Abstracts of the 21st Annual Convention (1990)
There is a great deal of interest in the discovery of additional examples of highly sweet nonnutritive organic molecules that do not promote dental caries. To find widespread application, such compounds should be potently sweet and exhibit taste qualities as close as possible to those of sucrose. In addition, they should be determined as completely safe for human consumption and be noncariogenic, as well as being thermally and hydrolytically stable, soluble in water, and economic to produce by synthesis or cultivation.^1) Nearly 50 naturally occurring intensely sweet substances are now known, and all of these have so far been found as constituents of green plants, rather than of microorganisms, marine life forms, or insects. It appears that these sweet compounds occur in a random fashion in flowering plants. Thus far, the majority of highly sweet compounds derived from plants have proven to be either terpenoids, flavonoids, or proteins. Several naturally occurring intensely sweet molecules have commercial importance as sucrose substitutes in one or more countries, including glycyrrhizin, stevioside, and thaumatin.^2) While Tanaka and co-workers at Hiroshima University in Japan have found various Chinese medicinal plants to be excellent sources of novel highly sweet compounds such as baiyunoside, carnosiflosid V and rubusoside,^3) we have concentrated on North and South American medicinal plants in our efforts to discover new natural sweeteners. Among the novel highly sweet compounds that have been studied recently in our laboratory are the sweet sesquiterpene, hernandulcin, which was initially isolated from Lippia dulcis grown in Mexico;^4) the labdane diterpene arabinoside, gaudichaudioside A, from Baccharis gaudichaudiana collected in Paraguay;＾5) the cycloartane-type triterpene glycosides, abrusosides A-D, from Abrus precatorius leaves obtained in Florida;＾6) the steroidal saponins, polypodosides A and B from Polypodium glycyrrhiza gathered in Oregon;＾7) and the dihydroflavonol, dihydroquercetin-3-acetate from a further Paraguayan plant, Tessaria dodoneifolia.＾8) We have used the latter compound as a prototype molecule to synthesize its much sweeter 4´-methyl ether,＾8) and have identified further sweet dihydroflavonols from the Texan plant, Hymenoxys turneri.＾9) In our laboratory investigations on natural sweeteners, we have approached the problem of identifying candidate sweet plants for study by careful analysis of the literature and by observations made in the field. Preliminary extracts of plants are routinely assessed for sweetness only after the performance of mutagenicity and acute toxicity studies. Sweet compounds are then isolated by activity-guided fractionation, and modern spectroscopic methods are employed for compound structure elucidation. Recently, we have investigated the use of electrophysiological and behavioral (conditioned taste avoidance) experiments on the Mongolian gerbil, in order to predict the sweetness of plant extracts and pure compounds for humans and thus reduce the need for expensive preliminary safety assessments.＾10) We have also investigated sweet constituents such as stevioside and rebaudioside A of the “sweet herb of Paraguay”, Stevia rebaudiana. It has been shown that their common aglycone, st-eviol(13-hydroxy-ent-kaurenoic acid), is mutagenic in a forward mutation assay utilizing Salmonella typhimurium strain TM677.＾11) Work on the in vitro metabolism of steviol has led to the observation that 15-oxosteviol is a direct-acting mutagen in this same test system.＾12) These results have relevance for human populations in countries which presently permit the use of S. rebaudiana products as food additives, namely, Japan, Brazil and Korea. 1. G.E. DuBois, Ann. Rep. Med. Chem. 17, 323(1982). 2. A.D. Kinghorn and D.D. Soejarto, Med. Res. Rep. 9, 91 (1989). 3. O. Tanaka, Kagaku to Kogyo (Osaka) 61, 404 (1987). 4. C.M. Compadre, J.M. Pezzuto, A.D. Kinghorn and S.K. Kamath, Sc
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