Synthesis of C-glycosidically linked ADP glycero-β-d-manno-heptose analogues

C-Glycosides of l-glycero-d-manno- and d-glycero-d-manno-heptose containing either (S)- or (R)-2-hydroxypropyl aglycons are easily accessible compounds via condensation of reducing heptoses with pentane-2,4-dione. 2′,3′-Di-O-acetyl adenosine was transformed into the corresponding 5′-O-cyanoethyl N,N-diisopropylaminophosphoramidite derivative, which was coupled in fair yields to the O-acetylated diastereoisomeric C-glycosidic alcohols. Oxidation of the phosphite triesters followed by deprotection furnished four ADP-heptose analogues, wherein the heptosyl phosphate moiety had been replaced by a three carbon-skeleton. The compounds serving as substrate analogues will be used for co-crystallization experiments with ADP heptosyl transferases.

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5,6,7,9,10-Penta-O-acetyl-4,8-anhydro-2-O-[bis(benzyloxy)]phosphoryl]-1,3-dideoxy-l-lyxo-l-manno-decitolC34H43O15P[α]D20=-31 (c 0.8, CHCl3)

5,6,7,9,10-Penta-O-acetyl-4,8-anhydro-2-O-[bis(benzyloxy)]phosphoryl]-1,3-dideoxy-l-lyxo-l-gluco-decitolC34H43O15P[α]D20=-49 (c 0.7, CHCl3)

4,8-Anhydro-1,3-dideoxy-l-lyxo-l-manno-decit-2-yl phosphate (ammonium salt)C10H21O10P[α]D20=-29 (c 0.7, H2O)

4,8-Anhydro-1,3-dideoxy-l-lyxo-l-gluco-decit-2-yl phosphate (ammonium salt)C10H21O10P[α]D20=-50 (c 0.7, H2O)

Adenosine 5′-(4,8-anhydro-1,3-dideoxy-l-lyxo-l-manno-decit-2-yl)phosphate (triethylammonium salt)C20H32N5O13P[α]D20=-34 (c 0.8, H2O)

Adenosine 5′-(4,8-anhydro-1,3-dideoxy-l-lyxo-l-gluco-decit-2-yl)phosphate (triethylammonium salt)C20H32N5O13P[α]D20=-45 (c 0.8, H2O)

Adenosine 5′-(4,8-anhydro-1,3-dideoxy-d-ribo-l-manno-decit-2-yl)phosphate (triethylammonium salt)C20H32N5O13P[α]D20=-19.8 (c 0.8, H2O)

Adenosine 5′-(4,8-anhydro-1,3-dideoxy-d-ribo-l-gluco-decit-2-yl)phosphate (triethylammonium salt)C20H32N5O13P[α]D20=-31 (c 0.8, H2O)