457100-61-7Relevant academic research and scientific papers
Total synthesis of the antitumor macrolides, (+)-brefeldin A and 4-epi-brefeldin A from d-glucose: Use of the Padwa anionic allenylsulfone [3 + 2]-cycloadditive elimination to construct trans-configured chiral cyclopentane systems
Xiong, Ziyue,Hale, Karl J.
supporting information, p. 4254 - 4257 (2016/09/09)
A new synthesis of (+)-brefeldin A is reported via Padwa allenylsulfone [3 + 2]-cycloadditive elimination. Cycloadduct 13 was initially elaborated into iodide 27, which, following treatment with Zn, gave aldehyde 28 whose C(9) stereocenter was epimerized. Further elaboration into enoate 38 and Julia-Kocienski olefination with 5 subsequently afforded 39, which was deprotected at C(1) and O(15). Yamaguchi macrolactonization of the seco-acid thereafter afforded a macrocycle that underwent O-desilylation and inversion at C(4) to give (+)-brefeldin A following deprotection.
A "Chiral Aldehyde" Equivalent as a Building Block Towards Biologically Active Targets
Trost, Barry M.,Crawley, Matthew L.
, p. 2237 - 2252 (2007/10/03)
Chiral γ-aryloxybutenolides, readily accessible through dynamic kinetic asymmetric transformation (DYKAT) of racemic acyloxybutenolides, were utilized as "chiral aldehyde" building blocks for intermolecular cycloadditions and Michael reactions. Unprecedented selectivity in trimethylenemethane cycloadditions with this building block allowed an efficient synthesis of a novel metabotropic glutamate receptor 1 antagonist in development by the Bayer corporation. These studies further inspired work that culminated in the total synthesis of (+)-brefeldin A, a natural product with a range of significant biological properties. All of the stereochemistry in this target molecule was derived from two palladium-catalyzed asymmetric allylic alkylation reactions. The trans-alkenes were synthesized by a Julia olefination and a ruthenium-catalyzed trans-hydrosilylation-protodesilylation protocol. The route to (+)-brefeldin A lends itself to analogue syntheses and was completed in 18 steps in 6% overall yield.
4-Aryloxybutenolides as "chiral aldehyde" equivalents: An efficient enantioselective synthesis of (+)-brefeldin A
Trost, Barry M.,Crawley, Matthew L.
, p. 9328 - 9329 (2007/10/03)
4-(2′-Naphthoxy)-2-butenolide, readily available with high enantiopurity by a dynamic kinetic asymmetric transformation (DYKAT) of racemic 4-acyloxybutenolides (available in two steps from furfural), serves as an excellent chiral building block where the naphthoxy group strongly directs the stereochemistry of cycloadditions to the double bond. Notably, the cycloadditions of trimethylenemethanepalladium intermediates which do not exhibit good diastereoselectivity in additions to acceptors that possess many common and important chiral auxiliaries undergo cycloadditions with excellent regio- and stereocontrol. The utility of this process set the stage for an efficient new synthesis of (+)-brefeldin A, a compound of growing pharmacological significance. This synthesis also highlights the Pd-catalyzed DYKAT of crotyl carbonate to create the remote stereocenter. A new two-step method to convert aldehydes to δ-hydroxy-E-α,β-enoates is also outlined. Copyright
