Maksymilian Karczewski

V-Shaped Bis-Coumarins: Synthesis and Optical Properties

A highly efficient procedure for the synthesis of bis-coumarins fused at the pyranone ring has been developed. The electron-rich phenols reacted with esters of coumarin-3-carboxylic acids, leading to substituted chromeno[3,4-c]chromene-6,7-diones. The reaction is catalyzed by both Lewis acids and 4-dimethylaminopyridine. The most probable mechanistic pathway involves Lewis acid catalyzed or DMAP catalyzed transesterification, followed by intramolecular conjugate addition of α,β-unsaturated esters to phenols and subsequent oxidation of the initially formed intermediate. The reaction is compatible with various functionalities such as NO2, Br, and OMe. Not only benzene derivatives but also dihydroxynaphthalenes are reactive in this reaction, and the structure of the product can be controlled by adjusting the reaction conditions. Furthermore, a double addition is possible, leading to a horseshoe-shaped system comprised of seven conjugated rings. Compounds with four structurally unique skeletons have been obtained and have been shown to strongly absorb in the violet, blue, and/or green regions of the visible spectrum. Most of them display strong greenish yellow fluorescence, which can be modulated by both structural changes and the character of the solvents. Again, introduction of an electron-donating group in the chromeno[3,4-c]chromene-6,7-diones caused a significant red shift in both the absorption and emission maxima, and the effect became especially noteworthy in the case of amino substituents.

Porphyrins as substrates in CuAAC — exclusion of unwanted copper insertion into the macrocyclic core

Unwanted copper insertion into a free base porphyrin starting material during Cu-catalyzed [1,3] azide-alkyne dipolar cycloaddition (CuAAC) is not observed when using (1,10-phenanthroline)-bis(triphenylphosphine)copper(I) nitrate as a catalyst. Reactions give 1,4-disubstituted 1,2,3-triazoles in good yields for a broad range of porphyrins. 1,5-Disubstituted 1,2,3-triazole cycloadducts can be generated in the presence of Cp*RuCl(COD).

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. The use of microwave heating proved beneficial also for (CN)2Cbi(c-lactone) synthesis. Treatment of (CN)2Cbi with triethanolamine led to (CN)2Cbi(c-lactam).

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. While all conjugates activated sGC, only selected compounds served as bifunctional regulators and were capable of simultaneous targeting both heme and catalytic domains of sGC. The length and type of a linker connecting both components had a profound effect on the extent of sGC activation, indicating that the linkers type is crucial for their binding affinities with regulatory and catalytic domains. Only hybrids with the conjugated linker of 13-16 atom length synergistically target both domains and displayed the lowest EC50 and highest activating potency. Compounds with shorter connecting linkers were much less potent and were no more active than the cobyrinic acid component alone. The most active conjugate, which showed a 60-fold activation of sGC, was compound 11, in which PpIX and cobyrinic acid components are separated by 11 atoms chain with the triazole moiety in between.

Vitamin B12 Catalysis: Probing the Structure/Efficacy Relationship

Vitamin B12 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. To complement the experimental data, cyclic voltammetry and DFT calculations were performed. Mainly alterations at the c- or d-positions influence both the reaction yield and selectivity.

meso-Modified Cobalamins: Synthesis, Structure, and Properties

Vitamin B12 and its derivatives present excellent paradigms for bioinspired catalysis. The inherent challenges for derivatizing cobalamins, such as vitamin B12 , to incorporate them in supramolecular designs and materials, limit the range of their utility and applications. Herein, we present a synthetic approach toward derivatives of vitamin B12 possessing electron-donating and -withdrawing substituents at the meso position (C10). Spectroscopic and cyclic voltammetry studies reveal that changes in the substitution pattern on the equatorial ligand have a significant impact on the electronic and optical properties of the cobalamin. These synthetic methods, therefore, provide invaluable routes not only for covalent linking to other structures, but also for attaining a wide range of functionalities for the derivatives of vitamin B12 .