ISSN:
1434-193X
Keywords:
Natural products
;
Diterpenes
;
Ingenol
;
Antitumor agents
;
Isosters
;
Chemistry
;
General Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
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.
Additional Material:
1 Tab.
Type of Medium:
Electronic Resource
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