A study towards the synthesis of (-)-atrop-abyssomicin C core

An attempt to synthesize the cyclohexane core of antibiotic abyssomicin C is described. The initial, protecting group-free approach (relying on internal protection) failed and had to be modified, in order to allow for efficient deprotection of the acid-sensitive cyclization precursor in the penultimate synthetic step. Thus, a pyranoside structural unit was used as a latent lactone/ester functionality, which was deprotected via thioacetalization/hydrolysis/oxidation sequence, to give the δ-valerolactone-type cyclization precursor. Unfortunately, the key cyclization reaction was not feasible, even after structural modification of the cyclization precursor. Reluctance towards cyclization turned out to be a general property of (at least some) Δ7-unsaturated esters, which required the development of a new strategy for this type of transformation

Supplementary data for the article: Vulovic, B.; Trmcic, M.; Matovic, R.; Saicic, R. N. Cyclization Reactions of Oxyallyl Cation. A Method for Cyclopentane Ring Formation. Organic Letters 2019, 21 (23), 9618–9621. https://doi.org/10.1021/acs.orglett.9b03791

Supplementary material for: [ https://doi.org/10.1021/acs.orglett.9b03791]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/3819

Supplementary data for the article: Vulovic, B.; Trmcic, M.; Matovic, R.; Saicic, R. N. Cyclization Reactions of Oxyallyl Cation. A Method for Cyclopentane Ring Formation. Organic Letters 2019, 21 (23), 9618–9621. https://doi.org/10.1021/acs.orglett.9b03791

Supplementary material for: [ https://doi.org/10.1021/acs.orglett.9b03791]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/3819

Supplementary data for article: Novkovic, L.; Trmcic, M.; Rodic, M.; Bihelovic, F.; Zlatar, M.; Matovic, R.; Saicic, R. N. Synthesis of Endoperoxides by Domino Reactions of Ketones and Molecular Oxygen. RSC Advances 2015, 5 (120), 99577–99584. https://doi.org/10.1039/c5ra13476e

Supplementary material for: [https://doi.org/10.1039/c5ra13476e]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2000

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.Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3442

Supplementary data for article:Trmčić, M.; Matović, R. V.; Tovilović, G.; Ristic, B. Z.; Trajković, V. S.; Ferjančić, Z.; Saičić, R. A Novel C,D-Spirolactone Analogue of Paclitaxel: Autophagy Instead of Apoptosis as a Previously Unknown Mechanism of Cytotoxic Action for Taxoids. Organic and Biomolecular Chemistry 2012, 10 (25), 4933–4942. https://doi.org/10.1039/c2ob25514f

Supplementary material for: [https://doi.org/10.1039/c2ob25514f]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1304

Supplementary data for article: Novkovic, L.; Trmcic, M.; Rodic, M.; Bihelovic, F.; Zlatar, M.; Matovic, R.; Saicic, R. N. Synthesis of Endoperoxides by Domino Reactions of Ketones and Molecular Oxygen. RSC Advances 2015, 5 (120), 99577–99584. https://doi.org/10.1039/c5ra13476e

Supplementary material for: [https://doi.org/10.1039/c5ra13476e]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2000

Supplementary data for article: Trmčić, M.; Chadbourne, F. L.; Brear, P. M.; Denny, P. W.; Cobb, S. L.; Hodgson, D. R. W. Aqueous Synthesis of N,S-Dialkylthiophosphoramidates: Design, Optimisation and Application to Library Construction and Antileishmanial Testing. Organic and Biomolecular Chemistry 2013, 11 (16), 2660–2675. https://doi.org/10.1039/c3ob27448a

Supplementary material for: [https://doi.org/10.1039/c3ob27448a]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1620]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/2821

Development of iminosugar-based glycosidase inhibitors as drug candidates for SARS-CoV-2 virus via molecular modelling and in vitro studies

We developed new iminosugar-based glycosidase inhibitors against SARS-CoV-2. Known drugs (miglustat, migalastat, miglitol, and swainsonine) were chosen as lead compounds to develop three classes of glycosidase inhibitors (α-glucosidase, α-galactosidase, and mannosidase). Molecular modelling of the lead compounds, synthesis of the compounds with the highest docking scores, enzyme inhibition tests, and in vitro antiviral assays afforded rationally designed inhibitors. Two highly active α-glucosidase inhibitors were discovered, where one of them is the most potent iminosugar-based anti-SARS-CoV-2 agent to date (EC90 = 1.94 µM in A549-ACE2 cells against Omicron BA.1 strain). However, galactosidase inhibitors did not exhibit antiviral activity, whereas mannosidase inhibitors were both active and cytotoxic. As our iminosugar-based drug candidates act by a host-directed mechanism, they should be more resilient to drug resistance. Moreover, this strategy could be extended to identify potential drug candidates for other viral infections

Cyclization Reactions of Oxyallyl Cation. A Method for Cyclopentane Ring Formation

Unsaturated oxyallyl cations with a suitably positioned alkene bond undergo 5-exo-cyclization with the formation of vinylcyclopentane derivatives. Alkyne analogues provide allenes. The reaction proceeds with a moderate to excellent level of stereoselectivity and allows for asymmetric induction in the reaction with chiral substrate.Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3841