Adam Janczuk

Aqueous Baylis–Hillman reactions of cyclopent-2-enone using imidazole as catalyst

Abstract In aqueous media, imidazole was found to catalyse Baylis–Hillman reactions of cyclopent-2-enone with various aldehydes to afford the desired adducts with high yields.

NO donors with anticancer activity

Nitric oxide (NO) radicals, endogenously produced from L-arginine or supplied by NO-releasing donors, are involved in numerous physiological and pathological processes. Although there has been rapid growth in NO research, cancer research still remains in its infancy. A few reports suggest that NO has some anticancer properties, yet others implicate NO in tumour promotion. This article will focus on the anticancer activity of NO donors that have been claimed in patents between 1998 and 2001.

Chemo-enzymatic synthesis of polyhydroxyazepanes

Abstract Galactose oxidase (EC 1.1.3.9, GAO) is an extracellular copper-containing enzyme that utilizes molecular oxygen to convert the C6-primary hydroxyl moiety of d -galactopyranosides to hydrated aldehydes. Subsequent dehydratative coupling with hydroxylamines produces oximes ( 3a – f ), which, when subjected to conditions of hydrogenolysis, give rise to polyhydroxyazepanes ( 11 – 17 ).

Ytterbium triflate catalyzed electrophilic substitution of indoles: the synthesis of unnatural tryptophan derivatives

Abstract Benzylamine was combined with ethyl glyoxylate to form the intermediate imine which in the presence of catalytic amount of Yb(OTf) 3 underwent electrophilic substitution on the 3-position of a variety of indoles to produce unnatural tryptophan derivatives. Penicillin-G-acylase mediated N -acylation produced optically active tryptophan derivatives.

The synthesis of deoxy-α-Gal epitope derivatives for the evaluation of an anti-α-Gal antibody binding

Abstract α-Gal epitopes (also termed as α-Gal) are carbohydrate structures bearing the α- d -Gal-(1→3)-β- d -Gal terminus 1 and are known to be the antigen responsible for antibody-mediated hyperacute rejection in xenotransplantation. Terminal 2-, 3-, 4-, and 6-deoxy-Gal derivatives of α-Gal were synthesized. Inhibition ELISA using mouse laminin was established to determine the binding affinity of the synthesized α-Gal derivatives. 4-Deoxy-α-Gal derivative 7 showed a significant reduction in antibody recognition. The IC 50 value was 15-fold poorer than the standard α-Gal epitopes α- d -Gal-(1→3)-β- d -Gal-(1→4)-β- d -Glc-NHAc ( 39 ) and α- d -Gal-(1→3)-β- d -Gal-(1→4)-β- d -Glc-OBn ( 40 ). A similar observation was seen with 2-deoxy-α-Gal derivative 5 , whose IC 50 value was nearly tenfold higher than the standards. Interestingly, substitution at the terminal 3-position resulted in only a fourfold decrease in antibody recognition, suggesting a possible point of future derivation. Finally, 6-deoxy-α-Gal derivative 8 exhibited similar antibody recognition to both α-Gal epitope 39 and α-Gal epitope 40 . This strongly suggests that derivatization at the 6-position can be accomplished without loss of antibody recognition. These findings can be utilized for the future design of other α-Gal derivatives.

Expeditious syntheses of two carbohydrate-linked cisplatin analogs

The syntheses of two carbohydrate-linked cisplatin analogs, namely lacto- and alpha-Gal-cisplatin, are described. A fusion enzymatic approach was used to create the diazido-alpha-Gal trisaccharide intermediate in the synthesis of alpha-Gal-cisplatin.

Ytterbium(III) triflate-catalyzed electrophilic cyclization of glyoxalate-derived unsaturated imines

Ytterbium(III) triflate was found to catalyze the electrophilic cyclization of some glyoxalate-derived unsaturated imines. The cyclization reactions gave exclusively fused amino γ-lactone products with good stereoselectivity. Moreover, a solid-phase version of the lanthanide-catalyzed reaction featured a lactonization with simultaneous cleavage of the product from the solid support.

Alpha-Galactosyl trisaccharide epitope: Modification of the 6-primary positions and recognition by human anti-αGal antibody

Galactose oxidase (EC 1.1.3.9, GAO) was used to convert the C-6′ OH of Galβ(1 → 4)Glcβ–OBn (5) to the corresponding hydrated aldehyde (7). Chemical modification, through dehydratative coupling and reductive amination, gave rise to a small library of Galβ(1 → 4)Glcβ–OBn analogues (9a–f, 10, 11). UDP-[6-3H]Gal studies indicated that α1,3-galactosyltransferase recognized the C-6′ modified Galβ(1 → 4)Glcβ–OBn analogues (9a–f, 10, 11). Preparative scale reactions ensued, utilizing a single enzyme UDP-Gal conversion as well as a dual enzymatic system (GalE and α1,3GalT), taking full advantage of the more economical UDP-Glc, giving rise to compounds 6, 15–22. Galα(1 → 3)Galβ(1 → 4)Glcβ–OBn trisaccharide (6) was produced on a large scale (2 g) and subjected to the same chemoenzymatic modification as stated above to produce C-6″ modified derivatives (23–30). An ELISA bioassay was performed utilizing human anti-αGal antibodies to study the binding affinity of the derivatized epitopes (6, 15–30). Modifications made at the C-6′ position did not alter the IgG antibodys ability to recognize the unnatural epitopes. Modifications made at the C-6″ position resulted in significant or complete abrogation of recognition. The results indicate that the C-6′ OH of the αGal trisaccharide epitope is not mandatory for antibody recognition. Published in 2004.

Recent progress in lanthanide-catalyzed organic reactions in protic media

Lanthanide triflates are stable in water. It is possible for lanthanides to undergo many organic reactions in environmentally friendly solvents. This makes lanthanides very promising in the field of green chemistry. This review describes the recent development of the lanthanidecatalyzed organic reactions in protic solvents. Those reactions include Diels-Alder, Aldol, Allylation, acetalization, pericyclization, radical reactions as well as some newlydeveloped lanthnidesbased catalysts.

O-Alkylation chemistry of neocupferron

Abstract O -Alkylation of N -hydroxy- N -nitroso-1-naphthalenamine ammonium salt (neocupferron) leads to two isomers, (1,4) naphthoquinone O -alkyl oxime oxime ( A ) and N -alkyloxy- N ′ - naphthyldiimide N ′-oxide ( B ). Characterization was done by 1 H, 13 C NMR and X-ray analysis. These derivatives showed increased stability compared to their parent compound, neocupferron, in the ability to release nitric oxide (NO). Some of these O -alkyl derivatives can be novel photo-releasing NO compounds.