112497-13-9Relevant articles and documents
Synthesis, Profiling, and Bioactive Conformation of trans-Cyclopropyl Epothilones
Kuzniewski, Christian N.,Glauser, Simon,Gaugaz, Fabienne Z.,Schiess, Raphael,Rodríguez-Salarichs, Javier,Vetterli, Stefan,Horlacher, Oliver P.,Gertsch, Jürg,Redondo-Horcajo, Mariano,Canales, Angeles,Jiménez-Barbero, Jesús,Díaz, José Fernando,Altmann, Karl-Heinz
, (2019/05/10)
A series of new 3-deoxy-C(12),C(13)-trans-cyclopropyl-epothilones have been prepared, bearing benzothiazole, quinoline, thiazol-5-ylvinyl, or isoxazol-3-ylvinyl side chains. For analogs with fused aromatic side chains, macrocyclic ring-closure was based on ring-closing olefin metathesis (RCM) of a precursor incorporating the fully elaborated heavy atom framework of the target structure (including the side chain moiety), while side chain attachment for the thiazole and isoxazole-containing 16-desmethyl analogs was performed only after establishment of the macrolactone core. Two approaches were elaborated for a macrocyclic aldehyde as the common precursor for the latter analogs that involved ring-closure either by RCM or by macrolactonization. Benzothiazole- and quinoline-based analogs were found to be highly potent antiproliferative agents; the two analogs with a thiazol-5-ylvinyl or an isoxazol-3-ylvinyl side chain likewise showed good antiproliferative activity but were significantly less potent than the parent epothilone A. Surprisingly, the desaturation of the C(10)?C(11) bond in these analogs was associated with a virtually complete loss in antiproliferative activity, which likely reflects a requirement for a ca. 60 ° C(10)?C(11) torsion angle in the tubulin-bound conformation of 12,13-trans-epothilones.
Lewis-acid catalyzed formation of dihydropyrans
Hanessian, Stephen,Focken, Thilo,Oza, Rupal
, p. 9870 - 9884 (2012/02/06)
A methodology is described for the synthesis of 2,6-disubstituted dihydro[2H]pyrans through a Lewis-acid catalyzed 6-endo-trig cyclization of β-hydroxy-γ,δ-unsaturated alcohols. Employing alkyl-substituted allylic diols and catalytic amounts of a Lewis ac
Diastereoselective dihydroxylation and regioselective deoxygenation of dihydropyranones: A novel protocol for the stereoselective synthesis of C 1-C8 and C15-C21 subunits of (+)-discodermolide
Ramachandran, P. Veeraraghavan,Prabhudas, Bodhuri,Chandra, J. Subash,Reddy, M. Venkat Ram
, p. 6294 - 6304 (2007/10/03)
Diastereoselective dihydroxylation of dihydropyranones and subsequent regioselective α-deoxygenation provides 1,3-trans-β-hydroxy-6- lactones stereoselectively. This protocol has been applied for the synthesis of C1-C8 and C15-C21 subunits of (+)-discodermolide.
