15601-13-5Relevant academic research and scientific papers
Total synthesis of berkelic acid
Snaddon, Thomas N.,Buchgraber, Philipp,Schulthoff, Saskia,Wirtz, Conny,Mynott, Richard,Fuerstner, Alois
supporting information; experimental part, p. 12133 - 12140 (2011/02/25)
A productive total synthesis of both enantiomers of berkelic acid (1) is outlined that takes the structure revision of this bioactive fungal metabolite previously proposed by our group into account. The successful route relies on a fully optimized triple-deprotection/1,4-addition/spiroacetalization cascade reaction sequence, which delivers the tetracyclic core 32 of the target as a single isomer in excellent yield. The required cyclization precursor 31 is assembled from the polysubstituted benzaldehyde derivative 20 and methyl ketone 25 by an aldol condensation, in which the acetyl residue in 20 transforms from a passive protecting group into an active participant. Access to fragment 25 takes advantage of the Collum-Godenschwager variant of the ester enolate Claisen rearrangement, which clearly surpasses the classical Ireland-Claisen procedure in terms of diastereoselectivity. Although it is possible to elaborate 32 into the target without any additional manipulations of protecting groups, a short detour consisting in the conversion of the phenolic -OH into the corresponding TBS-ether is beneficial. It tempers the sensitivity of the compound toward oxidation and hence improves the efficiency and reliability of the final stages. Orthogonal ester groups for the benzoate and the aliphatic carboxylate terminus of the side chain secure an efficient liberation of free berkelic acid in the final step of the route. Queue up: Three deprotection and three bond-forming reactions, all of which are effected just by a trace of HCl, zip an easily attained enone to the polycyclic core of berkelic acid in diastereomerically pure form and essentially quantitative yield. This cascade process paves the way to a concise and effective total synthesis of this alleged metalloproteinase-3 inhibitor and cytotoxic metabolite derived from an extremophilic fungus.
A synthesis-driven structure revision of berkelic acid methyl ester
Buchgraber, Philipp,Snaddon, Thomas N.,Wirtz, Conny,Mynott, Richard,Goddard, Richard,Fuerstner, Alois
scheme or table, p. 8450 - 8454 (2009/05/07)
A subtle difference: A single step suffices to transform a linear precursor into the chromane spiroketal core of the metalloproteinase-3 inhibitor berkelic acid by an acid-catalyzed deprotection/Michael addition/acetalization cascade. This efficient route
Enantioselective Synthesis of (R)-(+)-Pulvilloric Acid
Roedel, Thomas,Gerlach, Hans
, p. 213 - 216 (2007/10/03)
The fungal metabolite (R)-(+)-pulvilloric acid was synthesized for the first time.Reaction of the Grignard reagent of 5 with 2-pentyloxirane (S)-(-)-4 in the presence of 1,5-cyclooctadienecopper(I) chloride as the catalyst led to (S)-(+)-6.The ena
