Carbon-branched δ-tetrahydrofuran sugar amino acids (SAAs) as dipeptide isostere scaffolds

The synthesis of the first branched sugar amino acid (SAA) scaffolds [methyl (3R,4R,5R)-5-azidomethyl-3,4-dihydroxy-tetrahydrofuran-3-carboxylate and methyl (3R,4R,5S)-5-azidomethyl-3,4-dihydroxy-tetrahydrofuran-3-carboxylate] by an efficient intramolecular displacement of a highly hindered neopentyl triflate allows access to enantiopure THF derivatives which have carbon substituents.

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5-Azido-5-deoxy-2,3-O-isopropylidene-D-lyxoseC18H13N3O4Ee 100%[α]D21=-36.0 (c 0.90, MeOH)Source of chirality: D-ribose as starting material

5-Azido-5-deoxy-2-C-hydroxymethyl-2,3-O-isopropylidene-d-riboseC9H15N3O5Ee 100%[α]D25=23.1 (c 0.95, MeCN)Source of chirality: d-ribose as starting material

5-Azido-5-deoxy-2-C-hydroxymethyl-2,3-O-isopropylidene-l-lyxoseC9H15N3O5Ee 100%[α]D22=-0.2 (c 0.96, CHCl3)Source of chirality: d-ribose as starting material

5-Azido-5-deoxy-2-C-hydroxymethyl-2,3-O-isopropylidene-d-ribono-1,4-lactoneC9H13N3O5Ee 100%[α]D25=+11.3 (c 0.31, MeCN)Source of chirality: d-ribose as starting material

5-Azido-5-deoxy-2-C-hydroxymethyl-2,3-O-isopropylidene-l-lyxono-1,4-lactoneC9H13N3O5Ee 100%[α]D21=-0.1 (c 0.73, CHCl3)Source of chirality: d-ribose as starting material

5-Azido-5-deoxy-2-C-hydroxymethyl-2,3-O-isopropylidene-2-C-trifluoromethanesulfonyl-d-ribono-1,4-lactoneC10H12F3N3O7SEe 100%[α]D21=+58.9 (c 0.52, CH2Cl2)Source of chirality: d-ribose as starting material

5-Azido-5-deoxy-2-C-hydroxymethyl-2,3-O-isopropylidene-2’-O-trifluoromethanesulfonyl-l-lyxono-1,4-lactoneC10H12F3N3O7SEe 100%[α]D21=-29.4 (c 0.70, EtOAc)Source of chirality: d-ribose as starting material

5-Azido-5-deoxy-2,3-O-isopropylidene-d-ribono-1,4-lactoneC8H11N3O4Ee 100%[α]D23=+18.9 (c 1.66, CHCl3)Source of chirality: d-ribose as starting material

5-Azido-5-deoxy-2,3-O-isopropylidene-l-lyxono-1,4-lactoneC8H11N3O4Ee 100%[α]D22=-75.8 (c 0.52, CHCl3)Source of chirality: d-ribose as starting material

Methyl (3R,4R,5R)-5-azidomethyl-3,4-dihydroxy-tetrahydrofuran-3-carboxylateC7H11N3O5Ee 100%[α]D21=+25 (c 4.4, MeOH)Source of chirality: d-ribose as starting material

Methyl (3R,4R,5R)-5-azidomethyl-3,4-dihydroxy-tetrahydrofuran-3-carboxylateC7H11N3O5Ee 100%[α]D21=-39.5 (c 0.61, MeOH)Source of chirality: d-ribose as starting material

5-Azido-5-deoxy-2-C-hydroxymethyl-2,3-O-isopropylidene-2-C-methoxymethyl-l-lyxono-1,4-lactoneC10H15N3O5Ee 100%[α]D23=-32.7 (c 0.22, CH2Cl2)Source of chirality: d-ribose as starting material

N-Benzyl 1,2′-anhydro-5-azido-5-deoxy-2-C-hydroxymethyl-2,3-O-isopropylidene-d-ribonamideC16H20N4O4Ee 100%[α]D23=+25.2 (c 1.76, MeCN)Source of chirality: d-ribose as starting material

1,2-Anhydro-2,3-O-isopropylidene-l-lyxofuranoseC8H12O4Ee 100%[α]D21=+106.8 (c 0.72, MeOH)Source of chirality: d-ribose as starting material