A structureactivity relationship study by Cook and Knox

For a gibberellin-like structure activity relationship study, acyloin-like cyclization involving the syntheses of steviol (1) and A-ring modified steviol analogues has been performed by Cook and Knox (1970 1976a 1976b) (Schemes 19 and 20). Synthesis of one of the steviol analogues commenced with OsO4-NaIO4 oxidation of a diol-ene (184) which gave the nor-keto-diol 185 (see Scheme 19). Baeyer-Villiger oxidation of 185 with perbenzoic acid and _p-TsOH afforded the -lactone 186, for which the 1,...

Absorption distribution and metabolism

In the rat, stevioside (125 mg kg p.o.) has a half-life of 24 hour, and is largely excreted in the feces in the form of steviol (Nakayama et al. 1986). Other metabolites include steviolbioside (see Figure 8.1). In this species, at least, metabolism appears to be mediated primarily by the gut microflora. Thus, 17-14C stevioside is converted to steviol by suspensions of rat intestinal microflora. Conversion is complete within two days (Wingard et al. 1980). The distribution of a derivative, 131I...

Acknowledgements

The Editor is grateful to all of the chapter authors, for lending their time and expertise to this project. In addition, he thanks the Book Series Editor, Dr Roland Hardman for his unwavering encouragement. Dr Aiko Ito is thanked for her helpful assistance in the editing of two of the chapters and the compilation of the index. Finally, the following are thanked for providing valuable information Professors Jan M.C.Guens, Pier-Giorgio Pietta, Finn Sand-berg and Vincente Oliverira Ferro, and Drs...

Aglycone moiety

Starting from rubusoside (7) (RS 114), the relative sweetnesses of the compounds with slightly modified skeletons were compared. The sugar units at C-13 and C-19 of the ent-kaurene skeleton seemed to be essential to express sweetness, since all ofthe monodesmosides, paniculosides I V (41 45) as well as suavioside E (22), K (23) and sugeroside (24) were tasteless.The only exceptions were the slightly sweet suavioside A (21) and I (27) which lack a sugar unit at C-19 and C-13, respectively. This...

Analytical Methods For The Sweet Stevia Rebaudiana Glycosides

A large number of analytical methods are available for the determination ofpurity and stability of stevioside and rebaudioside A, and such procedures have been applied to S. rebaudiana samples cultivated in different countries and climates, as well as foods and beverages containing these sweeteners (Kinghorn and Soejarto 1985 1991 Phillips 1987). Morever, sensitive analytical methodology is now available for the quantitation of stevioside and its metabolites such as isosteviol and steviol in...

Biosynthesis Of Stevioside And Steviol

The leaves of S. rebaudiana are very unusual in biosynthesizing such high concentration levels of stevioside, rebaudioside A, and the other sweet-tasting ent-kaurene glycoside constituents, which may accumulate to the extent of 10 w w or more (Kinghorn and Soejarto 1985 Phillips 1987). While the biosynthesis of stevioside takes place in the leaf chloroplasts of S. rebaudiana, there is still an incomplete picture of how this actually occurs. In an early study on S. rebaudiana leaves, it was...

Commercial Production Of Stevia Rebaudiana

The commercialization of S. rebaudiana leaves for sweetening and flavoring purposes has been quite rapid since first being introduced to Japan. In a recent year, about 200 metric tons of purified stevioside and other sweetener products were prepared from about 2,000 metric tons of dried plant leaves for the Japanese market (Kinghorn et al. 2001). As has been the case for some time, the vast majority of the S. rebaudiana leaves for the Japanese market is cultivated in the People's Republic of...

Conversion Of Steviol To Stevioside

Steviol (1) has been glycosylated to afford stevioside (2) (Ogawa ei al. 1978 1980) (Scheme 7). First, steviol was converted to steviolbioside from steviol methyl ester (73). Glycosidation (i) MgBra, 95 C, vacuum ( ) NaOMe, MeOH (iii) CF3S03Ag, 2,4,6-collidine (iv) NaOMe, MeOH (v) NaH, DMF, benzyl bromide (vi) NaOMe, MeOH (vii) Ac20, pyridine (viii) (Bu3Sn)20 (ix) Bn4NBr, CI(CH2)2CI (x) NaOMe, MeOH. Scheme 7 Conversion of steviol to stevioside. of 73 with 3, 4, 6-tri-O-benzyl-l, (74) in the...

Cooks approach toward the partial synthesis of steviol

The synthesis of steviol by Cook and Knox (1970 1976a 1976b) involves e i-kaur-16-en-19-oic acid (50) as the starting material (Scheme 4). Ozonolysis of methyl ester derivative 51 and subsequent oxidation gave keto-ester 52. Baeyer-Villiger oxidation of 52 gave 7-lactone 53 which was sequentially hydrolyzed, methylated, and oxidized to the corresponding keto-ester 54.The treatment of 54 with sodium liquid ammonia gave the acyloin-like cyclization product, diol-acid 55, which was oxidized to 56....

Flavonoids

Examination ofthe flavonoid content of S. rebaudiana leaves (Rajbhandari and Roberts 1983) resulted in the identification ofsix flavonoid glycosides in the ethyl acetate fraction, comprising apigenin 4'-O-glucoside (30), kaempferol 3-O-rhamnoside (31), luteolin 7-O-glucoside (32), quercetin 3-O-arabinoside (33), quercetin 3-O-glucoside (34), and quercetin 3-O-rhamnoside (quercitrin) (35) (Figure 4.5). These compounds were identified using standard Figure 4.5 Structures of flavonoids isolated...

