symposium: sweeteners and sweetness theory on Discovery of Highly Sweet Compounds from Natural Sources A. Douglas Kinghorn’ and Edward J. Kennelly University of linois at Chicago, Chicago, IL 60612 ‘The organic constituents of plants may be divided into primary and secondary metabolites, with the former group, jal roles in cellular metabolism and the laté ter possessing more of an ecological role, and being of value { plant ssccidary metabolites have important and varied lises as pharmaceuticals, agrochemicals, and industrial materials ({-3)" It is from the plant secondary metabolite Class that a number of highly eweet natural products have} been found. Such compounds, in being so-called “high-po- tency sweeteners”, are, from abotlt’50 to over’ 1,000 times| the sweetness potency of sucrose and are represented by 2, variety of chemotypes. While there is every possibility tha’ highly eweet compoutid’ are prodticed by microorganistis, marine organisms,"and the more primitive plant forms, thus for all of the highly sweet natural products discovered, to date have been obtained from vascular plant sources (4)- Efforts to find additional examples of highly sweet plant constituents have been stimulated both by a public d mand for natural flavors, as well as perceived problérs ‘with the toxicity, taste quality, stability, or price of existing synthetic high-potency sweeteners. By following up eth- nobotanical leads to assist in the selection of candidate sweet-tasting plants, particularly those used medicinally by indigenous cultures, it is possible to discover new po- tently sweet natural product compounds, as will be ex- plained in greater detail in this review. In an earlier article In this Journal, the'term ethnobotany was defined and in. teresting plant secondary metabolites with a wide range of } __ biological activities were exemplified (6). in defense against insects and other pathogens (1): ses Importance of Plant-Derived Sweetening Agents ‘Throughout the world the most widely used sweetener is sucrose, obtained from either the sugar cane (Saccharum officinarum L.) or the sugar beet (Beta vulgaris L.) plant, (6), Sucrose is considered to be the quintessential sweet substance because the sweet taste it elicits in humans is; 4elean and is not associated with ariy aftertaste. In addition ' ‘fo taste considerations, sucrose has many other desirable ‘qualities as an ingredient in food: it is heat stable, watek soluble, cheap to produce, and a good bulking agent (7), In medieval Europe this compound was considered a great Tuxury (8), but today humans consume over 100 million metric tons per year of sucrose on a worldwide basis (9). Consider that in the United States, a typical 12-02. canof soda alone contains about 39 grams of sugar. Despite its current widespread use in the human diet, the USDA has recommended in its latest dietary guidelines that sugar Should be used sparingly (10). Of the reasons to lower hu- man sucrose consumption, the most compelling one is its propensity to cause dental caries (12), Since the 1960's @ Significant section of the market for sugar substitutes in the United States has been focused on high-potency sweet- ‘Presented before the Division of Chemical Education atthe 206th National Meeting ofthe American Chemical Society, August 22, 1983, Chicago, IL "uinor fo whom correspondence should be addressed. 676 Journal of Chemical Education [Although at one time saccharin was the only approved high-potency sweetener in the United States, this sub- stance has been joined on the market more recently by aspartame and acesulfame K. Other synthetic compounds of commercial promise as sucrose substitutes are alitame (12) and sucralose (12), and intensive efforts are being made to develop extremely sweet synthetic compounds, for example, of the guanidine and f-amino acid types (13). De- spite the fact that sweet-tasting compounds appear to be much less frequently encountered than bitter plant con- stituents, the plant kingdom already has afforded several natural high-potency sweeteners that are commercially ‘available in overseas countries. The number of different Structural types of natural sweeteners relative to the few compounds of this type so far known represents a quite remarkable track record of success. Currently, there are.about 75,plant-constituents known nich are Peprésentative of some 20 several-of:these:compounds have in sé mainly Japan For example, seaside (Fig\ira) is the major ent-kaurene glycoside of {ie Toaves of the South American herb, Stevia rebaudiana (Bertoni) Bertoni, and extracts of this plant containing stevioside and the related glycoside, rebaudioside A(Fig. 1, \2) have been usediiri Japan for sweetening foods and bev- ‘rages for about 20 yeas Tn 1988, S. rebaudiana sweeten- ters were estimated to posseas a larger share ofthe high-po- tency sweetener market in Japan than either saccharin or epartame (12), Stevioside also is an approved sweetener +, in Brazil and Korea (12).“Glucosyl stevioside”, which has a more pleasant taste than the parent compound and is also used as a sweetener in Japan;is a mixtire of products “obtained when the sugar, moieties of stoviosidé are trans.” ‘lycosyldted using a bacterial enzyme (14). Another sweet ener of considerable importance in Japa is the triterpene flycoside, glycyrthizin (Fig. 1, 9), which is extracted from the roots of Glyejrrhizarglabra L. and other species of this| genus; Ammoniated glyeyrehieih, has bees Weborded *Gen- erally Regarded as Safe" (GRAS) statad tithe United: States, and although sweet, is employed as a\favering cagent (2, 12). Thaumatins I and Ire small proteins ob- tained from the fruits of the West African plant, Thawma tococcus daniellii (Bennett) Benth., and a commercial preparation of a mixture of these proteins is used as a high-potency sweetener in Australia, Japan, and the United Kingdom (12). Extracts of other plants with more limited tse for sweetening in Japan are obtained from the dried fruits of Siratia grosvenorit (Swingle) C. Jeffrey {con- taining mogroside V (Fig. 1, 4) and other triterpene gly. Cosides} and from the fermented leaves of Hydrangea tracrophylla Seringe var. thunbergii (Siebold) Makino (containing phylloduleis Fig. 1,5), dihydroisocoumarin} te nidition to these natural sweeteners from plants, is, Mohesperidin dihydrochalcone (Fig. 1, 6), a semi-syn- Trolls derivative of a flavonoid glycoside of the peels of Seville oranges (Citrus auranticum L.), which is approved far limited use for sweetening purposes in Belgium (12).