Radioiodinated melatonin (N-acetyl-5-methoxytryptamine) has been in use for some years as a tool in radioimmune assay. The iodination by IC1 occurs at C-2 in very poor yield and produces a variety of other products, necessitating elaborate purification by HPLC. Since we had previously achieved the syntheses of 2-chloro- and 2-bromotryptophan in very good yield, we undertook a reexamination of the iodination problem. Initial efforts to achieve iodination of N-acetyltryptophan methyl ester were very disappointing. Far better results were obtained with the N- trifluoroacetyl derivative (65%) and further study showed that the introduction of all three halogens could be readily achieved without the need for the radical generators used in our earlier work. Further work demonstrated that effective halogenation depends on the degree of acidity of the acylamino NH group, with trifluoroacetylamino being the most acidic of the series. It now became obvious that replacement of the N-acetyl group of melatonin by N-trifluoroacetyl should improve the iodination yield considerably, and this alternative is now being explored. To our surprise, the N- trifluoroacetyl analogue had never been prepared and its biological activity, therefore, is not known. The compound will soon be evaluated for comparison in activity to the natural N-acetyl derivative. N- trifluoroacetylserotonin is also being prepared for parallel studies. Several years ago, we made a concerted effort to obtain 2-fluoroindoles by halogen exchange with 2-bromoindoles, but were unsuccessful. Direct fluorination by use of new fluorinating agents have now been surprisingly successful and such compounds are anticipated to find application as affinity labels, analogues of peptide hormones and PET scanning reagents (since the introduction of radiolabel requires only one step).
| Smith, B P; Tyler, M J; Kaneko, T et al. (2002) Evidence for biosynthesis of pseudophrynamine alkaloids by an Australian myobatrachid frog (pseudophryne) and for sequestration of dietary pumiliotoxins. J Nat Prod 65:439-47 |
| Dumbacher, J P; Spande, T F; Daly, J W (2000) Batrachotoxin alkaloids from passerine birds: a second toxic bird genus (Ifrita kowaldi) from New Guinea. Proc Natl Acad Sci U S A 97:12970-5 |