Grandiflorenic acid synthesis

Starting from stevioside (2), the syntheses of grandiflorenic acid (123) and its analogues 124 and 125 have been carried out (Cheng and Zhou 1993a) (Scheme 11). Grandiflorenic acid (123), isolated from a Mexican medicinal plant,zoapatle (Montanoa tomentosa), has been reported to possess abortifacient activity (Lozoya et al. 1983).Methyl steviol (73), obtained by methylation ofsteviol (1), was acetylated and the double bond migrated on treatment with I2 to give 116. SeO2 oxidation of compound...

Hydroxylation of the bicyclo [321 octane system

It was found that the bicyclo 3.2.1 octane system of kaurene can be hydroxylated by treatment with molecular oxygen under light and subsequent LAH reduction (Bell et al. 1966b) (Scheme 16). The oxidation of olefin 159 was achieved by application of a photosensitized oxygenation procedure. The oxygenation of olefins invariably appeared to take place with allylic-type rearrangement of the double bond in highly stereoselective manner. In order to obtain the desired secondary alcohol 161, an...

I3d

Suavioside J (33) + H CH2OH 9-hydroxysuavioside J (34) - OH CH2OH suavioside H (35) + H CHO 9-hydroxysuavioside H (36) - OH CHO suavioside J (33) + H CH2OH 9-hydroxysuavioside J (34) - OH CH2OH suavioside H (35) + H CHO 9-hydroxysuavioside H (36) - OH CHO Figure 7.3 Diterpene glycosides from the leaves of Rubus suavissimus. Figure 7.3 Diterpene glycosides from the leaves of Rubus suavissimus.

Info

Source Korea Consumer Protection Board (1996b). Source Korea Consumer Protection Board (1996b). food from liquor. However, there are actually just two nations, Korea and Japan, where stevioside is now used in the manufacturing of liquor. The amounts of stevioside in soju used by various Korean companies is listed in Table 10.3. Two major companies producing soju (Jinro and Doosan Kyung Woul) use over 75 of the total amount of stevioside between them for this purpose, while the remaining...

Introduction

The genus Stevia belongs to the family Compositae1 within the tribe Eupatorieae. One member of this genus, S. rebaudiana (Bertoni) Bertoni, is of worldwide importance today. Its economic importance lies in the fact that the plant contains sweet-tasting ent-kaurene diterpenoid glycosides, in particular, stevioside and rebaudioside A, currently used as non-nutritive high potency sweeteners, primarily in Japan. The common name of this plant in the Guaran language of Paraguay is Ca he- or other...

Lethality and whole animal toxicity

In whole animal studies, stevioside has shown low toxicity (Akashi andYokoyama 1975 Fujita and Edahiro 1979 Lee et al. 1979 Yamada et al. 1985 Xili et al. 1992). From studies on crude Stevia extracts, it can be calculated that the acute LD50 of stevioside (i.p.) in rats is greater than 1700 mg kg body weight (Lee et al. 1979). For oral administration in mice, an LD50 of 8.2 g kg has been reported in one study (cited in Lee et al. 1979), and an LD50 of> 15 g kg has been calculated in another...

List of contributors

Institute Polit cnico Nacional Apartado Postal 14-740 M xico, D.F. 07000, Mexico College of Pharmacy Seoul National University San 56-1, Sinlim-dong Kwanak-ku College of Pharmacy Ewha Women's University 11-1 Daehyun-dong, Seodaemun-gu Seoul 120-750, Korea Department of Pharmacology College of Medicine University of Arizona P.O. Box 245050 Tucson, AZ 85724-5050 Formerly Emeritus Professor U.S. Food and Drug Administration Center for Food Safety and Applied Nutrition Office of Special...

Marketing In Japan

More than 20 years have passed since the use of stevia sweeteners started in Japan. At first, stevia sweeteners were expensive products priced at 100 thousand yen per kilogram. Since then, from progress made in refinement, cultivation, and plant breeding techniques, along with the increase in supplies of raw materials and crude extracts from other countries, prices went down and some of these products are currently sold at less than 10 thousand yen per kilogram. Although in earlier days S....

Miscellaneous Constituents

A number of common phytochemicals have been identified in S. rebaudiana, such as the pigments chlorophylls A and B and -carotene (see Table 4.1) (Cheng and Chang 1983).The same investigators also noted that various gums comprised about 7 15 of the total extracted solids from S. rebaudiana. Tartaric acid was the major organic acid in an extract of S. rebaudiana, with citric, formic, lactic, malic, and succinic acids also being identified (Cheng and Chang 1983). The phytohormone...

Miscellaneous sesquiterpenoids

The structures of sesquiterpenoids with a novel carbon framework isolated from Stevia species are illustrated in Figure 5.15. The jujuyane derivatives 148 and 149 are two rearranged germacranolides isolated from the aerial parts of S. jujuyensis from Argentina (Gil et al. 1992 De Guti rrez et al. 1992). This new skeleton could be formed by biological rearrangement of a 4-epi-tansanin (76) derivative (Gil et al. 1992). The aerial parts of S. isomeca yielded the xanthanolide 150 formed by ring...

Mst90

(Total steviol glycosides not less than 90 ) (Total steviol glycosides not less than 85.0 3.0 ) Stevia extract Glycyrrhizin 30-50 Sodium citrate Dextrin Stevia extract Glycyrrhizin 30-60 Sodium citrate Glycerol fatty acid ester Dextrin Sweetness property is similar to that of sucrose. All kinds of foods. Sweetness property is similar to that of sucrose. All kinds of foods. Applicability is facilitated by addition of dextrin. All kinds of foods. Product in which the taste is modified by addition...

