residue

A number of A-ring analogues of the lantibiotic nisin, containing replacements for the Dha at position 5, have been successfully prepared by solid-phase peptide synthesis. The Dha replacements include glycine, alanine, phenylalanine, serine and 1-aminocyclopropyl carboxylic acid (ACCa). The incorporation of a thioamide-isoleucine residue at position 4 is also described and is the first report of the preparation of a lantibiotic ring fragment containing a thioamide link

Synthesis of orthogonally protected azalanthionines (lanazanines) by sequential ring-opening of N-substituted aziridine 2-carboxylates

Orthogonally protected azalanthionines (lanazanines, 4-azadiaminopimelic acids or beta-aminoalaninoalanines) have been synthesised in good yields by the ring-opening of N-protected aziridine 2-carboxylates with suitably protected diaminopropanoic acids (DAPs). The required DAPs were also synthesised by ring-opening of N-protected aziridine 2-carboxylates with para-methoxybenzylamine. (C) 2013 Elsevier Ltd. All rights reserved

Studies on the synthesis of orthogonally protected azalanthionines, and of routes towards beta-methyl azalanthionines, by ring opening of N-activated aziridine-2-carboxylates

Orthogonally protected azalanthionines were successfully synthesised by the ring-opening of N-activated aziridine-2-carboxylates with protected diaminopropanoic acids (DAPs). The required DAPs were also prepared by ring-opening of N-activated aziridine-2-carboxylates with para-methoxybenzylamine, but it was found that the choice of aziridine protecting groups dictated both the success of the reaction as well as the regioselectivity of the isolated products. Attempts to extend the methodology to the preparation of the more sterically demanding beta-methyl azalanthionines have, so far, been unsuccessful. (C) 2014 Elsevier Ltd. All rights reserved

Cobryketone Derived from Vitamin B₁₂ <i>via</i> Palladium-Catalyzed Cleavage of the sp³–sp³ Carbon–Carbon Bond

Heptamethyl cobyrinate was transformed into hexamethyl 8-<i>nor</i>-cobyrinate. The crucial step involved the synthesis of new, vitamin B₁₂ derived cobryketone <i>via</i> palladium-catalyzed cleavage of the sp³–sp³ carbon–carbon bond with the liberation of the ketone. The replacement of sp³ carbon atom with sp² (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

Vitamin B12 Deficiency Induces Imbalance in Melanocytes Homeostasis—A Cellular Basis of Hypocobalaminemia Pigmentary Manifestations

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&mdash;hydroxycobalamin(c-lactam). The cells were examined using immunoenzymatic, spectrophotometric, and fluorimetric assays as well as image cytometry. Significant melanogenesis stimulation&mdash;the increase of relative melanin content and tyrosinase activity up to 131% and 135%, respectively&mdash;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

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

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