Synthetic studies towards D-modified paclitaxel analogues
Sintetičke studije analoga paklitaksela sa modifikovanim D-prstenom
Abstract
A synthetic sequence has been developed for the preparation of 9,10- di-O-diacetyl-4-desmethylene-4β-(3-butenyl)-4α-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-4α-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.
Keywords:
taxoids / taxanes antitumor agents / radical allylation / silyl protecting groupsSource:
Journal of the Serbian Chemical Society, 2012, 77, 11, 1529-1539Publisher:
- Serbian Chemical Soc, Belgrade
Funding / projects:
DOI: 10.2298/JSC120626094F
ISSN: 0352-5139
WoS: 000312746700002
Scopus: 2-s2.0-84871825026
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Institution/Community
IHTMTY - JOUR AU - Ferjančić, Zorana AU - Matović, Radomir AU - Saičić, Radomir N. PY - 2012 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/1056 AB - A synthetic sequence has been developed for the preparation of 9,10- di-O-diacetyl-4-desmethylene-4β-(3-butenyl)-4α-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-4α-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. AB - 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. PB - Serbian Chemical Soc, Belgrade T2 - Journal of the Serbian Chemical Society T1 - Synthetic studies towards D-modified paclitaxel analogues T1 - Sintetičke studije analoga paklitaksela sa modifikovanim D-prstenom VL - 77 IS - 11 SP - 1529 EP - 1539 DO - 10.2298/JSC120626094F ER -
@article{ author = "Ferjančić, Zorana and Matović, Radomir and Saičić, Radomir N.", year = "2012", abstract = "A synthetic sequence has been developed for the preparation of 9,10- di-O-diacetyl-4-desmethylene-4β-(3-butenyl)-4α-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-4α-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.", publisher = "Serbian Chemical Soc, Belgrade", journal = "Journal of the Serbian Chemical Society", title = "Synthetic studies towards D-modified paclitaxel analogues, Sintetičke studije analoga paklitaksela sa modifikovanim D-prstenom", volume = "77", number = "11", pages = "1529-1539", doi = "10.2298/JSC120626094F" }
Ferjančić, Z., Matović, R.,& Saičić, R. N.. (2012). Synthetic studies towards D-modified paclitaxel analogues. in Journal of the Serbian Chemical Society Serbian Chemical Soc, Belgrade., 77(11), 1529-1539. https://doi.org/10.2298/JSC120626094F
Ferjančić Z, Matović R, Saičić RN. Synthetic studies towards D-modified paclitaxel analogues. in Journal of the Serbian Chemical Society. 2012;77(11):1529-1539. doi:10.2298/JSC120626094F .
Ferjančić, Zorana, Matović, Radomir, Saičić, Radomir N., "Synthetic studies towards D-modified paclitaxel analogues" in Journal of the Serbian Chemical Society, 77, no. 11 (2012):1529-1539, https://doi.org/10.2298/JSC120626094F . .