Or2 O

187 R1 R2 R4 R5 R6 R7 H R3 OMe 188 R1 R2 R5 H R3 OMe R4 R7 Me R6 OH 189 R1 R3 OMe R2 R4 R5 R6 R7 H 190 R1 R3 OMe R2 R4 R5 R6 H R7 Me 191 R1 R3 OMe R2 R4 R5 H R6 OH R7 Me 193 R1 R2 R3 R5 R6 R7 H R4 Me 194 R1 OH R2 R3 R5 R6 R7 H R4 Me 195 Rl R2 R3 R4 R5 R6 H R7 Me 196 R1 OMe R2 R3 R4 R5 R6 H R7 Me 197 R1 R3 OMe R2 R5 H R6 OH R4 R7 Me

Or3

Sesquiterpene lactones constitute a large and diverse group of biologically active plant constituents of the Asteraceae, and as expected, some of the medicinal properties of Stevia could be a consequence of the presence in high yields of these compounds. Previous major reviews have discussed the chemistry, taxonomic significance and biological activities of this group of active principles (Marles et al. 1995 Robles et al. 1995). Costunolide (72), an active constituent ofseveral medicinal herbs,...

Pharmacological actions

Stevioside interferes with oxidative phosphorylation in isolated mitochondria (Vignais et al. 1966 Yamamoto et al. 1985 Kelmer Bracht, Alvarez et al. 1985 Kelmer Bracht, Kemmelmeier et al. 1985), with 50 inhibition seen at 1.2 mM (Vignais et al. 1966). This inhibition appears to be due to disruption of adenine dinucleotide translocation, a necessary process in shuttling high energy phosphate groups generated in mitochondria to their sites of consumption in the cell. In rat liver mitochondria,...

Properties Of Stevia Sweeteners

Although stevia sweeteners possess a slightly latent sweetness compared to sucrose, their use has been developing steadily.The wide use of stevia sweeteners is due to various characteristics as follows 1 Approximately 200 times sweeter than sucrose and costing comparatively less than sugar 2 Sweetness-quality superior to sucrose in mildness and refreshment 3 Sweetness is intensified by combining with salts and organic acids 4 The slightly latent sweetness is improved with the addition of sugars...

Pseudoguaianes

In contrast to the large number of structurally diverse guaianolides found in the genus Stevia, only four pseudoguaianolides have been isolated from two Mexican species. Figure 5.14 shows their structures. The aerial parts of S. rhombifolia afforded the first pseudoguaianolide isolated from Stevia, stevin (144) whose structure was deduced by NMR and chemical transformations (R os et al. 1967),while the aerial parts of S. isomecayielded pseudoguaianolides 145-147 (Bohlmann et al. 1985).

Pullulanase and pullulan

Through several screening procedures for selecting a better enzyme-donor system, one of the glucosidases, pullulanase from Klebsiella sp., proved to be effective. The products S1a, S2a, and S2c were also obtained from stevioside by pullulan and crude pullulanase. Although the yields were rather low, the selectivity in terms of the yield of the desirable S1a and S2a was Figure 1.1 HPLC chromatogram of transglucosylated products with CGTase (A) and pullulanase (B). HPLC conditions (A)...

R2

Figure 9.1 Structures of sweet ent-kaurene glycosides from the leaves of Stevia rebaudiana. leaves are called simply 'stevia sweeteners' and have been commercialized in three basic forms (i) 'stevia extract' (ii) 'sugar-transferred stevia extract' and (iii) 'rebaudioside A-enriched stevia extract', which have been used in a variety of foods and beverages. This chapter deals with the practical use of stevia sweeteners in Japan, referring to their developmental background and sweetening...

Rebaudioside A

Several attempts were made to increase the yield of rebaudioside A (2) by selective breeding of S. rebaudiana, and some individual plants exceeded the yield of Stevioside (1) as mentioned elsewhere in this volume.Also, a semisynthetic approach was successful in converting stevioside to rebaudioside A (2). Since rebaudioside A (2) has only one additional glucosyl moiety at the C-3 position of the inner glucose at C-13 of Stevioside, selective -glucosylation ofstevioside at this point would...

References

Abe, K. and Sonobe, M. (1977) Use of stevioside in the food industry. New Food Industry 19, 67 72. Akashi, H. (1977) Present status and prospect for stevioside for utilization. Shokuhin Kogyo 20(24), 20-26. Anonymous (1980) Concess o de registro e medicamento. Diario Official, Brazil, 19 September. Anonymous (1988a) High intensity sweeteners market size 7.2 billion yen. Stevia occupies 41 , but future gains will be made by aspartame. Food Chemicals, Tokyo, No. 6,19-26. Anonymous (1988b)...

Selective syntheses of improved sweeteners

Several attempts were carried out to produce more desirable sweeteners as selectively as possible starting from stevioside (1), rubusoside (7), and even from a mixture of several stevioside congeners for economic reasons. The tactical priority was the effective transfer of one or two glucosyl units to the 13-O-glucosyl (or sophorosyl) unit of the starting steviol glucoside. Trans-a-1,4-glucosylation of steviolmonoside and steviolbioside The first strategy for an effective transglucosylation was...

Shortening of the long a14 glucosyl chain

When undesirable products are obtained having 13-O-sugar units that are too long, it is necessary to shorten the sugar chain. -Amylase hydrolyzes a a-1,4-glucosyl chain from the non-reducing end to release maltose (4a-glucosyl glucose). By treatment with this enzyme, three or more additional a-1, 4-glucosyl chains of the 13-O-glucosyl moiety of transglucosylated steviol derivatives are converted into a mono- or di-a-1,4-glucosyl chain. In Japan, transglucosylated stevioside in which the...

Stability

Thermostability is an important factor when considering the applicability of sweeteners in heat-treatment such as cooking and disinfection. The sweetness property of an aqueous solution of stevioside does not change when heated to 95 C for 2 hours. When heated at 95 C for 8 hours, the sweetness falls slightly (Saizuka 1982). It is commonly known that stevia sweeteners do not decompose during their practical use. Stability in acidic and alkaline solution An acidic solution containing 0.02...

