On December 18, 2008, the Food and Drug Administration ruled the natural sweetener Truvia “generally safe” for use in foods and beverages. Truvia (trade name Rebiana) is comprised of a diterpene called steviol glycoside, which is isolated from the extracts of the leaves of the plant Stevia rebaudiana bertoni. The herb Stevia—basically the leaves of the plant—has been available for years, so steviol glycoside is nothing new, per se. Cargill Food and Ingredient Systems now markets Truvia as a singular, “fully-characterized product” (Stevia, by comparison is a witch’s brew of anywhere from 40 to 200 compounds). More interesting data about Truvia can be found here. As a result of the FDA’s ruling, Coca-Cola Company will soon launch a new line of reduced-calorie drinks with the most prominent being a new version of Sprite called Sprite Green (comes in a nifty aluminum can).
Stevia was purportedly discovered by Moises Santiago Bertoni in 1887 while exploring the forests of Paraguay—Stevia rebaudiana‘s natural habitat (see: Econ. Bot. 1983, 37, 74-82). Additionally, the plant had been identified in Korea, China and Japan (J. Med. Chem. 1981, 24, 1269–1271). Word spread about the plant and eventually Stevia made its way to the US (courtesy of the Department of Agriculture) in 1918 due to the growing interest in its strong sweetness. A wide array of physiological studies determined that the sweet sensation of Stevia derives from the presence the compound steviol glycoside. Since then, several studies have been reported on its structure and function of steviol glycoside including stereochemical analysis (J. Am. Chem. Soc. 1963, 85, 2305–2309) and metabolic analyses (J. Agric. Food Chem. 2006, 54, 2794–2798).
In the spirit the Truvia saga, I figured that I’d cover its first total synthesis of steviol methyl ester, which Mori and co-workers first reported (Tetrahedron Lett. 1970, 11, 2411-2414). Starting from the tricyclic methyl ester, Mori protected the aldehyde then installed ketone by way of a hydroboration-oxidation and ensuing Jones oxidation. Deprotection of the dioxolane was accomplished using aqueous acid in acetone followed by tandem acid-catalyzed aldol addition to furnish the 1,3-ketol, which was converted to the 1,3-dione via second Jones oxidation. Clemmenson reduction afforded the 1,2-ketol (I encourage you to push the arrows for that transformation), which was converted to the allylic alcohol by methylenation.
As is the case with most “new” sweeteners, Stevia has been the subject of criticism over toxicological effects. One study, conducted by John Pezzuto and co-workers at the University of Chicago, concluded that steviol is actually metagenic (PNAS 1985, 82, 2478-2482). However, the asterisk to this scientific study—“steviol is mutagenic toward S. typhimurium strain TM677” and not human cells—should clearly be taken into consideration when weighing the toxicity of the supplement as a whole. Just so we’re all on the same page, the “S” in “S. typhimurium” stands for salmonella—a bacterium.
All in all, I think it’ll pretty interesting to watch more information about Truvia find its way into the public eye.