A concise synthesis of (−)-lentiginosine via an anti,syn-oxazine

A concise and stereocontrolled total synthesis of (−)-lentiginosine, a potent glycosidase inhibitor, has been achieved. Starting from anti,syn-oxazine as a chiral building block, the key features in these strategies are the Wittig reaction and cyclization.

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(4R,5R,6R)-5-(tert-Butyldimethylsilyloxy)-4-((tert-butyldimethylsilyloxy)methyl)-2-phenyl-6-vinyl-5,6-dihydro-4H-1,3-oxazineC25H44NO3Si2[α]D25=+3.8 (c 1.0, CHCl3)Source of chirality: d-Serine and asymmetric synthesisAbsolute configuration: (4R,5R,6R)

(3R,4R,5R)-5-(Benzyloxycarbonylamino)-4,6-bis(tert-butyldimethylsilyloxy)hex-1-en-3-yl benzoateC33H51NO6Si2[α]D25=+39.6 (c 1.0, CHCl3)Source of chirality: d-Serine and asymmetric synthesisAbsolute configuration: (3R,4R,5R)

(3R,4R,5R)-4-(tert-Butyldimethylsilyloxy)-5-((tert-butyldimethylsilyloxy)methyl)pyrrolidin-3-yl benzoateC24H44NO4Si2[α]D25=-39.2 (c 1.0, CHCl3)Source of chirality: d-Serine and asymmetric synthesisAbsolute configuration: (3R,4R,5R)

(2R,3R,4R)-tert-Butyl 4-(benzoyloxy)-3-(tert-butyldimethylsilyloxy)-2-(hydroxymethyl)pyrrolidine-1-carb-oxylateC23H38NO6Si[α]D25=-15.3 (c 1.0, CHCl3)Source of chirality: d-Serine and asymmetric synthesisAbsolute configuration: (2R,3R,4R)

(2S,3R,4R)-tert-Butyl 2-((E)-4-(benzyloxy)but-1-enyl)-3-(tert-butyldimethylsilyloxy)-4-hydroxypyrrolidine-1-carboxylateC26H43NO5Si[α]D25=-18.8 (c 1.0, CHCl3)Source of chirality: d-Serine and asymmetric synthesisAbsolute configuration: (2S,3R,4R)

(2S,3R,4R)-tert-Butyl 3-(tert-butyldimethyl-silyloxy)-4-hydroxy-2-(4-hydroxybutyl)pyrrolidine-1-carboxy-lateC19H39NO5Si[α]D25=-18.0 (c 1.0, CHCl3)Source of chirality: d-Serine and asymmetric synthesisAbsolute configuration: (2S,3R,4R)

(1R,2R,8aR)-Octahydroindolizine-1,2-diolC8H16NO2[α]D25=-3.2 (c 1.0, CHCl3)Source of chirality: d-Serine and asymmetric synthesisAbsolute configuration: (1R,2R,8aR)