Steviol Glycosides

Stevioside (1) is a natural sweetener isolated from the herb, S. rebaudiana (Bertoni) Bertoni (Compositae) which is indigenous to Paraguay and has long been used to sweeten local beverages. It is a diterpene glucoside having the ent-kaurene diterpene aglycone, steviol, and is sweeter than sugar by about 150 times.The final structure elucidation of Stevioside (1) was performed by Mosettig et al. (1963). More than ten years later, several congeners of Stevioside were isolated from the same plant...

Structureactivity Relationships

Stevia rebaudiana and R. suavissimus supplied good lead compounds to study for structure sweetness relationships, since the former contains several glycosides (1 6) of the same aglycone, steviol, and the latter contains many glycosides (7 40 and 44), most of which have common sugar moieties (13- and 19-bis- -D-glucoside, 5) with slightly different aglycones. Several other structurally related glucosides,paniculosides I V (41 45), isolated from S.paniculata by Yamasaki et al. (1977) and from S....

Studies On Extracts

Many of the earlier toxicological studies of Stevia glycosides involved either water or ethanolic extracts of Stevia leaves containing stevioside and rebaudioside A at various concentrations Figure 8.1 Structures of some Stevia glycosides and related glycosides and aglycones. Figure 8.1 Structures of some Stevia glycosides and related glycosides and aglycones. (Planas and Kuc 1968 Oviedo et al. 1970 Akashi 1975 Akashi andYokoyama 1975 Lee et al. 1979 Takaki et al. 1984 Yamada et al. 1985 Medon...

Studies on the total synthesis of gibberellic acids

In a study on the total synthesis of gibberellic acids, the formation of the bicyclo 3.2.1 C D ring system present in stevioside (2) has been investigated (Corey et al. 1970) (Scheme 14). The crystalline tricarbocyclic ketal 141 was synthesized from the corresponding ketone 140 which in turn was obtained by a Robinson annelation sequence. Reaction of 2-(N-pyrrolidyl)indene with methyl vinyl ketone inTHF afforded a Michael (keto-enamine) adduct which was subjected to cyclization in dioxane...

Sugar moieties

Concerning the effect of the sugar moieties of steviol glycosides, several natural compounds from S. rebaudiana and R. suavissimus were examined.As was partly mentioned in the previous discussion,two saccharide moieties at C-13 and C-19 ester (bisdesmoside) seem to be important. These two sugar moieties, which are separated by the aglycone, are spatially very close to each other. From the results shown in Figure 7.1, when there are one or two C-19 ester sugars, the magnitude of sweetness and...

Sugartransferred stevia extract

A number of studies on the enzymatic transglycosylation of steviol glycosides have been carried out to increase their sweetness and to improve their quality of taste (Tanaka 1997 see Chapter 7). Of these, the trans-a-1,4-glucosylated product of the 'stevia extract' is produced by the following procedure and is commercially utilized in Japan. On treatment of 'stevia extract' with cyclomaltodextrin-glucanotransferase (CGTase) and a soluble starch, a-glucosyl units of the soluble starch are...

Summary And Conclusions

The sweet-tasting plant S. rebaudiana (Bertoni) Bertoni belongs to the genus Stevia (Compositae Eupatorieae), which comprises 220 230 species of herbs and shrubs found entirely in the Americas. The distribution range of Stevia extends from southern United States and Mexico, in the north, to Argentina, Chile and the Brazilian highlands, in the south, through the Central American States and the South American Andes. The North American species of the genus has recently been monographed (Grashoff...

Synthesis of 8acarboxymethyl podocarpan13one4carboxylate

A seco acid, (+)-8a-carboxymethyl podocarpan-13-one-4 -carboxylate (72), which retained all the asymmetric centers of steviol (1), except at C-13, has been obtained as one of the ozonolysis products of steviol methyl ester. A stereoselective total synthesis of this ( )-seco acid has been described (Mori and Matsui 1965) (Scheme 6). Methyl (7) was reduced with lithium tri-i-butoxyaluminum hydride to the corresponding hydroxy ester 68 which was converted to a crystalline vinyl ester 8 by a...

Synthesis of eikaur16en19oic acid

During the course ofsynthesizing grandiflorenic acid (123) (Lozoya et al. 1983), ent-kaur-16-en-19-oic acid (50) and its double bond isomer have been synthesized from stevioside (2) through two skeletal rearrangements in nine steps in the total yield of 9 and 17 , respectively (Cheng and Zhou 1993b) (Scheme 12). The initial step of the synthesis involved the conversion of stevioside (2) to 126. Compound 126 was rearranged to 127 by treatment with BF3-OEt2 which was mesylated to give 128....

Synthesis of erythroxydiol A hydroxymotiogynol

( )-Erythroxydiol A (hydroxymonogynol) (183), isolated from Erythroxylon monogynum, has been prepared from (-)-steviol (Mori and Matsui 1970 Mori et al. 1972) (Scheme 18). ( )-Steviol methyl ester (73) was oxidized with m-chloroperbenzoic acid in benzene-dioxane to give an epoxide 175, which was treated with a trace of HCl in aqueous acetone to afford a beyerane ketol, 176. Jones oxidation ofthe ketol 176 gave a keto acid 177, which was esterified with diazomethane to the corresponding methyl...

