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Synthesis of Modified Ingenol Esters
Author(s) -
Appendino Giovanni,
Tron Gian Cesare,
Cravotto Giancarlo,
Palmisano Giovanni,
Annunziata Rita,
Baj Germano,
Surico Nicola
Publication year - 1999
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/(sici)1099-0690(199912)1999:12<3413::aid-ejoc3413>3.0.co;2-s
Subject(s) - chemistry , cytotoxicity , pinacol , diterpene , stereochemistry , chemical synthesis , derivative (finance) , combinatorial chemistry , organic chemistry , biochemistry , in vitro , catalysis , economics , financial economics
Synthetic protocols for the manipulation of the polyhydroxylated southern region of ingenol ( 1a ) were developed, and a series of isosteres of the anticancer compound ingenol 3,20‐dibenzoate ( 1b ) was prepared. The biological evaluation of these compounds showed that cytotoxicity was relatively tolerant to changes at C‐20, while PKC activation was markedly affected by these modifications. These data suggest that chemical manipulation can effectively dissect cytotoxicity and tumour‐promoting activity (or potential) of ingenoids, affording more optimal candidates for development, like 20‐deoxy‐20‐fluoroingenol 3,20‐dibenzoate ( 5b ). In mild acidic medium, an unexpected vinylogous retro‐pinacol rearrangement of ingenol to a tigliane derivative was observed.