Download Dynemicin A, Uncialamycin and Analogues by Daniel Best, Mickael Jean, Pierre Van De Weghe PDF

By Daniel Best, Mickael Jean, Pierre Van De Weghe

Enediynes are common items with hugely lively cytotoxicity and antibacterial task, and hence have major capability within the improvement of anti-cancer treatments.  besides the fact that, they aren't on hand and will degrade quickly in the course of isolation; one resolution is to provide them utilizing overall synthesis. Dynemicin A and uncialamycin are such enediynes, with related constructions, for which overall synthesis has been achieved.  This publication offers the isolation and instruction of those compounds and their analogues via a variety of synthesis concepts. info of the structural components necessary to their anti-cancer task are provided, with the target of explaining and optimizing their organic actions and strength improvement as drugs.

  • Presents normal ènediynes with related buildings whose overall syntheses were accomplished
  • Explores structural analogs of training for reasons of optimizing the anti-cancer activity
  • Describes the complete syntheses of dynemicin A, the uncialamycine, in addition to analogs by way of emphasizing the synthesis options adopted
  • Features experiences of the organic actions and information to convey out the structural parts of those crucial compounds

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Additional resources for Dynemicin A, Uncialamycin and Analogues

Example text

HMPA or MoOPh) [VED 74]. Butyrolactone 2-241 was then reduced with lithium borohydride, and treatment with triphosgene led to selective carbonylation of the vicinal diol, giving 2-242. The remaining primary alcohol in 2-242 was oxidized to the corresponding carboxylic acid over two steps using Dess–Martin periodinane [DES 91] and Pinnick oxidation [LAS 05]. The carbonate was then hydrolyzed and the carboxylic acid methylated with diazomethane to give 2-243. Enol ether 2-244 was obtained by oxidative periodate cleavage of the diol, methylation of the resulting enol, and stereoselective epoxidation of the most electron-rich double bond.

Analogues featuring the tertiary ether linkage (2-197 to 2-199) are invariably far less active than the parent deoxy analogue 2-179. An enantiopure compound (+)-2-199, featuring a dynemicin-inspired core glycosylated with the calicheamicin oligosaccharide fragment, provides higher activity than the structurally simpler 2-197 and 2-198, but is still less potent than (+)-2-179. 8. As the epoxide bond weakens, a partial positive charge develops, which is stabilized by the resonance-donating N lone pair.

However, complexation of Co2(CO)8 to the propargyl alcohol’s triple bond, giving 2-277 or 2-278, allowed ring closure on treatment with trifluoromethanesulfonic anhydride in the presence of 2,6-di-tert-butylpyridine in nitropropane. Decomplexation of the triple bond with CAN then gave the carbamateprotected enediyne analogues 2-279 or 2-280, and finally cleavage of the carbamate with trifluoroacetic acid gave the analogue 2-281 or 2-282. The synthesis was performed in six steps from quinolines 2-270 and 2-271 in an overall yield of about 15%.

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