Sintetičke studije analoga paklitaksela sa modifikovanim D-prstenom

A synthetic sequence has been developed for the preparation of 9,10-di-O-diacetyl-4-desmethylene-4 beta-(3-butenyl)-4 alpha-hydroxy-5-O-mesyltaxicin I-1,2-carbonate 3, an intermediate in an attempted synthesis of a cyclobutane paclitaxel analogue. A series of reactions of 3 were investigated, including the protection of the sterically hindered C-4 alpha-hydroxy group and the oxidative cleavage of the terminal double bond. Cyclization of 13 to the cyclobutane-containing intermediate failed due to the unexpected instability of the dimethylsilane protecting group under basic conditions.Razvijena je sintetička sekvenca za dobijanje 9,10-di-O-acetil-4-desmetilen-4β-(3-butenil)-4α-hidroksi-5-O-meziltaksicin I-1,2-karbonata (3), intermedijera u pokušanoj sintezi ciklobutanskog analoga paklitaksela. Ispitivana je mogućnost dalje hemijske transformacije jedinjenja 3, kao što je zaštita sterno izrazito zaštićene C-4α hidroksilne grupe i oksidativna fragmentacija terminalne dvostruke veze. Ciklizacija jedinjenja 13 nije dala željeni rezultat - intermedijer sa ciklobutanovim prstenom, što je posledica neočekivane nestabilnosti DMS-zaštitne grupe u baznim reakcionim uslovima

Semisynthesis of Taxol (R): an improved procedure far the isolation of 10-deacetylbaccatin III

From the needles of domestic yew, (Taxus baccata), 10-deacetylbaccatin III (10-DAB) call be isolated in quantities of up to 297 mg per kg of fresh needles. Additional quantities of 10-DAB call be obtained from the extract by NaBH4 mediated reductive hydrolysis of baccatin esters. A four-step procedure converts 10-DAB into taxol in 58% overall yield

Cyclopentane ring formation in the cycloaddition reaction of 3-alkenyl radicals to radicophilic olefins

Regioselective additions of 3-alkenyl radicals (10 and 20) to electron deficient olefinic bonds (7 and 17), followed by intramolecular 5- exo-cyclization and repeated addition to radicophilic double bonds were investigated and combined into a sequence of reactions for the preparation of cyclopentane derivatives (9 and 19). High regioselectivity of 3-alkenyl radical (10) addition to the electron deficient olefinic bond (7) as well as of 5-exo -cyclization of intermediary 5-hexenyl type radical (11), was achieved. The fate of intermediary cyclopentylmethyl radicals (22 and 27) depends on the nature of substituents attached to radical carbon. In case of alkyl groups (22), the nucleophilic reactivity of radical intermediates was increased and an intermolecular addition reaction occurred with the formation of a new C-C bond. However, in case of aryl groups, mesomeric stabilization of the radical (27) suppress the addition reaction to the radicophilic olefinic bond, even when the latter was used in excess, in these cases only hydrogen abstraction takes place. © 1990

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

Model studija u sintezi epotilona - alternativni pristup sintezi C1-C7 fragmenta

In this model study an alternative synthetic approach to the C1-C7 fragment of epothilones was investigated. Starting froth 4,4-dimethylcyclopentenone, a 7 step reaction sequence afforded the key intermediate 7 in 27%, overall yield. Surprisingly, the attempted deprotection of latent functionalities in 7 failed, indicating the incompatibility of the ethoxyethyl protective group with the reaction conditions employed.U okviru model studije ispitivan je alternativni sintetički pristup C1–C7 fragmentu molekula epotilona. Polazeći od 4,4-dimetilciklopentenona, ključni intermedijer 7 dobijen je u sedam faza, u ukupnom prinosu od 27 %. Deprotekciju latentnih funkcionalnih grupa u molekulu 7 nije bilo moguće izvršiti, zbog iznenađujuće labilnosti etoksietil zaštitne grupe u baznim reakcionim uslovima

Supplementary data for the article: Vulović, B.; Marić, I.; Matović, R.; Saicíć, R. N. Synthesis of Vinyldihydropyran by Cooperative Catalysis. Journal of the Serbian Chemical Society 2016, 81 (12), 1335–1343. https://doi.org/10.2298/JSC161102103V

Supplementary material for: [https://doi.org/10.2298/JSC161102103V]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2388

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

Synthesis of Natural Products and the Development of Synthetic Methodology: The Case Study of (-)-Atrop-abyssomicin C

During our attempt to follow the planned synthetic route to the naturally occurring antibiotic (-)-atrop-abyssomicin C, we encountered two shortcomings, which forced us to reconsider our tactics and find new methods to overcome the problems. These methods turned out to be of general applicability, as demonstrated later in total syntheses of two other natural products: (+)-allokainic acid and (-)-gabosine H. The paper provides a brief account of these endeavors

Supplementary data for article: Bihelović, F.; Karadžić, I.; Matović, R.; Saičić, R. Total Synthesis and Biological Evaluation of (-)-Atrop-Abyssomicin C. Organic and Biomolecular Chemistry 2013, 11 (33), 5413–5424. https://doi.org/10.1039/c3ob40692j

Supplementary material for: [https://doi.org/10.1039/c3ob40692j]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1388

Supplementary data for article: Trajković, M.; Ferjančić, Z.; Saičić, R. An Aldol Approach to the Enantioselective Synthesis of (-)-Oseltamivir Phosphate. Organic and Biomolecular Chemistry 2011, 9 (20), 6927–6929. https://doi.org/10.1039/c1ob06248d

Supplementary material for: [https://doi.org/10.1039/c1ob06248d]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1210