Bogdan Doboszewski

D-Arbinose-Based Synthesis of homo-C-d4T and homo-C-thymidine

2,3,5-Tri-O-benzyl-D-arabinofuranosyl halides (chloride, bromide) were reacted with AllMgBr, MeMgBr, and VinMgBr to furnish anomeric mixtures of the C-glycosyl products. The factors that influenced the β/α ratio are discussed. The α,β-C-vinyl derivative was transformed into 1-deoxy-1-C-hydroxymethyl-β- and -α-D-arabinofuranoses (2,5-anhydro-D-glucitol and -mannitol, respectively), separable after isopropylidenation step. 2,5-Anhydro-1,3-O-isopropylidene-D-glucitol was converted into 2,5-anhydro-6-O-triphenylmethyl-D-erythro-hex-3,4-enitol and 2,5-anhydro-4,6-di-O-benzoyl-3-deoxy-D-ribo-hexitol, which were coupled with N-3-benzoylthymine under the Mitsunobu conditions to furnish two analogs of nucleosides with a -CH2- insert between sugar moieties and thymine.

PROTECTING GROUPS TRANSFER: UNUSUAL METHOD OF REMOVAL OF TR AND TBDMS GROUPS BY TRANSETHERIFICATION

The triphenylmethyl (Tr) group undergoes a transfer (transetherification or disproportionation) between the molecules of 5′-O-Tr-2′-deoxynucleosides in a process mediated by anhydrous sulfates of Cu+2, Fe+2, or Ni+2 to yield mixtures of 3′,5′-bis-O-Tr and 3′-O-Tr products. If phenylmethanol is present in a reaction medium, detritylation results with concomitant formation of phenylmethyl triphenylmethyl ether. The behavior of t-butyldimethylsilyl (TBDMS) group in 5′-O-TBDMS-2′-deoxynucleosides is exactly the same. Such type of transetherifications was not observed before for the O-Tr and O-TBDMS groups.

Easy Access to 2,5-Anhydro-1,3-O-isopropylidene-D-glucitol

Acid-catalyzed cyclization of D-mannitol followed by isopropylidenation furnished 2,5-anhydro-1,3-O-isopropylidene-D-glucitol, conveniently isolated by dry column vacuum chromatography.

Deoxygenation at the C3 position of d- and l-arabinofuranose: stereospecific access to enantiomeric cordycepose derivatives

Efficient synthesis of 3-deoxy-1,2-O-isopropylidene-β-D- and β-L-threo-pentofuranose (1,2-O-isopropylidene-β-D- and β-L-cordycepose) was accomplished starting from D- and L-arabinofuranose derivatives, respectively, by the action of LiBH(Et)3 on corresponding intermediate 3-O-lyxofuranosyl trifluoromethanesulfonates.

3-De­oxy-1,2-di-O-isopropyl­idene-5-O-tosyl-d-threo-pentofuran­ose

In the crystal structure of the title compound, C15H20O6S, the two independent molecules crystalllize in a chiral setting with two different conformations, twisted 4 T 3 and envelope 4 E, for the furanose rings. Weak C—H⋯O contacts strengthen the crystal structure.

Crystal structure of (S)-1-O-tert-butyl­diphenyl­silylglycerol: eight chiral mol­ecules in a triclinic cell

In the triclinic crystal form, the molecules are linked by hydrogen bonds into an infinite assembly propagating along the a axis; hydrophobic tert-butyl and phenyl groups form an external coating of the assembly.

Dehydration of D-mannitol: building block for C-nucleoside synthesis

D-Mannitol 1 is a convenient starting material for organic synthesis because of the homotopic relation between the upper and the lower part of the molecule. For this reason dehydration of 1 via 2-5 hydroxyl groups yields one product only, i.e. 2,5,anhydro-D-glucitol 2. Our interest in 2 and its derivative 5 stems from a possibility of application of the latter for C-nucleoside synthesis. Acid catalyzed dehydration of 1 was performed followed by some manipulations, and permitted isolation of the 2,5anhydro-4,6-di-O-benzyl-D-glucitol 5, together with 2,6-anhydro-1,3-di-O-benzyl-D-mannitol 7 (or 1,5anhydro-4,6-di-O-benzyl-D-mannitol due to a symmetry of 1). A structure of 7 was confirmed by xray analysis.

3′-O-Acetyl-2′-de­oxy­uridine

In the two independent but very similar molecules of the title compound, C11H14N2O6, both nucleobase fragments are nearly planar (both within 0.01 Å) while the furanose rings exhibit 2 E-endo envelope conformations. In the crystal, the two 3′-O-acetyl-2′-deoxyuridine molecules form a pseudosymmetric dimer of two bases connected via two nearly identical resonance-assisted N—H⋯O hydrogen bonds. The resulting pair is further connected with neighboring pairs via two similar O—H⋯O bonds involving the only hydroxyl group of the 2′-deoxyfuranose fragment and the remaining carbonyl oxygen of the nucleobase. These interactions result in the formation of an infinite ‘double band’ along the b axis that can be considered as a self-assembled analogue of a polynucleotide molecule with non-canonical Watson–Crick base pairs. The infinite chains of 3′-O-acetyl-2′-deoxyuridine pairs are additionally held together by C—H⋯O interactions involving C atoms of the uracyl base and O atoms of carbonyl groups. Only weak C—H⋯O contacts exist between neighboring chains.

2,6-Anhydro-1,3-di-O-benzyl-d-mannitol

In the title compound, C20H24O5, the six-membered pyranose ring adopts a chair conformation. The dihedral angle between the planes of the phenyl groups of the benzyl substituents is 63.1°. Two types of intermolecular O—H⋯O hydrogen bonds lead to the formation of infinite chains along the b axis. Only weak C—H⋯O contacts exist between neighboring chains.

Dimethyl hydrazine-1,2-dicarboxyl-ate-triphenyl-phosphine oxide (1/1).

In the crystal structure of the title compound, C4H8N2O4·C18H15OP, two triphenylphosphine oxide molecules and two dimethyl hydrazine-1,2-dicarboxylate molecules are connected via N—H⋯O hydrogen bonds of moderate strength and are related via a twofold rotational axis. Weak Car—H⋯ O contacts strengthen the crystal structure.