CHEMISTRY OF SECOLOGANIN - PART 5 - GRAPHICAL ANALYSIS OF THE ACIDIC DEGLYCOSYLATION OF VINCOSIDE DERIVATIVES

Acidic hydrolysis and cyclization were studied in vincoside glycosides ('natural' series) and their dihydro derivatives ('dihydro' series) i n which either one or both N atoms were free or blocked by an alkyl gr oup. For interpretation of the results, a graph was constructed in whi ch 25 points (actually circles) represent a maximum of 81 aglycone typ es and 40 arrows indicate 131 possible cyclizations. The reaction matr ix of the graph was under thermodynamic control and in most cases affo rded the thermodynamically most stable product aglycones. In addition to the deglycosylation, two types of cyclization were observed. In aza cyclizations, the preferred nucleophilic site is N-4 over N-1, and the preferred electrophilic site is C-22 in the glycosides, C-21 over C-1 9 and C-17 in aglycones. In oxacyclizations, the preferred nucleophili c site is O-17 over C-18 and C-21, and the preferred electrophilic sit e is C-19 over C-21 and C-17 in the 'natural' series, C-21 over C-17 i n the 'dihydro' series. In one case, the kinetically favoured aglycone types which had been generated in the reaction mixture were trapped i n a subsequent reaction (outside the graph) before thermodynamic equil ibrium was attained. With the help of graphical analysis it was possib le to justify the formation of the most favourable and actually isolat ed products and pathways out of a large number of possibilities. (C) 1 998 John Wiley & Sons, Ltd.