The Synthesis of Eudistomins S and T: b-carbolines from the Tunicate Eudistoma olivaceum

libJtract -The syntheses of two k-arbnlines, eodistomins S and T, have been accomplished from tryptarnine precursors.Since the first reported activity against Her~es sim~lex virus, type I (HSV-l), by t,he tunicate (ancidian) organism Eudistoma, olivaceum,' m d the subsequent characterization artd structural elucidation of fifteen components of the organism by Rinehart &&'l3 in 1984, there has been 4 5 widespread interest in the structure and synthesis of these antiviral k a r b o l i n ~ derivativeu, collectively referred to as eudistomins, as well an closely related compounds such as eudistomidin-A.BRecently, the identification of three new members of the eudistomin series, endistonins R, S, and T, was reported by Kinzer and ~ardellina.~We now wish to report the total synthesis of eudistomin T(CfpH$rN20)4 and one of its closely related bramo-analogues, eudistomin S(C1gH13BrN20)5.The startingroaterials for the synthesis of eudistomina T and S, outlined above, were tryptmine and &brom~try~tamine,~ respectively.PictetSpengler condensation of the tryptmine with glyoxylic acid 9 produced, after esterification, the tetrahydro-karbolines (2a,b).Dehydrogenation to the harholine system could not be effected vith palladium in the presence of the broma+lubstituent and we have found elemental sulfur in refluxing xylenel0 to be the reagent of choice for this transformation.The final step was achieved in each case by a modified Grignard reaction1' on the esters %,h, providing 4 and 5 , in iaalated yields of 69% and 40% respectively.Only minor mounts of tertiary alcohol are formed under our