Title: Alternative Sweeteners

222 Kinghorn and Compadre
Figure 9 Structures of (a) perillaldehyde, (b) perillartine, and (c) SRI oxime V.
The intense sweetness and structural simplicity of perillartine have promoted
the synthesis of numerous analogs (1, 2, 57). This work has not only led
to a better understanding of the functional groups in compounds of the oxime
class that confer sweetness and bitterness, but has also led to the development
of several improved sweet compounds. One of the most promising of such derivatives
is SRI oxime V (Fig. 9). This compound is 450 times sweeter than sucrose
on a weight basis and exhibits much improved water solubility when compared
with perillartine.
SRI oxime V has no undesirable aftertaste and is stable above pH 3 (1, 2).
This substance was shown not to be a bacterial mutagen in the Ames assay and
exhibited an LD50 of 1 g/kg body weight in the rat after a single oral dose
(2). The compound is readily absorbed and metabolized, with excretion nearly
quantitative within 48 hr after administration to the rat, dog, and rhesus monkey.
The major metabolites of SRI oxime V were found to be products resulting from
the oxidation of either the methoxymethyl or the aldoxime moieties, as well as
those occurring after thioalkylation and glucuronidation (2). Subchronic toxicity
tests on this compound conducted in rats with a diet containing 0.6% SRI oxime
V for 8 wk revealed no apparent toxic effects. It has been suggested that SRI
oxime V shows such promise as an artificial sweetener that a chronic toxicity
evaluation is warranted (2).
B. Urea Derivatives
Dulcin (p-ethoxyphenylurea) has been known to be sweet for more than a century.
The compound is about 200 times sweeter than sucrose and was briefly
marketed as a sucrose substitute in the United States. Commercial use of this
compound was discontinued after it was found to be toxic to rats at a low dose.
Dulcin has also been found to be mutagenic (1, 2).
Another group of sweet ureas of more recent interest are the carboxylatesolubilized
p-nitrophenyl derivatives, which were discovered by Peterson and