Synthesis of 10,11‐Didehydro Cinchona Alkaloids and Key Derivatives

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).