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Synthesis of 10,11‐Didehydro Cinchona Alkaloids and Key Derivatives
Author(s) -
Braje Wilfried M.,
Frackenpohl Jens,
Schrake Olaf,
Wartchow Rudolf,
Beil W.,
Hoffmann H. Martin R.
Publication year - 2000
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/(sici)1522-2675(20000412)83:4<777::aid-hlca777>3.0.co;2-w
Subject(s) - chemistry , cinchona alkaloids , stereochemistry , regioselectivity , cinchona , organic chemistry , enantioselective synthesis , catalysis
A series of 10,11‐didehydro Cinchona alkaloids containing an ethynyl group at C(3) were prepared efficiently in two steps from the naturally occurring Cinchona alkaloids ( Scheme 1 ). 10,11‐Didehydroquinine ( 4c ) and 10,11‐didehydroquinidine ( 4a ) belong to a significantly new class of semi‐natural Cinchona alkaloids. They are more polar and basic than the natural compounds and serve as versatile building blocks for further functionalization; they were transformed into the corresponding 11‐halo and 11‐pseudohalo derivatives and ( Z )‐vinyl halides ( Schemes 2 and 3 ). The conformation of the alkaloids was elucidated by NOE and X‐ray crystal diffraction analysis of 4a ( Fig .), and the cytostatic activity of selected didehydroquinidine derivatives was evaluated ( Table 5 ).