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Asymmetric α‐Hydroxylation of a Lactone with Vinylogous Pyridone by Using a Guanidine–Urea Bifunctional Organocatalyst: Catalytic Enantioselective Synthesis of a Key Intermediate for (20 S )‐Camptothecin Analogues
Author(s) -
Watanabe Tatsuya,
Odagi Minami,
Furukori Kota,
Nagasawa Kazuo
Publication year - 2014
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.201303633
Subject(s) - enantioselective synthesis , chemistry , bifunctional , guanidine , lactone , catalysis , hydroxylation , indolizine , organocatalysis , stereochemistry , camptothecin , combinatorial chemistry , organic chemistry , enzyme
We have developed a catalytic asymmetric synthesis of ( S )‐4‐ethyl‐6,6‐(ethylenedioxy)‐7,8‐dihydro‐4‐hydroxy‐1 H ‐pyrano[3,4‐ f ]indolizine‐3,10(4 H )dione ( 5 a ), a synthetic intermediate for (20 S )‐camptothecin analogues. A key step in this synthesis is an asymmetric α‐hydroxylation of a lactone with a vinylogous pyridone structure ( 8 a ) by using a guanidine–urea bifunctional organocatalyst. The present oxidation was successfully applied to the synthesis of C20‐modified derivatives of (+)‐C20‐desethylbenzylcamptothecin ( 13 ).