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A Convergent Total Synthesis of the Telomerase Inhibitor (±)‐γ‐Rubromycin
Author(s) -
Wilsdorf Michael,
Reissig HansUlrich
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201400315
Subject(s) - moiety , isocoumarin , phosphonate , total synthesis , aryl , chemistry , stereochemistry , reagent , silyl ether , convergent synthesis , aldehyde , combinatorial chemistry , silylation , organic chemistry , catalysis , alkyl
Abstract The total synthesis of the human telomerase inhibitor γ‐rubromycin in its racemic form was accomplished in 3.8 % overall yield. The key feature of this synthesis is an efficient acid‐catalyzed spiroketalization for the construction of the spiroketal core. The required electronically well‐balanced spiroketal precursor was obtained by the convergent assembly of a naphthyl‐substituted aldehyde, an α‐methoxyallyl‐γ‐silyl‐substituted phosphonate as the central C 3 building block, and a highly functionalized aryl Grignard reagent. Another key feature is the late‐stage construction of the isocoumarin moiety and a simultaneous protodesilylation furnishing the known methyl aryl ether protected precursor of γ‐rubromycin.