29 RECONSTRUCTION OF THE CARBOHYDRATE UNIT OF STEVIOSIDE
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Stevioside, a naturally occurring sweet substance, was isolated in 1931 from Stevia rebaudiana Bertoni. Synthesis of steviol (3), the aglycon part, has already been achieved. In order to complete the total synthesis of stevioside (1), we have studied the reconstruction of the carbohydrate unit of this molecule. Since the availability of synthetic steviol as the starting material for the further transformations is limited, chemical degradation of stevioside into steviol was first studied. Thus, NaIO_4 oxidation of stevioside and subsequent treatment of the product with base afforded a high yield of steviol. The glycosidation of steviol methyl ester, readily prepared from steviol by the treatment with diazomethane, by the use of heptaacetyl sophorosylbromide gave, after saponification, α- and β-sophoroside 17 and 8 in 86% and 3.1% yields respectively. Treatment of 8 with n-PrSLi afforded steviol bioside (5). Formation of the glycosyl ester linkage in stevioside was achieved in a following manner. Steviol bioside (5) was first transformed into tributyl stannylester (7). The reaction of acetobromoglucose with 7 and subsequent deacetylation afforded stevioside and its α-anomer in 61% and 23% yields respectively. Thus, we could complete the total synthesis of stevioside in seven steps starting from steviol, which in turn had been synthesized from cyclohexanone in 26 steps. In order to achieve a stereocontrolled β-glycosidation at tertiary ca alcohol, α stepwise approach to sophoroside part is also examined.
