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Total Synthesis of a Hypothetical Macroketone of Migrastatin
Author(s) -
Choudhury Rahul,
Reddy D. Srinivasa
Publication year - 2021
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202100484
Subject(s) - chemistry , total synthesis , fascin , aldol reaction , stereochemistry , natural product , olefin fiber , combinatorial chemistry , actin , biochemistry , catalysis
Danishefsky's macroketone, a simplified analogue of natural product Migrastatin, is one of the lead compounds with potent cancer cell migration inhibition potential. Different biological assays suggest fascin protein as the potential target. Although it was indicated through X‐ray co‐crystallography where the concerned macroketone analogue was found to bind in the actin‐binding sites of fascin, there was a structural discrepancy, as the X‐ray co‐crystal structure suggested an E ‐olefin along with inversion of methyl stereochemistry from that of Danishefsky's macroketone. Here, we have accomplished the total synthesis of the ‘hypothetical macroketone’ for the first time. The TiCl 4 mediated vinylogous Mukaiyama aldol reaction is the key step in present synthesis.