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Asymmetric Synthesis and Biological Evaluation of Glycosidic Prodrugs for a Selective Cancer Therapy
Author(s) -
Tietze Lutz F.,
von Hof J. Marian,
Krewer Birgit,
Müller Michael,
Major Felix,
Schuster Heiko J.,
Schuberth Ingrid,
Alves Frauke
Publication year - 2008
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200800250
Subject(s) - prodrug , adept , chemistry , glycosidic bond , enzyme , pharmacology , stereochemistry , combinatorial chemistry , biochemistry , medicine
A severe limitation in cancer therapy is the often insufficient differentiation between malign and benign tissue using known chemotherapeutics. One approach to decrease side effects is antibody‐directed enzyme prodrug therapy (ADEPT). We have developed new glycosidic prodrugs such as (−)‐(1 S )‐ 26 b based on the antibiotic (+)‐duocarmycin SA ((+)‐ 1 ) with a QIC 50 value of 3500 (QIC 50 =IC 50 of prodrug/IC 50 of prodrug+enzyme) and an IC 50 value for the corresponding drug (prodrug+enzyme) of 16 p M . The asymmetric synthesis of the precursor (−)‐(1 S )‐ 19 was performed by arylation of the enantiomerically pure epoxide (+)‐( S )‐ 29 (≥98 % ee ).