Towards the synthesis of sulfonamide-based RNA mimetics

The scalable, divergent synthesis of all four monomers required for the preparation of sulfonamide-based RNA mimetics is described. Such mimetics may combine excellent mimicry of the parent RNA with enhanced (bio)chemical robustness and convenient oligomerization. As a proof of principle, a dimer resulting from the monomers is described.

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3-Azido-3-deoxy-1,2-O-isopropylidene-β-d-riboseC8H13N3O4[α]D23=+124.4 (c 0.85, CHCl3)Source of chirality: 1,2:5,6-di-O-isopropylidene-β-d-gluco-furanoseAbsolute configuration: (1R,2R,3R,4S)

3-Azido-3,5,6-trideoxy-6-(isobutyloxysulfon)-1,2-O-isopropylidene-β-d-ribo-hexofuranoseC13H23N3O6S[α]D23=+97.1 (c 0.69, CHCl3)Source of chirality: 1,2:5,6-di-O-isopropylidene-β-d-gluco-furanoseAbsolute configuration: (1R,2R,3R,4R)

3-Azido-3,5-dideoxy-5-(isobutyloxysulfonmethyl)-N6-benzoyl-adenosineC24H28N8O7S[α]D23=+6.6 (c 2.20, CHCl3)Source of chirality: 1,2:5,6-di-O-isopropylidene-β-d-gluco-furanoseAbsolute configuration: (1R,2R,3R,4R)

3-Azido-3,5-dideoxy-5-(isobutyloxysulfonmethyl)-N2-pivaloyl-guanosineC22H32N8O8S[α]D23=+47.7 (c 0.21, CHCl3)Source of chirality: 1,2:5,6-di-O-isopropylidene-β-d-gluco-furanoseAbsolute configuration: (1R,2R,3R,4R)

3-Azido-3,5-dideoxy-5-(isobutyloxysulfonmethyl)-N4-benzoyl-cytidineC23H28N6O8S[α]D23=+42.3 (c 0.26, CHCl3)Source of chirality: 1,2:5,6-di-O-isopropylidene-β-d-gluco-furanoseAbsolute configuration: (1R,2R,3R,4R)

3-Azido-3,5-dideoxy-5-(isobutyloxysulfonmethyl)-uridineC16H23N5O8S[α]D23=+31.5 (c 1.38, CHCl3)Source of chirality: 1,2:5,6-di-O-isopropylidene-β-d-gluco-furanoseAbsolute configuration: (1R,2R,3R,4R)

3-Azido-3,5-dideoxy-5-(chlorosulfonmethyl)-uridineC12H14ClN5O7S[α]D23=+42.1 (c 0.21, CHCl3)Source of chirality: 1,2:5,6-di-O-isopropylidene-β-d-gluco-furanoseAbsolute configuration: (1R,2R,3R,4R)

3-Azido-3,5-dideoxy-5-(dimethylaminosulfonmethyl)-N4-benzoyl-cytidineC21H27N7O7S[α]D23=+38.7 (c 0.61, CHCl3)Source of chirality: 1,2:5,6-di-O-isopropylidene-β-d-gluco-furanoseAbsolute configuration: (1R,2R,3R,4R)

3-Azido-3,5-dideoxy-5-(isobutylaminosulfonmethyl)-uridineC16H24N6O7S[α]D23=+48.8 (c 0.32, CHCl3)Source of chirality: 1,2:5,6-di-O-isopropylidene-β-d-gluco-furanoseAbsolute configuration: (1R,2R,3R,4R)