Isolation synthesis and glycosidase inhibition profile of 3-epi-casuarine

3-epi-Casuarine, the first naturally occurring stereoisomer of casuarine, was isolated from Myrtus communis L. The glycosidase inhibition profile and NMR spectra of 3-epi-casuarine are compared with those of casuarine; the change in configuration at one of the six stereogenic centres causes a dramatic change in the conformation of the bicyclic system. The key step in the 6% overall yield synthesis of 3-epi-casuarine from d-gluconolactone is the efficient cyclization of a completely unprotected pentahydroxyaminomesylate to the pyrrolizidine nucleus. A low yield synthesis of casuarine is also reported.

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Methyl 2-azido-2-deoxy-3,4:5,6-di-O-isopropylidene-d-mannonate 13C13H21N3O6Ee = 100%[α]D22=+21.5 (c 0.69, CHCl3)Source of chirality: d-glucono-1,5-lactone as starting material

Methyl 4-azido-5,6:7,8-di-O-isopropylidene-2,3,4-trideoxy-d-manno-oct-2-enoate 14C15H23N3O6Ee = 100%[α]D22=+35.5 (c 0.71, CHCl3)Source of chirality: d-glucono-1,5-lactone as starting material

4-Deoxy-2,3-di-O-tert-butyldimethylsilyl-5,6:7,8-di-O-isopropylidene-d-erythro-l-altro-octono-1,4-lactam 17C26H51NO7Si2Ee = 100%[α]D22=+1.8 (c 1.59, CHCl3)Source of chirality: d-glucono-1,5-lactone as starting material

4-Deoxy-2,3-di-O-tert-butyldimethylsilyl-5,6-O-isopropylidene-d-erythro-l-altro-octono-1,4-lactam 18C23H47NO7Si2Ee = 100%[α]D23=+2.9 (c 0.41, CHCl3)Source of chirality: d-glucono-1,5-lactone as starting material

4-Deoxy-5,6-O-isopropylidene-7-O-methanesulfonyl-2,3,8-tri-O-tert-butyldimethylsilyl-d-erythro-l-altro-octono-1,4-lactam 19C30H63NO9SSi3Ee = 100%[α]D23=+28.9 (c 0.37, CHCl3)Source of chirality: d-glucono-1,5-lactone as starting material

1,4-Dideoxy-1,4-imino-5,6-O-isopropylidene-7-O-methanesulfonyl-2,3,8-tri-O-tert-butyldimethylsilyl-d-erythro-l-altro-octitol 20C30H65NO8SSi3Ee = 100%[α]D24=-67.1 (c 0.38, CHCl3)Source of chirality: d-glucono-1,5-lactone as starting material

3-epi-Casuarine 1C8H15NO5Ee = 100%[α]D22=+5.8 (c 0.69, H2O)Source of chirality: d-glucono-1,5-lactone as starting material

4-Deoxy-5,6-O-isopropylidene-2,3,8-tri-O-tert-butyldimethylsilyl-d-erythro-l-altro-octono-1,4-lactam 22C29H61NO7Si3Ee = 100%[α]D23=+13.5 (c 0.65, CHCl3)Source of chirality: d-glucono-1,5-lactone as starting material

4-Deoxy-5,6-O-isopropylidene-2,3,8-tri-O-tert-butyldimethylsilyl-l-threo-l-altro-octono-1,4-lactam 24C29H61NO7Si3Ee = 100%[α]D23=+11.1 (c 0.55, CHCl3)Source of chirality: d-glucono-1,5-lactone as starting material

4-Deoxy-5,6-O-isopropylidene-7-O-methanesulfonyl-2,3,8-tri-O-tert-butyldimethylsilyl-l-threo-l-altro-octono-1,4-lactam 25C30H63NO9SSi3Ee = 100%[α]D22=+6.0 (c 0.57, CHCl3)Source of chirality: d-glucono-1,5-lactone as starting material

1,4-Dideoxy-1,4-imino-5,6-O-isopropylidene-7-O-methanesulfonyl-2,3,8-tri-O-tert-butyldimethylsilyl-l-threo-l-altro-octitol 26C30H65NO8SSi3Ee = 100%[α]D23=-8.5 (c 1.32, CHCl3)Source of chirality: d-glucono-1,5-lactone as starting material

Casuarine2C8H15NO5Ee = 100%[α]D23=+16.8 (c 0.33, H2O)Source of chirality: d-glucono-1,5-lactone as starting material