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Highly Enantioselective Organocatalytic Addition of Aldehydes to N ‐(Phenylmethylene)benzamides: Asymmetric Synthesis of the Paclitaxel Side Chain and Its Analogues
Author(s) -
Dziedzic Pawel,
Schyman Patric,
Kullberg Martin,
Córdova Armando
Publication year - 2009
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200900078
Subject(s) - enantioselective synthesis , paclitaxel , side chain , chemistry , catalysis , proline , organocatalysis , stereochemistry , combinatorial chemistry , organic chemistry , amino acid , biochemistry , cancer , polymer , medicine
Easily side‐tracked : A simple route to the paclitaxel side chain and its analogues is based on the ( R )‐proline‐catalyzed addition of aldehydes to N ‐(phenylmethylene)benzamides, followed by oxidation of the resulting protected α‐hydroxy‐β‐benzoylaminoaldehydes (92–99 % ee ). Esterification of the subsequent phenylisoserine derivatives with baccatin III gives paclitaxel analogues (see scheme).A simple highly enantioselective organocatalytic addition of aldehydes to N ‐(phenylmethylene)benzamides is presented. The application of ( R )‐proline as the catalyst and subsequent oxidation of the protected α‐hydroxy‐β‐benzoylaminoaldehydes (92–99 % ee ) gives access to esterification‐ready phenylisoserine derivatives such as the protected paclitaxel (taxol) side chain. Esterification of these derivatives with baccatin III gives access to the cancer chemotherapeutic substance paclitaxel and its analogues that do not exist in nature.