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A Suzuki Cross‐Coupling and Intramolecular Aza‐Michael Addition Reaction Sequence Towards the Synthesis of 1,10b‐ epi ‐7‐Deoxypancratistatins and Their Cytotoxicity Studies
Author(s) -
Pandey Ganesh,
Balakrishnan Madhesan,
Swaroop Pandrangi Siva
Publication year - 2008
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200800830
Subject(s) - chemistry , michael reaction , intramolecular force , suzuki reaction , stereochemistry , coupling reaction , cytotoxicity , enone , epimer , combinatorial chemistry , organic chemistry , palladium , biochemistry , in vitro , catalysis
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 & Co. KGaA, 69451 Weinheim, Germany, 2008)