Stereocontrolled transformation of nitrohexofuranoses into cyclopentylamines via 2-oxabicyclo[2.2.1]heptanes. Part VI: Synthesis and incorporation of the novel polyhydroxylated 5-aminocyclopent-1-enecarboxylic acids into peptides

The first total synthesis of enantiopure methyl (3aR,4S,5S,6R,6aS)-4-benzyloxycarbonylamino-6-hydroxy-2,2-dimethyl-tetrahydro-3aH-cyclopenta[d][1,3]dioxole-5-carboxylate has been carried out according to our recent novel strategy for the transformation of nitrohexofuranoses into cyclopentylamines. This approach is based on an intramolecular cyclization that leads to 2-oxabicyclo[2.2.1]heptane derivatives. E1cb elimination of the methoxy substituent was observed when attempting to incorporate these β-amino acid into peptides. As a result, the synthesis and incorporation of the first polyhydroxylated 5-aminocyclopent-1-enecarboxylic acid into peptides were developed.

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6-O-tert-Butyldiphenylsylil-1,2-O-isopropylidene-3-O-methyl-α-d-glucofuranoseC26H36O6Si[α]D22=-44.6 (c 1.1, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1R,2R,3S,4R,5R)

5-O-Benzyl-6-O-tert-butyldiphenylsylil-1,2-O-isopropylidene-3-O-methyl-α-d-glucofuranoseC33H42O6Si[α]D24=-44.4 (c 1.0, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1R,2R,3S,4R,5R)

5-O-Benzyl-1,2-O-isopropylidene-3-O-methyl-α-d-glucofuranoseC17H24O6[α]D22=-35.7 (c 1.0, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1R,2R,3S,4R,5R)

5-O-Benzyl-6-deoxy-6-iodo-1,2-O-isopropylidene-3-O-methyl-α-d-glucofuranoseC17H23IO5[α]D22=-62.9 (c 1.0, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1R,2R,3S,4S,5S)

5-O-Benzyl-6-deoxy-1,2-O-isopropylidene-3-O-methyl-6-nitro-α-d-glucofuranoseC17H23NO7[α]D17=-46.7 (c 1.0, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1R,2R,3S,4R,5R)

5-O-Benzyl-6-deoxy-3-O-methyl-6-nitro-d-glucono-1,4-lactoneC14H17NO7[α]D25=+30.8 (c 1.4, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (2R,3R,4R,5R)

(1S,4S,5S,6R,7R)-6-Benzyloxy-7-methoxy-5-nitro-2-oxabicyclo[2.2.1]heptan-3-oneC14H15NO6[α]D24=-8.4 (c 1.2, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1S,4S,5S,6R,7R)

Methyl (3aR,4S,5S,6R,6aS)-4-benzyloxycarbonylamino-tetrahydro-6-hydroxy-2,2-dimethyl-3aH-cyclopenta[d][1,3]dioxole-5-carboxylateC18H23NO7[α]D23=+70.0 (c 1.0, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (3aR,4S,5S,6R,6aS)

Methyl (3aR,4S,5S,6R,6aS)-4-benzyloxycarbonylamino-tetrahydro-6-methoxy-2,2-dimethyl-3aH-cyclopenta[d][1,3]dioxole-5-carboxylateC19H25NO7[α]D17=-13.6 (c 1.5, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (3aR,4S,5S,6R,6aS)

(3aR,4S,6aS,E)-4-Benzyloxycarbonylamino-4,6a-dihydro-2,2-dimethyl-3aH-cyclopenta[d][1,3]dioxole-5-carboxylic acidC17H19NO6[α]D24=-12.6 (c 1.8, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (3aR,4S,6aS,E)

Methyl (3aR,4S,5S,6R,6aS)-4-(benzyloxycarbonylglycylamino)-tetrahydro-6-methoxy-2,2-dimethyl-3aH-cyclopenta[d][1,3]-dioxole-5-carboxylateC21H28N2O8[α]D15=-19.2 (c 1.3, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (3aR,4S,5S,6R,6aS)

Methyl 2-((3aR,4S,6aS,E)-4-(2-(benzyloxycarbonylglycylamino)acetamido)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxole-5-carbamido)acetateC22H27N3O8[α]D16=-10.3 (c 1.1, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (3aR,4S,6aS,E)