Synthesis of Methyl 7oxopodocarp8en16oate

Methyl ( )-7-oxopodocarp-8-en-16-oate (7), a key intermediate in the synthesis of steviol, has been produced synthetically (Mori and Matsui 1966) (Scheme 5). (57) was converted into the ester 58 by treatment with sodium ethoxide followed by methylation with iodomethane.Addition of -phenylethyl magnesium bromide to the keto ester 58 followed by dehydration of the resulting alcohol Scheme 5 Synthesis of methyl ( )-7-oxopodocarp-8-en-16-oate by Mori and Matsui. Scheme 5 Synthesis of methyl (...

Synthesis of sweettasting stevioside analogues by glycosidation

In an effort to discover sweet stevioside analogues, Esaki et al. (1984) and Kamiya et al. (1979) glycosidated steviolbioside (81) with various mono- and disaccharides (86 94) in the presence of silver carbonate-Celite in 1, 2-dichloroethane (Scheme 8). Their syntheses involved coupling reactions between hepta-O-acetyl steviolbioside with selected O-acetyl protected mono- or disaccharide halides which, after deacetylation, afforded the desired products (95 103). X...

Synthesis of sweettasting stevioside analogues with a sodiosulfopropyl group

Due to the potential acute toxicity of steviol (1) (Vignais et al. 1966) and the suggested possible breakdown of stevioside (2) to steviol in vivo and absorption of steviol through the gastrointestinal tract (Wingard et al. 1980), a series ofsodiosulfopropyl group-attached stevioside analogues, which retain the sweet taste of stevioside but are biologically stable, were prepared (DuBois et al. 1981 1984) (Scheme 10). The 19-O- -D-glucosyl moiety of stevioside (2) was replaced by a...

Transglucosylation

The above findings prompted us to try and improve the sweetness of stevioside (1) and its congeners by selectively adding sugar units to the C-13 sugar residues. Since stevioside is used as a food additive in Japan, non-synthetic biological (enzymatic) treatment was preferable. In the food industry, several glucosidases have been used to modify the structures of polysaccharides. Some of these enzymes not only hydrolyze but also transfer the sugar moieties to other molecules. For example,...

Triterpenoids And Steroids

The known triterpenoid -amyrin acetate (23) and three unidentified esters of lupeol were obtained from the ether-soluble portion of a methanolic extract of S. rebaudiana leaves (Sholichin Figure 4.4 Structures of triterpenes and sterols isolated from Stevia rebaudiana. Figure 4.4 Structures of triterpenes and sterols isolated from Stevia rebaudiana. et al. 1980). More recently, a lupeol ester, lupeol 3-palmitate (24), was identified from a methanolic extraction of S. rebaudiana by GC-MS...

Usa

First published 2002 by Taylor & Francis Simultaneously published in the USA and Canada 29 West 35th Street, New York, NY 10001 Taylor & Francis is an imprint of the Taylor & Francis Group This edition published in the Taylor & Francis e-Library, 2004. To purchase your own copy of this or any of Taylor & Francis or Routledge's collection of thousands of eBooks please go to www.eBookstore.tandf.co.uk. All rights reserved. No part of this book may be reprinted or reproduced or...

Volatile Oil Components

The volatile oils from the leaves and infloresences of S. rebaudiana have been studied, and a number of monoterpenes, sesquiterpenes, alkanols, aldehydes, and aromatic alcohols have been identified (Fujita et al. 1977 Martelli et al. 1985), as summarized in Table 4.2. Using GC-MS, Fujita et al. (1977) were able to identify 32 components of the essential oil of S. rebaudiana, including the sesquiterpenes -caryophyllene, trans- -farnesene, a-humulene, -cadinene, caryophyllene oxide, nerolidol,...

Zieglers approach toward the total synthesis of steviol

The total synthesis ofsteviol by Ziegler and Kloek (1971 1977) involved the stereocontrolled photo-addition of allene 29 to cyclopent-1-ene-1-carboxaldehyde 28 as the key synthetic step to establish C D ring structure 32 (Equation 6.2 and Scheme 3).Alkylation by potassium enolate of Hagemann's ester 36 with the mesylate of the m-methoxyphenylethyl alcohol 37 and subsequent decarboxylation afforded 38. The enone 38 was subjected to a phosphorus pentaoxide assisted cyclization to afford 39. A...

Preface to the series

There is increasing interest in industry, academia and the health sciences in medicinal and aromatic plants. In passing from plant production to the eventual product used by the public, many sciences are involved. This series brings together information which is currently scattered through an ever increasing number ofjournals. Each volume gives an in-depth look at one plant genus, about which an area specialist has assembled information ranging from the production of the plant to market trends...

Rubusoside and related glycosides from Rubus suavissimus

In a continuation oftheir search for natural sweeteners,Tanaka et al. (1981) isolated rubusoside (7 steviol 13,19-di-O- -D-glucoside) from the leaves of a type of the Chinese raspberry, R. suavissimus S.Lee (Rosaceae). Although Rubus is taxonomically distinct from Stevia (Compositae), the structure of 7 was identical with the intermediate obtained from the synthesis of rebaudioside A (2) from stevioside (1) (see Figure 7.2). Rubusoside (7) tastes sweet, but the magnitude of sweetness is not...

Sweetness quality

Figure 9.3 shows the sweetness-taste profiles of stevioside, rebaudioside A, and other sweeteners including saccharin, sucrose, and glycyrrhizin. When placed in the mouth, stevioside gives a slightly latent sweet sensation with an aftertaste. Nevertheless, the taste profile of stevioside more closely resembles that of sucrose compared with the triterpene glycoside sweetener, glycyrrhizin, and the sweetness quality of stevioside is superior to that of sucrose in mildness and freshness. The...

Relationship Between Stevia And

Through the ages, a relationship between man and Stevia plants has developed. Such a relationship took the form of recognition of the plants as expressed in their common names and the discovery of their utility in various ways.The knowledge discovered became part of the folklore of a culture or a population and, occasionally, came to the attention of botanists, explorers, or even casual travelers, who recorded it and communicated it in a written form. Some of the older records are not easy to...

