Irritant principles of the mezereon family (Thymelaeaceae), V. New skin irritants and tumor promoters of the daphnane and 1 alpha-alkyldaphnane type from Synaptolepis kirkii and Synaptolepis retusa.

Abstract

Seventeen mostly new, skin irritant diterpene esters (DTE) of the daphnane and 1 alpha-alkyldaphnane types were isolated from roots of Synaptolepis kirkii and Synaptolepis retusa. The parent alcohols of the daphnane types are shown to be 5 beta-hydroxyresiniferonol-6 alpha,7 alpha-oxide [1] and 5 beta, 12 beta-dihydroxyresiniferonol-6 alpha,7 alpha-oxide [2]. Ten of the daphnane types are 9,13,14-orthoesters and three are conventional esters involving tertiary or secondary hydroxyl groups at C-13 or C-14, respectively. The latter may be considered immediate precursors of corresponding orthoesters. The four 1 alpha-alkyldaphnane types are intramolecular 9,13,14-ortho-(2-hexadecenoic acid)-esters in which, formally, the second to last C atom of the orthoester moiety is linked covalently to C-1 alpha of the diterpene parent alcohols 1 or 2. Thus, in the new structure, a macrocyclic ring bridges the alpha side of the diterpene moiety in an "ansa" type manner. The irritancies on the mouse ear of the DTE obtained cover a wide range (I24 = 0.05-670 nmole-1). Some of them are considerably more irritant than the daphnane type standard simplexin. Structure/activity investigations reveal that an ester group instead of a free hydroxyl group at C-20 ("cryptic types"), or presence of a hydroxy or an acetoxy group in position 12 diminishes the irritancies of the daphnane types isolated, similar to what is known in corresponding tigliane types. In the standardized initiation/promotion protocol on the back skin of mice, some of the irritant DTE exhibit tumor-promoting activities higher than that of simplexin.

• Authors: W Adolf, E H Seip, E Hecker, S F Dossaji
• Journal: Journal of natural products (J Nat Prod) 1988 Jul-Aug Vol. 51 Issue 4 Pg. 662-74 ISSN: 0163-3864 [Print] United States
• PMID: 3210015 (Publication Type: Journal Article)

Chemical References

• Carcinogens
• Diterpenes
• Irritants
• Terpenes
• mezerein

Topics

• Animals
• Carcinogens (isolation & purification)
• Chemical Phenomena
• Chemistry
• Diterpenes
• Irritants (isolation & purification)
• Lethal Dose 50
• Mice
• Plants, Toxic (analysis)
• Structure-Activity Relationship
• Terpenes (isolation & purification)