Biosynthetic pathways to dichloroimines; precursor incorporation studies on terpene metabolites in the tropical marine sponge Stylotella aurantium.
The biosynthetic origin of the dichloroimine functional group in the marine sponge terpene metabolites stylotellanes A (3) and B (4) was probed by the use of [(14)C]-labelled precursor experiments. Incubation of the sponge Stylotella aurantium with [(14)C]-labelled cyanide or thiocyanate resulted in radioactive terpenes in which the radiolabel was shown by hydrolytic chemical degradation to be associated specifically with the dichloroimine carbons. Additionally, label from both precursors was incorporated into farnesyl isothiocyanate (2). A time course experiment with [(14)C]-cyanide revealed that the specific activity for farnesyl isothiocyanate decreases over time, but increases for stylotellane B (4), consistent with the rapid formation of farnesyl isothiocyanate (2) from inorganic precursors followed by a slower conversion to stylotellane B (4). The advanced precursors farnesyl isothiocyanate (2) and farnesyl isocyanide (5) were supplied to S. aurantium, and shown to be incorporated efficiently into stylotellane A (3) and B (4). Feeding of [(14)C]-farnesyl isothiocyanate (2) resulted in a higher incorporation of label than with [(14)C]-farnesyl isocyanide (5). Farnesyl isocyanide was incorporated into farnesyl isothiocyanate in agreement with labelling studies in other marine sponges. Both farnesyl isocyanide and isothiocyanate were further incorporated into axinyssamide A (11) as well as the cyclized dichloroimines (12)-(14), (16) that represent more advanced biosynthetic products of this pathway. These results identify the likely biosynthetic pathway leading to the major metabolites of S. aurantium.
Simpson
Jamie S
JS
Department of Chemistry, School of Molecular and Microbial Sciences, The University of Queensland, Brisbane QLD 4072, Australia.
Brust
Andreas
A
Garson
Mary J
MJ
D000818:Animals; D002247:Carbon Isotopes; D003486:Cyanides / Q000737:chemistry / Q000378:metabolism; D007097:Imines / Q000737:chemistry / Q000378:metabolism*; D017879:Isothiocyanates / Q000737:chemistry / Q000378:metabolism; D008956:Models, Chemical; D011161:Porifera / Q000378:metabolism*; D017368:Protein Prenylation; D013729:Terpenes / Q000737:chemistry / Q000378:metabolism*
D002247:Carbon Isotopes; D003486:Cyanides; D007097:Imines; D017879:Isothiocyanates; D013729:Terpenes