Structure and temperature controlled synthesis of novel thiazolidin-4-one derivatives bearing an azasugar

Novel thiazolidin-4-one linked pseudo-aza-disaccharides and thiazolidin-4-ones containing C-pseudo-aza-nucleosides were synthesized via a one-pot three component reaction. The former was synthesized stereoselectively by the tandem Staudinger/aza-Wittig/cyclization reaction of azasugar aldehyde 1, an azidosugar, and mercaptoacetic acid. The reaction was structure and temperature controlled, and could be performed stereospecifically under 40 °C. It was the first report of a stereospecific synthesis of thiazolidin-4-one linked derivatives. However, these derivatives were synthesized with low stereoselectivity by involving the condensation reaction of azasugar aldehyde 1, aniline, and mercaptoacetic acid.

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(3aR,6S,7R,7aS)-6-(Azidomethyl)-2,2-dimethylhexahydro-[1,3]dioxolo[4,5-c]pyridin-7-olC9H16N4O3[α]D25=+32.6 (c 1.0, CHCl3)Source of chirality: d-mannoseAbsolute configuration: (3aR,6S,7R,7aS)

(3aR,6S,7R,7aS)-tert-Butyl 6-(azidomethyl)-7-hydroxy-2,2-dimethyltetrahydro-[1,3]dioxolo[4,5-c]pyridine-5(6H)-carboxylateC14H24N4O5[α]D25=+28.4 (c 1.0, CHCl3)Source of chirality: d-mannoseAbsolute configuration: (3aR,6S,7R,7aS)

(R)-3-(((2R,3S,4R,5R)-3,4-Dihydroxy-5-methoxytetrahydrofuran-2-yl)methyl)-2-((2R,3S,4R)-3,4-dihydroxypyrrolidin-2-yl)thiazolidin-4-oneC13H22N2O7S[α]D25=+12.4 (c 1.0, MeOH)Source of chirality: d-mannose, d-ribose, and asymmetric synthesisAbsolute configuration: (2R,3S,4R,5R), (R)thiazolidin-4-one, (2R,3S,4R)

(S)-3-(((2R,3S,4R,5R)-3,4-Dihydroxy-5-methoxytetrahydrofuran-2-yl)methyl)-2-((2R,3S,4R)-3,4-dihydroxypyrrolidin-2-yl)thiazolidin-4-oneC13H22N2O7S[α]D25=-26.0 (c 1.0, MeOH)Source of chirality: d-mannose, d-ribose, and asymmetric synthesisAbsolute configuration: (2R,3S,4R,5R), (S)thiazolidin-4-one, (2R,3S,4R)

(R)-2-((2R,3S,4R)-3,4-Dihydroxypyrrolidin-2-yl)-3-(((2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6-methoxytetrahydro-2H-pyran-2-yl)methyl)thiazolidin-4-oneC14H24N2O8S[α]D25=+123 (c 1.0, MeOH)Source of chirality: d-mannose, d-glucose, and asymmetric synthesisAbsolute configuration: (2R,3S,4R), (R)thiazolidin-4-one, (2R,3S,4S,5R,6S)

(R)-2-((2R,3S,4R)-3,4-Dihydroxypyrrolidin-2-yl)-3-(((2S,3S,4R)-3,4-dihydroxypyrrolidin-2-yl)methyl)thiazolidin-4-oneC12H21N3O5S[α]D25=+31.1 (c 1.0, H2O)Source of chirality: d-mannose and asymmetric synthesisAbsolute configuration: (2R,3S,4R), (R)thiazolidin-4-one, (2S,3S,4R)

(R)-2-((2R,3S,4R)-3,4-Dihydroxypyrrolidin-2-yl)-3-(((2S,3R,4R,5R)-3,4,5-trihydroxypiperidin-2-yl)methyl)thiazolidin-4-oneC13H23N3O6S[α]D25=+55.4 (c 1.0, H2O)Source of chirality: d-mannose and asymmetric synthesisAbsolute configuration: (2R,3S,4R), (R)thiazolidin-4-one, (2S,3S,4R,5R)

(R)-2-((2R,3S,4R)-3,4-Dihydroxypyrrolidin-2-yl)-3-phenylthiazolidin-4-oneC13H16N2O3S[α]D25=+115.1 (c 1.0, MeOH)Source of chirality: d-mannose and asymmetric synthesisAbsolute configuration: (2R,3S,4R), (R)thiazolidin-4-one

(S)-2-((2R,3S,4R)-3,4-Dihydroxypyrrolidin-2-yl)-3-phenylthiazolidin-4-oneC13H16N2O3S[α]D25=-130.1 (c 1.0, MeOH)Source of chirality: d-mannose and asymmetric synthesisAbsolute configuration: (2R,3S,4R), (S)thiazolidin-4-one

(R)-3-(4-Chlorophenyl)-2-((2R,3S,4R)-3,4-dihydroxypyrrolidin-2-yl)thiazolidin-4-oneC13H15ClN2O3S[α]D25=+64.1 (c 1.0, MeOH)Source of chirality: d-mannose and asymmetric synthesisAbsolute configuration: (2R,3S,4R), (R)thiazolidin-4-one

(S)-3-(4-Chlorophenyl)-2-((2R,3S,4R)-3,4-dihydroxypyrrolidin-2-yl)thiazolidin-4-oneC13H15ClN2O3S[α]D25=-67.0 (c 1.0, MeOH)Source of chirality: d-mannose and asymmetric synthesisAbsolute configuration: (2R,3S,4R), (S)thiazolidin-4-one