Synthesis of naturally occurring iminosugars from D-fructose by the use of a zinc-mediated fragmentation reaction.
A short synthesis of 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) and a formal synthesis of australine are described. In both cases, D-fructose is employed as the starting material and converted into a protected methyl 6-deoxy-6-iodo-furanoside. Zinc-mediated fragmentation produces an unsaturated ketone which serves as a key building block for both syntheses. Ozonolysis, reductive amination with benzylamine and deprotection affords 1,4-dideoxy-1,4-imino-D-arabinitol in only 7 steps and 11% overall yield from D-fructose. Alternatively, reductive amination with homoallylamine, ring-closing metathesis and protecting group manipulations give rise to an intermediate which can be converted into australine in 3 steps. The intermediate is prepared by two different strategies both of which use a total of 9 steps. The first strategy utilizes benzyl ethers for protection of fructose while the second and more effective strategy employs an isopropylidene acetal.
Lauritsen
Anne
A
Center for Sustainable and Green Chemistry, Department of Chemistry, Building 201, Technical University of Denmark, Lyngby.
Madsen
Robert
R
D005632:Fructose / Q000737:chemistry*; D050111:Imino Sugars / Q000138:chemical synthesis*; D013058:Mass Spectrometry; D015032:Zinc / Q000737:chemistry*
D050111:Imino Sugars; D005632:Fructose; D015032:Zinc