| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1348134 | Tetrahedron: Asymmetry | 2007 | 19 Pages |
The dipolar cycloaddition of (Z)-N-benzyl-(3-O-benzyl-1,2-O-isopropylidene-α-d-ribofuranos-5-ylidene)amine N-oxide to methyl acrylate gives a 53:16:26:5 diastereomeric mixture of isoxazolidine derivatives. The dipolar cycloaddition of the xylo analogue to methyl acrylate is more diastereoselective, producing a 44:13:43 mixture of only three diastereomers. The ribo-configured adducts have been converted (4 steps only) into the new (2R,6S,7S,8R,8aR)-, (2S,6S,7S,8R,8aR)-, (2S,6S,7S,8R,8aS)- and (2R,6S,7S,8R,8aS)-2,6,7,8-tetrahydroxyindolizidines. Similarly, the two xylo-configured major isoxazolidine derivatives were converted into the known derivatives (2R,6S,7R,8R,8aS)- and (2S,6S,7R,8R,8aR)-2,6,7,8-tetrahydroxyindolizidines. The six isomeric indolizidine derivatives obtained have been evaluated for their inhibiting activities towards 15 glycosidases. Only the (2R,6S,7S,8R,8aR)-configured isomer is a selective inhibitor of amyloglucosidases from Aspergillus niger (IC50 = 350 μM) and from Rhizopus mold (IC50 = 90 μM, Ki = 195 μM, non-competitive), the other indolizidines show very little inhibitory activity at 1 mM concentration.
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(3R,5R)-1-Benzyl-5-(3-O-benzyl-1,2-O-isopropylidene-α-d-ribo-tetrofuranos-4-yl)-3-hydroxy-2-oxopyrrolidineC25H29NO6[α]D26=+52.9 (c 0.50, CH2Cl2)Source of chirality: (Z)-N-benzyl-(3-O-benzyl-1,2-O-isopropylidene-α-d-ribofuranos-5-ylidene)amine N-oxide and asymmetric synthesisAbsolute configuration: (3R,5R,1′R,2′R,3′R,4′R) assigned by X-ray crystallographic analysis
(3R,5R)-5-(3-O-Benzyl-1,2-O-isopropylidene-α-d-ribo-tetrofuranos-4-yl)-3-hydroxy-2-oxopyrrolidineC18H23NO6[α]D26=+16 (c 1.0, CH2Cl2)Source of chirality: (Z)-N-benzyl-(3-O-benzyl-1,2-O-isopropylidene-α-d-ribofuranos-5-ylidene)amine N-oxide and asymmetric synthesisAbsolute configuration: (3R,5R,1′R,2′R,3′R,4′R)
(3S,5S)-1-Benzyl-5-(3-O-benzyl-1,2-O-isopropylidene-α-d-ribo-tetrofuranos-4-yl)-3-hydroxy-2-oxopyrrolidineC25H29NO6[α]D26=+34.8 (c 0.325, CH2Cl2)Source of chirality: (Z)-N-benzyl-(3-O-benzyl-1,2-O-isopropylidene-α-d-ribofuranos-5-ylidene)amine N-oxide and asymmetric synthesisAbsolute configuration: (3S,5S,1′R,2′R,3′R,4′R) assigned by X-ray crystallographic analysis
(3S,5S)-5-(3-O-Benzyl-1,2-O-isopropylidene-α-d-ribo-tetrofuranos-4-yl)-3-hydroxy-2-oxopyrrolidineC18H23NO6[α]D26=+36 (c 1.0, CH2Cl2)Source of chirality: (Z)-N-benzyl-(3-O-benzyl-1,2-O-isopropylidene-α-d-ribofuranos-5-ylidene)amine N-oxide and asymmetric synthesisAbsolute configuration: (3S,5S,1′R,2′R,3′R,4′R)
(2R,4R)-1-Benzyl-2-(3-O-benzyl-1,2-O-isopropylidene-α-d-ribo-tetrofuranos-4-yl)-4-hydroxypyrrolidineC25H31NO5[α]D26=+73 (c 1.0, CH2Cl2)Source of chirality: (Z)-N-benzyl-(3-O-benzyl-1,2-O-isopropylidene-α-d-ribofuranos-5-ylidene)amine N-oxide and asymmetric synthesisAbsolute configuration: (2R,4R,1′R,2′R,3′R,4′R)
(2R,4S)-1-Benzyl-2-(3-O-benzyl-1,2-O-isopropylidene-α-d-ribo-tetrofuranos-4-yl)-4-hydroxypyrrolidineC25H31NO5[α]D26=+13.1 (c 1.5, CH2Cl2)Source of chirality: (Z)-N-benzyl-(3-O-benzyl-1,2-O-isopropylidene-α-d-ribofuranos-5-ylidene)amine N-oxide and asymmetric synthesisAbsolute configuration: (2R,4S,1′R,2′R,3′R,4′R)
