1609272-73-2Relevant academic research and scientific papers
Total Synthesis, Stereochemical Revision, and Biological Reassessment of MandelalideA: Chemical Mimicry of Intrafamily Relationships
Willwacher, Jens,Heggen, Berit,Wirtz, Conny,Thiel, Walter,Fürstner, Alois
, p. 10416 - 10430 (2015/07/07)
MandelalideA and three congeners had recently been isolated as the supposedly highly cytotoxic principles of an ascidian collected off the South African coastline. Since these compounds are hardly available from the natural source, a concise synthesis rou
Catalysis-based total synthesis of putative mandelalide A
Willwacher, Jens,Fuerstner, Alois
supporting information, p. 4217 - 4221 (2014/05/06)
A concise synthesis of the putative structure assigned to the highly cytotoxic marine macrolide mandelalide A (1) is disclosed. Specifically, an iridium-catalyzed two-directional Krische allylation and a cobalt-catalyzed carbonylative epoxide opening served as convenient entry points for the preparation of the major building blocks. The final stages feature the first implementation of terminal-acetylene metathesis into natural product synthesis, which is remarkable as this class of substrates was beyond reach until very recently; key to success was the use of the highly selective molybdenum alkylidyne complex 42 as the catalyst. Although the constitution and stereochemistry of the synthetic samples are unambiguous, the spectra of 1 as well as of 11-epi-1 deviate from those of the natural product, which implies a subtle but deep-seated error in the original structure assignment. Bitter and sweet: The synthesis of the proposed structure of the cytotoxic macrolide mandelalide A reiterates the notion that structure elucidation of architecturally complex natural products is not always reliable. From the chemical viewpoint, the chosen route attests to the power of (transition) metals as catalysts for stereoselective synthesis. Most notable is the first application of terminal-acetylene metathesis to natural product chemistry.
