Synthesis of 7-(15)N-Oroidin and evaluation of utility for biosynthetic studies of pyrrole-imidazole alkaloids by microscale (1)H-(15)N HSQC and FTMS.
Numerous marine-derived pyrrole-imidazole alkaloids (PIAs), ostensibly derived from the simple precursor oroidin, 1a, have been reported and have garnered intense synthetic interest due to their complex structures and in some cases biological activity; however very little is known regarding their biosynthesis. We describe a concise synthesis of 7-(15)N-oroidin (1d) from urocanic acid and a direct method for measurement of (15)N incorporation by pulse labeling and analysis by 1D (1)H-(15)N HSQC NMR and FTMS. Using a mock pulse labeling experiment, we estimate the limit of detection (LOD) for incorporation of newly biosynthesized PIA by 1D (1)H-(15)N HSQC to be 0.96 microg equivalent of (15)N-oroidin (2.4 nmole) in a background of 1500 microg of unlabeled oroidin (about 1 part per 1600). 7-(15)N-Oroidin will find utility in biosynthetic feeding experiments with live sponges to provide direct information to clarify the pathways leading to more complex pyrrole-imidazole alkaloids.
Wang
Yong-Gang
YG
Department of Chemistry, Texas A&M University, Texas 77842-3012, USA.
Morinaka
Brandon I
BI
Reyes
Jeremy Chris P
JC
Wolff
Jeremy J
JJ
Romo
Daniel
D
Molinski
Tadeusz F
TF
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011161:Porifera / Q000737:chemistry; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism
D000470:Alkaloids; D011758:Pyrroles; C077209:oroidin