(2S,4S)-1-Benzyl-2-(3-O-benzyl-1,2-O-isopropylidene-α-d-ribo-tetrofuranos-4-yl)-4-hydroxypyrrolidineC25H31NO5[α]D26=+13 (c 0.3, CH2Cl2)Source of chirality: (Z)-N-benzyl-(3-O-benzyl-1,2-O-isopropylidene-α-d-ribofuranos-5-ylidene)amine N-oxide and asymmetric synthesisAbsolute configuration: (2S,4S,1′R,2′R,3′R,4′R)
(2S,4R)-1-Benzyl-2-(3-O-benzyl-1,2-O-isopropylidene-α-d-ribo-tetrofuranos-4-yl)-4-hydroxypyrrolidineC25H31NO5[α]D26=+4 (c 0.25, CH2Cl2)Source of chirality: (Z)-N-benzyl-(3-O-benzyl-1,2-O-isopropylidene-α-d-ribofuranos-5-ylidene)amine N-oxide and asymmetric synthesisAbsolute configuration: (2S,4R,1′R,2′R,3′R,4′R)
(2R,6S,7S,8R,8aR)-2,6,7,8-TetrahydroxyindolizidineC8H15NO4[α]D26=-0.4 (c 0.75, CH3OH)Source of chirality: (Z)-N-benzyl-(3-O-benzyl-1,2-O-isopropylidene-α-d-ribofuranos-5-ylidene)amine N-oxide and asymmetric synthesisAbsolute configuration: (2R,6S,7S,8R,8aR)
(2S,6S,7S,8R,8aR)-2,6,7,8-TetrahydroxyindolizidineC8H15NO4[α]D26=+0.2 (c 1.35, CH3OH)Source of chirality: (Z)-N-benzyl-(3-O-benzyl-1,2-O-isopropylidene-α-d-ribofuranos-5-ylidene)amine N-oxide and asymmetric synthesisAbsolute configuration: (2S,6S,7S,8R,8aR)
(2S,6S,7S,8R,8aS)-2,6,7,8-TetrahydroxyindolizidineC8H15NO4[α]D26=+0.2 (c 0.5, CH3OH)Source of chirality: (Z)-N-benzyl-(3-O-benzyl-1,2-O-isopropylidene-α-d-ribofuranos-5-ylidene)amine N-oxide and asymmetric synthesisAbsolute configuration: (2S,6S,7S,8R,8aS)
(2R,6S,7S,8R,8aS)-2,6,7,8-TetrahydroxyindolizidineC8H15NO4[α]D26=-1.2 (c 1.0, CH3OH)Source of chirality: (Z)-N-benzyl-(3-O-benzyl-1,2-O-isopropylidene-α-d-ribofuranos-5-ylidene)amine N-oxide and asymmetric synthesisAbsolute configuration: (2R,6S,7S,8R,8aS)
(2R,4R)-2-(3-O-Benzyl-1,2-O-isopropylidene-α-d-ribo-tetrofuranos-4-yl)-4-hydroxypyrrolidineC18H25NO5[α]D26=+82.3 (c 0.875, CH2Cl2)Source of chirality: (Z)-N-benzyl-(3-O-benzyl-1,2-O-isopropylidene-α-d-ribofuranos-5-ylidene)amine N-oxide and asymmetric synthesisAbsolute configuration: (2R,4R,1′R,2′R,3′R,4′R)
(2R,4R)-2-(3-O-Benzyl-1,2-O-isopropylidene-α-d-ribo-tetrofuranos-4-yl)-1-benzyloxycarbonyl-4-hydroxypyrrolidineC26H31NO7[α]D26=+44.7 (c 0.45, CH2Cl2)Source of chirality: (Z)-N-benzyl-(3-O-benzyl-1,2-O-isopropylidene-α-d-ribofuranos-5-ylidene)amine N-oxide and asymmetric synthesisAbsolute configuration: (2R,4R,1′R,2′R,3′R,4′R)
(3S,5R)-5-(3-O-Benzyl-1,2-O-isopropylidene-α-d-xylo-tetrofuranos-4-yl)-3-hydroxy-2- oxopyrrolidineC18H23NO6[α]D26=-109 (c 0.875, CH2Cl2)Source of chirality: (Z)-N-benzyl-(3-O-benzyl-1,2-O-isopropylidene-α-d-xylofuranos-5-ylidene)amine N-oxide and asymmetric synthesisAbsolute configuration: (3S,5R,1′R,2′R,3′S,4′R)
(2R,4R)-2-(3-O-Benzyl-1,2-O-isopropylidene-α-d-xylo-tetrofuranos-4-yl)-4-hydroxypyrrolidineC18H25NO5[α]D26=-40 (c 0.2, CH2Cl2)Source of chirality: (Z)-N-benzyl-(3-O-benzyl-1,2-O-isopropylidene-α-d-xylofuranos-5-ylidene)amine N-oxide and asymmetric synthesisAbsolute configuration: (2R,4R,1′R,2′R,3′S,4′R)
(2R,4S)-2-(3-O-Benzyl-1,2-O-isopropylidene-α-d-xylo-tetrofuranos-4-yl)-4-hydroxypyrrolidineC18H25NO5[α]D26=-31.7 (c 0.45, CH2Cl2)Source of chirality: (Z)-N-benzyl-(3-O-benzyl-1,2-O-isopropylidene-α-d-xylofuranos-5-ylidene)amine N-oxide and asymmetric synthesisAbsolute configuration: (2R,4S,1′R,2′R,3′S,4′R)
