Probing Ergot Alkaloid Biosynthesis: Synthesis and Feeding of a Proposed Intermediate along the Biosynthetic Pathway. A New Amidomalonate for Tryptophan Elaboration
The total synthesis of the diastereoisomeric amino acids 2 and their N-trideuteriomethyl analogues has been carried out.These compounds represent possible intermediates along the biosynthetic pathway from 4-(γ,γ-dimethylallyl)tryptophan (1) to the ergot alkaloids (e.g., 3a).The synthetic scheme features the preparation of an (indolylvinyl)metalic reagent from 4-ethynylindole via a hydrostannylation/metal-metal exchange sequence, as well as the preparation of dimethyl amino>malonate, a new amidomalonate reagent for tryptophan elaboration.Incorporation experiments with Claviceps sp.SD58 followed by GC-MS analysis of the major alkaloid, elymoclavine, showed that neither diastereomer of 2-d3 is an ergot alkaloid precursor.
Kozikowski, Alan P.,Okita, Makoto,Kobayashi, Motomasa,Floss, Heinz G.