A new route toward 4-substituted pyrazino[2,1-b] qiuinazoline-3,6-dione systems. Total synthesis of glyantrypine

Treatment of sodium N-(o-azidobenzoyl)aminoacylglycinates 8 with acetic anh ydride afforded 1-acetyl-4-(o-azidobenzoyl)-2,5-piperazinediones 7, with co mplete retention of the stereochemistry. The intramolecular aza Wittig reac tions of compounds 7 in the presence of tributylphosphine followed by deace tylation gave 1,2-unsubstituted pyrazino[2,1-b]quinazoline-3,6-diones 1. Th is route was adapted to the synthesis of both enantiomers of the alkaloid g lyantrypine.