cyclization
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- MeSH
- cyklizace fyziologie MeSH
- farmakologické účinky MeSH
- finanční podpora výzkumu jako téma MeSH
- prekurzory léčiv chemie MeSH
- Publikační typ
- přehledy MeSH
A new and diastereoselective method for the synthesis of the estrone skeleton from a substituted styrene based on sequential 3-fold use of Cp 2ZrBu 2 (oxidative addition-alkylation and two cyclization-alkylation sequences) and a ruthenium complex catalyzed RC-metathesis of a sterically hindered diene was developed. The prepared estratetraene was obtained in 7 steps from a commercially available starting material and thus the overall synthesis of estrone could be accomplished in 9 steps. Moreover, we have also found that the course of the reaction of substrates bearing the 2-halo-1,7-diene moiety with Cp 2ZrBu 2, i.e., cyclization or oxidative addition to the C-X bond, could be controlled by the nature of the halogen leaving group.
A new methodology useful for preparation of indole derivatives bearing a 2-(dialkylamino)-ethyl substituent at the 3-position has been developed. Application of this methodology to the synthesis of N,N-dimethyl-2-{5-[(1H-1,2,4-triazol-1-yl)methyl]-1H-indol-3-yl}ethan-1-amine (rizatriptan; 3) is described. The key reaction step is based on the radical cyclization of N-[4-(dimethylamino)but-2-yn-1-yl]-N-{2-iodo-4-[(1H-1,2,4-triazol-1-yl)methyl]phenyl}-acetamide (21), easily available by the Mannich reaction, and subsequent isomerization of the primarily formed methylidene derivative 22.
A novel pentamethinium salt was synthesized with an unforeseen expanded conjugated quinoxaline unit directly incorporated into a pentamethinium chain. The compound exhibited high fluorescence intensity, selective mitochondrial localization, high cytotoxicity, and selectivity toward malignant cell lines, and resulted in remarkable in vivo suppression of tumor growth in mice.
- MeSH
- chinoxaliny chemie terapeutické užití MeSH
- cyklizace MeSH
- hexamethonium chemie terapeutické užití MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory farmakoterapie patologie MeSH
- protinádorové látky chemie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
A unified strategy for the total synthesis of the methyl esters of all phytoprostane (PhytoP) classes bearing two ring-oxygen atoms based on an orthogonally protected common precursor is described. Racemic 16-F1t-, 16-E1-PhytoP and their C-16 epimers, which also occur as racemates in Nature, were successfully obtained. The first total synthesis of very sensitive 16-D1t-PhytoP succeeded, however, it quickly isomerized to more stable, but so far also unknown Δ13-16-D1t-PhytoP, which may serve as a more reliable biomarker for D-type PhytoP. The dioxygenated cyclopentane ring carrying the ω-chain with the oxygen functionality in the 16-position was approached by a radical oxidative cyclization mediated by ferrocenium hexafluorophosphate and TEMPO. The α-chain was introduced by a new copper-catalyzed alkyl-alkyl coupling of a 6-heptenyl Grignard reagent with a functionalized cyclopentylmethyl triflate.
The influence of side-chain structure on the mode of reaction of ortho-quinone amines has been investigated with a view, ultimately, to developing potential methods of therapeutic intervention by manipulating the early stages of melanogenesis. Four N-substituted dopamine derivatives have been prepared and quinone formation studied using pulse radiolysis and tyrosinase-oximetry. Ortho-quinones with an amide or urea side chain were relatively stable, although evidence for slow formation of isomeric para-quinomethanes was observed. A thiourea derivative cyclized fairly rapidly (k = 1.7/s) to a product containing a seven-membered ring, whereas a related amidine gave more rapidly (k approximately 2.5 x 10(2)/s) a stable spirocyclic product. The results suggest that cyclization of amides, ureas and carbamates (NHCO-X; X = R, NHR or OR) does not occur and is not, therefore, a viable approach to the formation of tyrosinase-activated antimelanoma prodrugs. It is also concluded that for N-acetyldopamine spontaneous ortho-quinone to para-quinomethane isomerization is slow.
- MeSH
- Agaricus enzymologie MeSH
- dopamin analogy a deriváty chemie MeSH
- financování organizované MeSH
- fungální proteiny chemie MeSH
- isomerie MeSH
- melaniny chemická syntéza chemie MeSH
- melanom enzymologie farmakoterapie MeSH
- molekulární struktura MeSH
- nádorové proteiny chemie MeSH
- oxidace-redukce MeSH
- prekurzory léčiv chemie MeSH
- protinádorové látky chemie terapeutické užití MeSH
- tyrosinasa chemie MeSH
