Steviol

Stevioside and rebaudioside A are diterpene glycosides. The sweetness is tainted with a bitter and undesirable aftertaste. The time—intensity profile is characteristic of naturally occurring sweeteners slow onset but lingering. The aglycone moiety, steviol [471 -80-7] (10), which is the principal metaboHte, has been reported to be mutagenic (79). Wide use of stevia ia Japan for over 20 years did not produce any known deleterious side effects. However, because no food additive petition has been presented to the FDA, stevioside and related materials caimot be used ia the United States. An import alert against stevia was issued by the FDA ia 1991. In 1995, however, the FDA revised this import alert to allow the importation and use of stevia as a diet supplement (80), but not as a sweetener or an ingredient for foods. Several comprehensive reviews of stevia are available (81,82). 

The only information available on taste-structure relationships is that the D-glucopyranosyl group seems to be essential for sweetness, as steviol sophoroside is not sweet. ... 

Upon utilization of 50% aq. acetone in the presence of 2,6-lutidine as a solvolytic medium, the mesylate (230) underwent rearrangement to give the methyl ester of (+)-steviol (231) in only 3 % yield 77). 

In Ziegler and Kloek s synthesis of ( )-steviol methyl ester, irradiation of hydrin-denal 17 and 1,2-propadiene (1) afforded the photocycloadduct 18 in 45% yield as a 14 1 mixture of diastereomers (Scheme 19.4) [6]. The major cycloadduct was subsequently converted to ( )-steviol methyl ester via a reduction of the aldehyde, followed by mesylation of the resulting alcohol and treatment with aqueous acetone in 2,6-lutidine. Unfortunately, steviol methyl ester (19) was obtained in only 3% yield. 

The reaction of steviol norketone (28) with [3H]methyltriphenylphosphonium bromide in the presence of potassium t-butoxide (Scheme 7) has been used in the... 

Chatsndthipong V, Jntabha P. (2001) Effect of steviol on para-aminohippu-rate transport by isolated perfnsed rabbit renal proximal tnbnle. J Pharmacol 298 1120-1127. 

Mosettig and Ness determined that steviol and isosteviol were diterpenoid acids with the former containing a 2,11-cyclopentanoperhydro-phenanthrene skeleton, a hydroxyl acid and a terminal methylene group. It was in 1963 that Mosettig and his colleagues finally showed the unambiguous structure of stevioside. 

Saponification of stevioside with a strong alkaline base yielded steviol-bioside. Although steviolbioside has been identified in some S. rebaudiana extracts, it is generally thought to be an artifact of extraction or isolation procedures rather than a naturally occurring glycoside. ... 

Glycoside Bioprocessing in Food and Flavor Chemistry 4.1 Steviol Glycosides... 

The leaves of Stevia rebaudiana (Compositae) are a source of several sweet glycosides of steviol (26) (Fig. 15) [1, 61]. The major glycoside, stevioside (27), is used in oriental countries as a food sweetener and the second major glycoside named rebaudioside (28), which is sweeter and more delicious than stevioside, is utilized in beverages. 

Fig. 15 Structures of steviol glycosides - for their relative sweetness see Table 1...

C. M. Compadre, et al. Characterization of bacterial mutagenicity mediated by 13-hydroxy-ent-kaurenoic acid CA142 (steviol) and several structurally related derivatives and evaluation of potential to induce glutathione-S-transferase in mice. Mutat Res 1986 169 93-103. 

The full paper has appeared on a synthesis of steviol. The route was based on the stereocontrolled photoaddition of allene to the cyclopentene-1-aldehyde (178), reduction of the aldehyde, and then solvolysis of the methanesulphonate (179). Papers on the synthesis of the aromatic ether (180) and on the construction of the c/d ring system of the alkaloid chasmanine " have been published. 

C Toskulkao, L Chaturat, P Temcharoen, T Glinsukon. Acute toxicity of stevioside, a natural sweetener, and its metabolite, steviol, in several animal species. Drug Chem Toxicol 20( 1—2) 31—44, 1997. 

The metabolism of stevia and stevia extracts has been the subject of much discussion. The available data are inconsistent and it is unclear whether steviol, the aglycone portion of stevioside, is generated in the gut. Steviol produces a mutagen (Phillips, 1987). The generation of steviol has been demonstrated in vitro and in vivo in rats (Phillips, 1987). 

Figure 4. Metabolites from feeds of steviol (ent-13-hydroxykaurenoic acid) and ent-kaurenoic acid to the GA mutant Bl-41a of G. fujikuroi. Steviol is found as a glucoside in the higher plant Stevia rebaudiana it is not found in the fungus.

The metabolism of steviol to 13-hydroxylated ent-gibberel-lanes and ent-kauranes." Phytochemistry, 1975, 14, 1741-1748. 

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