title: [Stereoselective synthesis of polyhydroxylated amines using (S)-pyroglutamic acid derivatives].
abstract: Naturally occurring polyhydroxylated amines such as (+)-1-deoxynojirimycin, polyoxamic acid, anisomycin, (-)swainsonine, and alexine stereoisomers, which have interesting biological activities including glucosidase- and mannosidase-inhibitory activity, immunoregulatory activity, and antibacterial effects, were synthesized stereoselectively starting from (S)-pyroglutamic acid derivatives. α,β-Unsaturated lactams ((S)-5-hydroxymethyl-2-oxo-3-pyrroline derivatives), α,β-unsaturated δ-lactone ((S)-4-amino-2-penten-5-olide derivative), and E-olefin ((S,E)-methyl-4-amino-5-hydroxypent-2-enoate derivative) from (S)-pyroglutamic acid derivatives were dihydroxylated using OsO4 in the presence of N-methyl morpholine N-oxide (NMO) to afford various chiral building blocks with different configurations. The stereoselectivity of cis-dihydroxylation for α,β-unsaturated lactams and α,β-unsaturated δ-lactone was very high, while the stereoselectivity was low for E-olefin. Therefore, the double asymmetric induction of E-olefin using K2OsO4 with chiral ligands was successively applied to yield high stereoselectivity. (2R,3S)-2-Hydroxymethyl-3-hydroxypyrrolidine and Gaissman-Weiss lactone, important intermediates for the preparation of pyrrolizidine alkaloids, were synthesized from a (3R,4R,5R)-3,4-dihydroxy-5-hydroxymethyl-2-pyrrolidinone derivative derived from α,β-unsatulated lactam. (+)-1-Deoxynojirimycin was synthesized from a (2S,3R,4R)-methyl 4-amino-2,3,5-trihydroxypentanoate derivative of E-olefin. (-)-Swainsonine and its stereoisomers were synthesized from (2R,3S,4R)- or (2R,3R,4R)-2-hydroxymethyl-3,4-dihydroxypyrrolidine derivatives of α,β-unsaturated δ-lactone or α,β-unsaturated lactam. The key reaction was diastereoselective allylation of the aldehyde derived from the corresponding 2-hydroxymethylpyrrolidine derivatives with various allylation reagents. The high diastereoselectivity could be explained by cyclic chelate formation between metals and the α-aminocarbonyl group or β-alkoxycarbonyl group, in which the nucleophile approaches from the less hindered face. Four alexine stereoisomers were synthesized from (2R,3R,4S,5R)- and (2R,3R,4S,5S)-2,3-dihydroxymethyl-3,4-dihydroxyl pyrrolidine derivatives of α,β-unsaturated lactam.
authors.affiliation: School of Pharmacy, Shujitsu University.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Ikota
mesh_terms: D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis; D006900:Hydroxylation; D007783:Lactones / Q000737:chemistry; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives*; D013237:Stereoisomerism
chemical_list: D000588:Amines; D000900:Anti-Bacterial Agents; D007783:Lactones; D011761:Pyrrolidonecarboxylic Acid