Open-Chain and Macrocyclic Polyethyleneglycol Esters of the Diterpenoid Isosteviol

Abstract

in which two isosteviol molecules were connected by polyethyleneglycol spacers were synthesized for the first time.The number of publications on chemical transformations of the ent-beyerane diterpenoid isosteviol (1, 16-oxo-entbeyeran-19-oic acid), which is obtained by acid hydrolysis of Stevia rebaudiana glycosides, has risen dramatically during the last five years [1]. Greater than 150 isosteviol derivatives have been reported [2]. We previously synthesized open-chain dinuclear isosteviol derivatives in which two ent-beyerane moieties were connected by polymethylene spacers with terminal esters via the reactions of isosteviol chloride with diols and of 16-dihydroisosteviol (8) with dibasic carboxylic acid chlorides [3,4]. Recently, two of these dinuclear derivatives, i.e., diacids 11 and 12, were transformed into dinuclear macrocycles in which two isosteviol ent-beyerane moieties were connected by diester spacers of different polymethylene chain lengths via reactions with diol ditosylates [5].

Diterpenoids of terrestrial origin

“…125,126 The sterebins O, P 1 and P 2 were isolated when the crude plant extract was fermented with Saccharomyces cerevisiae. 127 The ease of isolation of isosteviol by treatment of the crude extracts of S. rebaudiana with acid has led to a number of studies of its chemistry including the formation of glucuronic acid conjugates, 128 macrocyclic and polyethylene glycol esters, 129,130 triazole conjugates, 131 urea 132 and isoniazid derivatives. 133 A number of new tetracyclic diterpenoids have been isolated including 14b-hydroxy-3-oxo-ent-kaur-16-ene from Croton kongensis (Euphorbiaceae), 134 1a,3a,7b,18-tetrahydroxy-ent-kaur-16-ene (sideripullol A) from Sideritis pullulans, (Lamiaceae), 135 3-keto-6b,19-dihydroxy-ent-kaur-16-ene from a Saudi Arabian propolis, 136 7a,15b-dihydroxy-ent-kaur-16-ene from Hyalis argentea (Asteraceae) 137 and a glycoside related to atractyligenin from Vigna angularis (Leguminosae).…”