Total synthesis of (+) methyl β-d-vicenisaminide

The total synthesis of methyl β-d-vicenisaminide 1 has been achieved. In this approach, the synthesis of enantiomerically pure methyl (4R,5S)- and (4S,5R)-4-azido-5-hydroxy-2(E)-hexenoates 2 was established by enzymatic resolution of (±)-anti-5-acetoxy -4-azido-2(E)-hexenoate 4. Another stereogenic center was introduced by base-catalyzed intramolecular conjugate addition of a hemiacetal-derived alkoxide nucleophile obtained by the reaction of methyl (4S,5R)-N-4-tert-butoxycarbonyl-N-methylamino-5-hydroxyl-2(E)-hexenoate 8 and benzaldehyde in the presence of a base.

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Methyl (4S,5R)-4-azido-5-hydroxy-2(E)-hexenoateC7H11N3O3[α]D23=+52.9 (c 0.82, CHCl3)Ee = >99%Source of chirality: lipaseAbsolute configuration: (4S,5R)

Methyl (4R,5S)-5-acetoxy-4-azido-2(E)-hexenoateC9H13N3O4[α]D23=-44.1 (c 0.78, CHCl3)Ee = >99%Source of chirality: lipaseAbsolute configuration: (4R,5S)

Methyl β-d-vicenisaminideC8H17NO3[α]D22=-3.7 (c 0.4, MeOH)Ee = >99%Source of chirality: lipaseAbsolute configuration: (2R,3R,4S,6R)