A Single-Step Synthesis of Xyridins A and B, Metabolites from Xyris indica

Abstract

A facile single-step synthesis of the title isocoumarins isolated from Xyris indica has been elaborated. Condensation of butanoyl chloride and 2-oxobutanoyl chloride with 3,4-methylenedioxyhomophthalic acid afforded xyridin A and xyridin B, respectively. Xyridin A was saponified to the corresponding keto acid, which on reduction gave the (±)-3,4-dihydro-6,7-methylenedioxy-3-propylisocoumarin in which diastereotopy of the methylenic protons around the stereogenic center was observed. A mass fragmentation mechanism for xyridins has also been suggested.In 1995, Ruangrungsi et al. isolated from the nonpolar fraction of the chloroform extract of the flowering heads of the weed Xyris indica two new isocoumarins, which they named xyridins A and B [1]. Xyris indica L. (tall yellow-eyed grass) is one of the five species of the genus Xyris found throughout Thailand and is known locally as "Kra thin thung". In Bengal the plant has been used in folk medicine as a cure for ring worm, itch, and leprosy. The structures of xyridin A and B were established by modern spectroscopic techniques as 6,7-methylenedioxy-3-propylisocoumarin (1a) and 6,7-methylenedioxy-3-(1-oxopropyl)isocoumarin (1b), respectively. O O O O X 1a,b 1 a X = H 2 , b X = OAlthough xyridins A and B, like the majority of other naturally occurring isocoumarins derived biogenetically from acetate via the acetate-polymalonate pathway, possess a C(8) or C(6) and C(8) oxygenation, xyridins A and B are unique in being 3-alkyl/acyl-substituted 6,7-methylenedioxyisocoumarins. In the literature unsubstituted 4,5-, 6,7-methylenedioxyisocoumarins and 4,5-, 5,6-, 6,7-methylenedioxy-3,4-dihydroisocoumarins are known along with 3-methyl-6,7-methylenedioxy-3,4-dihydroisocoumarin as the only example of a 3-alkyl-substituted 6,7-methylenedioxyisocoumarin [2][3][4]. Some important examples of other natural products bearing a 6,7-methylenedioxydihydroisocoumarin moiety are hippeastrine [5], tetrabenzylcorricidin [6], lycoricidin [7], pancratistatin [8,9], and tazettine [10]. Peshawarine contains an 3-aryl-7,8-methylenedioxy-3,4-dihydroisocoumarin skeleton [11]. __________________________________________________________________________________________