Filip Bihelovic

Total Synthesis of (−)-atrop-Abyssomicin C†

In 2004, S ssmuth and co-workers reported the isolation of abyssomicin C, a naturally occurring antibiotic of exotic origin and complex structure. The mechanism of antibiotic activity of abyssomicin C against Gram-positive bacteria, including methycillinand vancomycin-resistant Staphylococcus aureus strains, was unprecedented: it inhibits tetrahydrofolate biosynthesis at an early stage. In addition to abyssomicin C, several other congeners have been found in both marine and terrestrial Streptomyces strains (Scheme 1). The combination of strong antibacterial activity

One-step, inexpensive high yield strategy for Candida antarctica lipase A isolation using hydroxyapatite

Lipase A from Candida antarctica (CAL A) was purified to apparent homogeneity in a single step using hydroxyapatite (HAP) chromatography. CAL A bound to HAP was eluted with 10mM Na-phosphate buffer, pH 7.0 containing 0.5% Triton X-100. The protocol resulted in a 3.74-fold purification with 94.7% final recovery and 400.83 U/mg specific activity. Silver staining after SDS-PAGE revealed the presence a single band of 45 kDa. The enzyme exhibited a temperature optimum of 60°C, was unaffected by monovalent metal ions, but was destabilized by divalent metal ions (Zn(2+), Ca(2+), Mg(2+), Cu(2+), Mn(2+)) and stimulated by 50mM Fe(2+). Detergents at 0.1% concentrations did not affect lipase activity. Except for Triton X-100, detergent concentrations of 1% had a destabilizing effect.

Gold(I)-Catalyzed Domino Cyclizations of Diynes for the Synthesis of Functionalized Cyclohexenone Derivatives. Total Synthesis of (−)-Gabosine H and (−)-6-epi-Gabosine H

1,6-Diynes with a t-butylcarbonate group in the propargylic position undergo gold(I)-catalyzed domino-cyclization which affords α-hydroxycyclohexenones. The described sequence can be applied on functionalized, highly oxygenated substrates, as examplified in the synthesis of (-)-gabosine H and its epimer.

Total Synthesis of (±)‐Alstoscholarisine A

The first total synthesis of the neuroactive indole alkaloid (±)-alstoscholarisine A is reported. The key step of the concise synthesis is an efficient domino sequence that was used to assemble the 2,8-diazabicyclo[3.3.1]nonane core through the formation of two C-N bonds and one C-C bond in a single step.

Study of the kinetic parameters for synthesis and hydrolysis of pharmacologically active salicin isomer catalyzed by baker’s yeast maltase

One of the key elements for understanding enzyme reactions is determination of its kinetic parameters. Since transglucosylation is kinetically controlled reaction, besides the reaction of synthesis, very important is the reaction of enzymatic hydrolysis of created product. Therefore, in this study, kinetic parameters for synthesis and secondary hydrolysis of pharmacologically active α isosalicin by baker’s yeast maltase were calculated, and it was shown that specifity of maltase for hydrolysis is approximately 150 times higher then for synthesis.

Synthesis of endoperoxides by domino reactions of ketones and molecular oxygen

Domino reactions of ketones with molecular oxygen in the presence of potassium hydroxide and potassium t-butoxide afford cyclic hydroperoxy acetals (3,5-dihydroxy-1,2-dioxanes). Mixed endoperoxides can also be obtained in a three-component reaction of two ketones and oxygen.