Total synthesis of hibaene

Ireland and coworkers converted ketoacetal 149 to the hydroxy olefin 156, a model for the C D ring system of steviol (1) (Bell et al. 1966b). Acid-catalyzed rearrangement of 156 provided entry to the hibaene-stachene system, and the synthesis of racemic hibaene 158 was achieved (Scheme 15). Introduction of the C-13 acetyl grouping was accomplished through hydroboration-oxidation of the C-13 ethylene derivative 150 which in turn was obtained from the C-13 keto acetal 149 with...

Evaluation Of The Safety Of Stevioside In Korea

While there has been considerable doubt expressed on the safety of stevioside in Korea, as in several other countries, a recent report of the Korean Food and Hygienic Consideration Committee of the Ministry of Health and Welfare concluded provisionally that consumption of stevioside is regarded as safe for human health (Korea National Institute of Health 1996). In addition to stevioside, steviol, the aglycone of stevioside, has also been reported to have toxic effects (Pezzuto et al. 1985...

Total synthesis of kaurene and atisirene

The synthesis of ( )-kaurene (159) from the olefinic aldehyde 163 via hydroboration of the double bond and aldol-type cyclization of the C-14 ketoacetal 165 to form a bridged system has been reported (Bell et al. 1966a) (Scheme 17). The route makes available as well the substituted bicyclo 2.2.2 octane derivatives through similar cyclization of the isomeric C-13 ketoacetal 149 from the hydroboration and leads to ( )-atisirene (169). (i) ethylene glycol, TsOH, C6H6, reflux (II) BH3-THF, H202,0H_...

Chemical Constituents

Despite the fact that Stevia is one of the largest and most easily recognized genus in the tribe Eupatorieae (Robinson and King 1977), this morphologically well-delineated taxon in the Piqueria group is surprisingly diverse in its chemical composition. However, the chemical profile for Stevia does not differ widely from that described for other members of the Eupatorieae (Dom nguez 1977). To our knowledge, phytochemical information is available to date on only 58 species, with some of the...

Synthesis of radiolabeled gibberellic acids from steviol

Radiolabeled gibberellic acids from steviol have been prepared by feeding chemically synthesized radiolabeled steviol acetate (133) to the fungus Gibberella fujikuroi (Gianfagna et al. 1983) (Scheme 13). Steviol (1) was obtained by enzymatic hydrolysis ofstevioside (2) and the product was acetylated with acetic anhydride-pyridine under reflux.The resulting acetate 133 was oxidized with OsO4-NaIO4 to acid, 134. Labeled steviol acetate (135) was produced by theWittig reaction from 134 using 2H...

Recent Trnd In Cancer Madicine Of Stevioside

Akashi, H. (1975) Safety of dried-leaves extracts of stevia (report of toxicological test). Shokuhin Kogyo (Food Industry) 18, 1 4. Akashi, H. andYokoyama,Y. (1975) Dried-leaf extracts of Stevia. Toxicology tests. Shokuhin Kogyo (Food Industry) 18, 34-43. Alvarez, M., Bazzote, R.B., Godoy, G.L., Cury, R. and Espinoza, A.D. (1981) Hypoglycemic effect of Stevia rebaudiana Bertoni. Arquivos Biologia eTecnologia 24, 178. Bakal, A.I. and O'Brien Nabors, L. (1986) Stevioside. In Alternative...

Cultivation And Cell Culture Of Stevia Rebaudiana

There is now a considerable body of literature on methods for the cultivation of S. rebaudiana leaves leading to the optimization of levels of their sweet ent-kaurene glycoside constituents. The native habitat of S. rebaudiana is at a latitude of25 S in a subtropical region ofnortheastern Paraguay between 500 1,500 m above sea level, on soil having a low phosphate content, with an annual average temperature of75 F, and an average rainfall of about 55 in. per year (Sumida 1973 Shock 1982). This...

Moris approach toward the total synthesis of steviol

The total synthesis of steviol (1) by Mori (Mori and Matsui 1965 1966 1970 Mori et al 1970a 1970b Nakahara et al. 1971 Nakahara 1982) is described in Scheme 1.The synthesis involves the annelation of 6-methoxy-1-methyl-2-tetralone (4) with methyl acroylacetate (3) to afford 5. Compound 5 was methylated and converted to thioketal 6. Desulfurization of 6, followed by Birch reduction afforded an a, -unsaturated ketone (7). Compound 7 was selectively reduced with lithium tri-t-butoxyaluminum...

The Genus Stevia

Stevia is a New World genus distributed from the southern United States to Argentina and the Brazilian highlands, through Mexico, the Central American States, and the South American Andes. It is one of five large genera of the Eupatorieae, of which none has been fully monographed in recent years. These five genera are Ageratina, Chromolaena, Koanophyllon, Mikania, and Stevia (Robinson and King 1977 King and Robinson 1987). Members of Stevia comprise herbs and shrubs, found mostly at altitudes...

Transglycosylation by other enzyme systems

Trans-a-1,6- and 1,3-glucosylation by biozyme L and glucosyltransferase from Streptococcus mutans Aiming for a more effective transglucosylation system, several commercially available glucosyltransferases were screened.Treatment of stevioside (1) with maltose and 'Biozyme L' (a crude -amylase preparation produced by Aspergillus spp.) afforded three products (i) 1m (6-O-a-glucosylated at the C-19-O-glucose) (ii) 2m (6-O-a-glucosylated at C-13-O-glucose) and (iii) 3m (3-O-a-glucosylated at the...

