A Suzuki Cross‐Coupling and Intramolecular Aza‐Michael Addition Reaction Sequence Towards the Synthesis of 1,10b‐<i>epi</i>‐7‐Deoxypancratistatins and Their Cytotoxicity Studies

Abstract

Abstract The development of an efficient approach to the construction of a phenanthridone is described. The convergent strategy commences with the preparation of Suzuki cross‐coupling reaction precursors, arylboronic acid 12 and α‐iodo enone 19 , from piperonylamine ( 9 ) and (–)‐ D ‐quinic acid ( 10 ), respectively. The coupling of 12 and 19 followed by a key intramolecular aza‐Michael addition produced phenanthridone 21 featuring a cis ‐fused B–C ring junction. The syntheses of compounds 25 and 26 , both of which are C‐1 and C‐10b epimers of the naturally occurring potent antitumor agent 7‐deoxypancratistatin ( 2 ), from 21 are elaborated in detail in this paper. The cytotoxicities of 25 and 26 were evaluated against three different cancer cell lines. Compound 26 served as a moderate growth inhibitor of THP‐1 monocytic cells ( GI 50 = 14.5 μg/mL).(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2008)