The first enantioselective synthesis of imino-deoxydigitoxose and protected imino-digitoxose by using l-threonine aldolase-catalyzed aldol condensation

The first enantioselective synthesis of protected imino-digitoxose (−)-16 was attained starting with a synthetic intermediate of polyoxin C prepared by the l-threonine aldolase-catalyzed aldol condensation of (2S,3S)-2,3-O-isopropyriden-4-penten-1-al 8 and glycine. The strategy took advantage of an intramolecular nucleophilic attack by a Cbz-protected amino group on the hemiacetal carbon, a side reaction in the synthesis of natural products, for the formation of the piperidine ring of the imino-sugar. Imino-deoxydigitoxose (+)-18 was also synthesized from (−)-16 by reduction and acid hydrolysis.

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Methyl (2S,3R,4S,5S)-2-N-carboxybenzylamido-3-hydroxy-4,5-O-isopropyriden-6-hepten-1-olC18H25O6N[α]D24=+6.8 (c 0.99, CHCl3)

(2S,3R,4S,5S)-2-N-Carboxybenzylamido-3-hydroxy-2,3/4,5-O,N-diisopropyriden-6-heptenyl-1-O-p-toluenesulfonylateC28H35O8NS[α]D26=-2.6 (c 0.94, CHCl3)

(2S,3R,4S,5S)-2-N-Carboxybenzylamido-3,4,5-triacetoxy-6-hepteneC21H27O8N[α]D27=+22.6 (c 0.95, CHCl3)

(2S,3R,4S,5S)-2-N-Carboxybenzylamido-3,4-diaccetoxy-6-hepteneC19H25O6N[α]D25=+24.0 (c 1.17, CHCl3)

5-N-Carboxybenzylamido-5,6-dideoxy-3,4-diacetoxy-d-allo-iminopyranosideC18H23O7N[α]D21=-26.4 (c 1.24, CHCl3)

5-N-Carboxybenzylamido-1,5,6-trideoxy-3,4-diacetoxy-d-allo-iminopyranosideC18H23O6N[α]D25=-56.9 (c 0.690, CHCl3)

5-N-Carboxybenzylamido-1,5,6-trideoxy-3,4-dihydro-d-allo-iminopyranoside hydrochlorideC6H14O2NCl[α]D25=+46.8 (c 0.86, MeOH)