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Synthesis of Branched-Chain Nitro Sugars

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Description: Stereoselective synthetic approaches to the branched-chain nitro sugars sc D -rubranitrose, sc D -kijanose, and sc L -decilonitrose are described. These three nitro sugars are components of naturally occurring antibiotics and antitumor agents. The most critical part of the synthetic strategy for the synthesis of the nitro sugars is control of the stereochemistry of the geminally substituted C -3 carbon which bears methyl and nitro groups. It was discovered that geminal nitro methyl substitution could be introduced stereoselectively, through the intramolecular cyclization of allylic imidates derived from unsaturated carbohydrates and trichloroacetonitrile or dimethylcyanamide. This method provides a general route to cis 1,2-amino alcohols from allylic alcohols. It is especially useful in carbohydrate systems because cyclization of the imidates occur with predictable regio- and stereochemistry. Highly stereoselective syntheses of the three nitro sugars were developed using this method. Methyl $\alpha$- sc D -rubranitroside and methyl $\alpha$- sc D -kijanoside were synthesized from methyl $\alpha$- sc D -mannopyranoside in seventeen and fifteen steps respectively. In these syntheses it was demonstrated that dimethylcyanamide was a superior reagent, compared to trichloroacetonitrile, for the construction of cis 1,2-amino alcohols derived from the allylic alcohol methyl 2,3,6-trideoxy-3- C -methyl-$\alpha$- sc D - erythro -hex-2-enopyranoside. Methyl $\alpha$- sc L -decilonitroside was synthesized stereoselectively from di- O -acetyl- sc L -rhamnal in nine steps. The allylic alcohol methyl 2,3,6-trideoxy-3- C -methylene-$\alpha$- sc L - erythro -hexopyranoside reacted with dimethylcyanamide to form the desired allylic imidate, methyl 2,3,6-trideoxy-3- C -methylene-4- O -(N,N -dimethylamidino)-$\alpha$- sc L - erythro -hexopyranoside which after cyclization introduced the desired substitution with the correct stereochemistry at C -3.
Language: English
Format: Degree Work