Comparison Of Stevioside To Other Natural Product Highintensity Sweetening Agents

In 1998, the artificial sweetener market in the United States was worth about 610 million, and this is scheduled to increase 3.4 per year to 720 million by 2003 (Seewald 2000). There remains a strong demand for highly sweet, non-caloric, and non-cariogenic substances to substitute for sucrose in the diet. Such compounds, whether natural or synthetic, should exhibit a sucrose-like taste, and should also lack any offensive odor, exhibit satisfactory water solubility and hydrolytic and thermal...

CGTase and starch

Stevioside (1) was treated with the CGTase with soluble starch as donor, yielding a complex mixture of products which were mono-, di-, tri- and polyglucosylated at the 19-O-glucosyl unit and or the terminal glucosyl unit of the 13-O-sophorosyl moiety (Kasai et al. 1981) (Figure 7.6). Separation and structure identification ofall the mono- (S1a and S1b),di- (S2a, S2b, and S2c) and tri- (S3a, S3b, S3c, and S3d) glucosylated products were achieved by Fukunaga et al. (1989), who also evaluated the...

Conversion of stevioside to rebaudioside A

Rebaudioside A (108) is the sweetest of the ent-kaurene glycosides isolated from S. rebaudiana to date, being approximately 350 450 times sweeter than sucrose (Crammer and Ikan 1986). Stevioside (2) has been synthetically converted to rebaudioside A (108) (Kaneda et al. 1977) (Scheme 9).The synthetic pathway followed a selective removal ofa glucose unit from stevioside (2) at the C-13 position by an enzyme, and systematic reintroduction of two glucose units of different linkage to the remaining...

O

Figure 5.20 Structure of subpubescensoside (174) and the conformation of its aglycone. Figure 5.20 Structure of subpubescensoside (174) and the conformation of its aglycone. bitter-tasting principle was an acetylated ent-atisene diterpene glycoside, stevisalioside A (175). The structure was established by the interpretation ofspectral data, with the NMR assignments of this compound being based on 1H-1H COSY, 1H-13C HETCOR, and selective INEPT experiments. While acidic hydrolysis led to a...

Rubusoside as the starting material

Rubusoside (7), a congener of stevioside (1) with one less sugar unit, was also treated with the CGTase-starch system,to undergo trans-a-1,4-glucosylation. From the reaction mixture, mono- (R1a and R1b), di- (R2a, R2b, and R2c),tri- (R3a, R3b, R3c, and R3d) and three of five tetraglucosylated products (R4a, R4b, and R4e) were separated (Darise et al. 1984) and identified (Figure 7.8) (Ohtani et al. 1991a).Two of the tetraglucosylated products (R4c and R4d) were difficult to purify and were...

Acyclic and bicyclic diterpenoids

The aerial parts of S. myriadenia, the only species in the genus for which acyclic diterpenoids have been reported, were shown to contain geranyl-linalol (152) and 20-hydroxygeranylnerol (153), as well as several kaurene derivatives and bicyclic diterpenoids (Bohlmann et al. 1982). Examples of both enantiomeric series of the labdane skeleton, i.e. the 10-Mea-labdane and the enantiomeric 10-Me -labdane, have been described in Stevia. The normal labdane type has been found in the isolated...

Species Relationships In Stevia

Although sound phylogenetic relationships can be established only following a thorough systematic study of the genus, a discussion on relationships of species and subgeneric groups based on currently available data, and with emphasis on chemotaxonomic relationships, will provide guidance in continuing and future efforts to search for sweet-tasting molecules within the genus. On the basis of information available to him, Grashoff (1972) postulated two hypotheses for the origin and evolution of...

Tetracyclic diterpenoids

The genus Stevia is well-known as the source of eight important sweet-tasting ent-kaurene glycosides (Figure 5.18), namely, stevioside (161), steviolbioside (162), rebaudiosides A E (163 167), and dulcoside A (168), which are extracted commercially from the South American plant, S. rebaudiana (Ishikawa 1991). However, such sweet glycosides appear to have a very limited distribution in Stevia, since aside from S. rebaudiana, they were only detected in S. phlebophylla, among 108 other Stevia...

Analytical methods for steviol glycosides in stevia sweeteners

According to the Voluntary Specifications of Non-chemically Synthesized Food Additives (Second Edition 1993), the quantitative analysis oftotal steviol glycosides in stevia extracts is performed using high-performance liquid chromatography (HPLC) on an NH2 column (normal-phase mode), in the following manner. About 60 to 120 mg of the sample is accurately weighed and dissolved in 80 (v v) acetonitrile to make 100ml of a test solution. About 50 mg each of stevioside and rebaudioside A, dried...

Classification Of Stevia

Members of Stevia are characterized by the following. Plant habit Annual, perennial or rhizomatous perennial herbs or shrubs. Leaves Simple, opposite, rarely alternate, mostly petiolate, but exstipulate, penninerved or reticulately nerved. Inflorescences Capitula (flower heads) are arranged on a corymbose, paniculate or thyrsoid clusters at tips of branches or stem. Capitulum The capitulum consists of a cylindrical to funnelform involucre of five linear to oblong phyllaries (bracts) arranged in...

Medicinal and Aromatic Plants Industrial Profiles

Individual volumes in this series provide both industry and academia with in-depth coverage of one major medicinal or aromatic plant of industrial importance. Edited by Dr Roland Hardman Volume 1 Valerian, edited by Peter J.Houghton Volume 2 Perilla, edited by He-ci Yu, Kenichi Kosuna and Megumi Haga Volume 3 Poppy, edited by Jen Bernath Volume 4 Cannabis, edited by David T.Brown Volume 5 Ergot, edited by Vladimir Kren and Ladislav Cvak Volume 7 Caraway, edited by Eva Nemeth Volume 8 Saffron,...

