Presentation Title

Enantioselective Total Synthesis of DAB-1

Start Date

November 2016

End Date

November 2016

Location

HUB 302-#144

Type of Presentation

Poster

Abstract

We are working towards the total synthesis of the iminosugar, DAB-1. Similar in structure to many cyclic carbohydrates, DAB-1 possesses a polyhydroxylated pyrrolidine core. DAB-1 acts as an α-glucosidase inhibitor that disrupts the metabolism of specific sugars in the body. DAB-1 has many interesting biological applications, most significantly, its potential interference with the production of HIV glycoproteins in infected cells. Our synthetic route constructs this stereogenic triol using an almond extracted enzyme on an inexpensive prochiral starting material. The primary goal is to isolate DAB-1 enantioselectively using the cyanide dependent almond enzyme, Oxynitrilase. Key transformations in the synthesis include an enzymatic induction of asymmetry, a ruthenium catalyzed cross metathesis, a palladium transposition, and a diastereoselective Sharpless dihydroxylation. Our asymmetric cyanation sets the first stereocenter with >95% enantiopurity and our palladium transposition occurs with high stereospecificity. We have optimized the completed steps in the synthetic pathway in modest to excellent yields and with a conservation of enantiomeric excess. An enantioenriched precursor to the pyrrolidine skeleton was recently isolated and current efforts are aimed at a cyanide assisted ring closing to form the gamma lactam. Reduction of the pyrrolidinone and cleavage of the benzyl ether will afford the complete synthesis of DAB-1. The versatility of our synthetic method will lead to future work focused on synthesizing medically significant analogs of DAB-1.

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Enantioselective Total Synthesis of DAB-1

HUB 302-#144

We are working towards the total synthesis of the iminosugar, DAB-1. Similar in structure to many cyclic carbohydrates, DAB-1 possesses a polyhydroxylated pyrrolidine core. DAB-1 acts as an α-glucosidase inhibitor that disrupts the metabolism of specific sugars in the body. DAB-1 has many interesting biological applications, most significantly, its potential interference with the production of HIV glycoproteins in infected cells. Our synthetic route constructs this stereogenic triol using an almond extracted enzyme on an inexpensive prochiral starting material. The primary goal is to isolate DAB-1 enantioselectively using the cyanide dependent almond enzyme, Oxynitrilase. Key transformations in the synthesis include an enzymatic induction of asymmetry, a ruthenium catalyzed cross metathesis, a palladium transposition, and a diastereoselective Sharpless dihydroxylation. Our asymmetric cyanation sets the first stereocenter with >95% enantiopurity and our palladium transposition occurs with high stereospecificity. We have optimized the completed steps in the synthetic pathway in modest to excellent yields and with a conservation of enantiomeric excess. An enantioenriched precursor to the pyrrolidine skeleton was recently isolated and current efforts are aimed at a cyanide assisted ring closing to form the gamma lactam. Reduction of the pyrrolidinone and cleavage of the benzyl ether will afford the complete synthesis of DAB-1. The versatility of our synthetic method will lead to future work focused on synthesizing medically significant analogs of DAB-1.