Asymmetric synthesis of fagomine

We report an asymmetric synthesis of the alkaloid fagomine, which is an inhibitor of mammalian α-glucosidase and β-galactosidase, by means of Sharpless asymmetric dihydroxylation and Pd(II)-catalyzed cyclization, starting from 3-(t-butoxylcarbonylamino)propanol.

Figure optionsDownload as PowerPoint slide

(2R,3R)-5-[N-(tert-Butoxycarbonyl)amino]-2,3-dibenzyloxypentan-1-olC24H33O5NEe = 74% (det. by 1H NMR of O-methylmandelate ester)[α]D24=+16.8 (c 0.25, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R)

(4R,5R)-Ethyl-7-[N-(tert-butoxycarbonyl)amino]-4,5-dibenzyloxy-2-heptenateC28H37O6N[α]D24=+7.9 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4R,5R)

(4R,5R)-Ethyl-7-[N-(tert-butoxycarbonyl)amino]-4,5-dibenzyloxy-2-hepten-1-olC26H35O5N[α]D24=+14.0 (c 0.27, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4R,5R)

(2R,3R,4R)-N-tert-Butoxycarbonyl-3,4-dibenzyloxy-2-vinylpiperidineC26H33O4N[α]D24=-18.6 (c 0.85, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,4R)

(2R,3R,4R)-(N-tert-Butoxycarbonyl-3,4-dibenzyloxy-2-piperidinyl)-methanolC25H33O5N[α]D25-45.6 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,4R)

(2R,3R,4R)-3,4-Dibenzyloxy-1,5-imino-1,2,5-trideoxy-d-arabino hexitolC20H25O3N[α]D26=+11.6 (c 0.80, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,4R)

Fagomine, [1,5-imino-1,2,5-trideoxy-d-arabino hexitol]C6H13O3N[α]D27=+13.4 (c 0.86, H2O)Source of chirality: asymmetric synthesis