Stevia extract

Soon after being introduced to the Japanese market, a simple, concentrated product of an aqueous decoction of S. rebaudiana leaves was employed, namely, 'stevia extract'. At present 'stevia extract' is made through several steps using absorbent resins to produce a white to pale yellowish powder or granule, containing stevioside, rebaudioside A, rebaudioside C, dulcoside A, and minor principles. According to the Voluntary Specifications of Non-chemically Synthesized Food Additives, published by...

Historical Perspective And Introduction

There can have been few botanical discoveries quite so dramatic as the realization that the leaves of Stevia rebaudiana (Bertoni) Bertoni (Compositae) are so highly sweet. It is not clear when this was made originally, but the observation was brought to the attention of the scientific community about a hundred years ago (Gosling 1901 Bertoni 1905 Lewis 1992). The British Consul at Asunci n, Paraguay, Cecil Gosling, attributed the discovery of the sweetness of the plant S. rebaudiana to the...

Practical Applications Of Stevia Sweeteners

Formulations of orange juice and coffee-flavored jelly containing a simple 'stevia extract' known as Marumilon Pure (Maruzen Pharmaceuticals Co. Ltd.), which is 200 times sweeter than sucrose, are shown in Table 9.6. In both examples, the amounts of Marumilon Pure to be added are 0.008 (w v) and 0.0184 (w w), respectively, of the formulations, and the sweetener substitutes for about 20 of the commonly used sugar in these foods. Stevia Table 9.6 Formulation of orange juice, coffee-flavored...

Pharmacological actions Energy metabolism

Steviol inhibits oxidative phosphorylation, with 40 M producing 50 inhibition (Vignais et al. 1966). It is, therefore, more potent than the related aglycones atractyligenin and dihydrosteviol (see Figure 8.1), which produce 50 inhibition at 210 M and 100 M, respectively. Some of the mitochondrial actions of steviol are summarized on Table 8.1. The effects on oxidative phosphorylation are complex, involving at least three components (i) inhibition of adenine nucleotide exchange (ii) inhibition...

Background To Stevia Sweetener Development In Japan

Stevia sweeteners in Japan were originally developed as alternative sweeteners for Japanese seasonings. Used in various Japanese foods for several hundred years, soy sauce is the most popularJapanese seasoning and is generally formulated with high levels ofsalt (sodium chloride) for preservation and flavoring. In the early part of the twentieth century, the suppressing effect of a decoction from roots of Glycyrrhiza species (licorice) on the saline taste of soy sauce was recognized. Since then,...

Essential Oils And Other Volatile Constituents

Although the flowers and leaves of Stevia species could be rich sources of essential oils, as expected for any member of the Asteraceae (Dom nguez 1977), only three studies have been carried out to fully analyze the lower terpenoids and volatile substances by modern techniques. The first study involved the gas chromatographic analysis of the essential oil of S. satureiaefolia, collected in Argentina, which yielded the monoterpenes borneol (1), cineole (2), pulegone (3), geraniol (4), nerol (5),...

Use Of Stevioside In Korea

Stevioside occupies 40 of the sweetener market in Korea (Seon 1995).Table 10.1 shows the increasing consumption of stevioside in Korea over the period 1988 1991. Presently, the majority of the S. rebaudiana leaves for the isolation of stevioside are imported from the People's Republic of China. Five companies in Korea manufacture stevioside from S. rebaudiana leaves and products containing this sweet compound. The total output of stevioside per year in Korea is estimated to be 200 250 metric...

Ethnobotany Of Steviarebaudiana

Although data on the ethnobotany of S. rebaudiana are givenin Table3.1, becauseofthe importance of this species, and because of in its native land, Paraguay (Soejarto et al. 1983a), furthercommentsconcerningthisspecies arejustified. The oldest record that points out the sweet-tastingpropertiesof S. rebaudiana isapaper by Mois s S.Bertoni published in Revista de Agronom ade Asunci n, vol. 1 35, 1899 (notseen by the author), when he described this species under the name of Eupatorium rebaudianaum...

Definition And Standardization Of Stevioside In Korea

Stevioside is defined as those compounds having the skeleton of steviol originating from S. rebaudiana, by the Korean Standard of Food Additives published by the Ministry of Health and Welfare (Ministry of Health and Welfare 1996). In addition to this definition, the product must contain 98.0 of stevioside (C38H60O18) as the major component by quantitative analysis, after being dried for two hours at 100 C. Stevioside is permitted as a food additive in distilled liquors, unrefined rice wines,...

Triterpenoids And Sterols

Besides the widespread sterols, -sitosterol, stigmasterol, and campesterol, Stevia species also produce pentacyclic triterpenoids with the oleanane, lupane, taraxastane and friedelane skeletons Figure 5.22 Selected kaurenoic and beyerenic acids derivatives 177 180 from Stevia species. Figure 5.22 Selected kaurenoic and beyerenic acids derivatives 177 180 from Stevia species. Figure 5.23 . -Amyrin 181, R1 H R2 CH3 , oleanolic acid 181, R1 H, R2 CO2H and their acetyl derivatives have been...

Physical Properties Solubility And Stability Of Stevioside

In pure form, stevioside acid -D-glucopyranosyl ester Chemical Abstracts name is a white crystalline material with a melting point of 198 C, an optical rotation of -39.3 in water, an elemental composition of C38H60O18, and a molecular weight of 804.88 Anonymous 1996 . Stevioside is only sparingly soluble in water 1 g dissolves in 800 ml water , but it is soluble in dioxane and slightly soluble in ethanol Anonymous 1996 . Rebaudioside A mp 242 244 C a D24 Table 1.3 Physical and solubility data...