Collect. Czech. Chem. Commun. 1993, 58, 2180-2196

[5-(Adenin-9-yl)-5-deoxy-L-pentofuranosyl]phosphonates - A Novel Type of Nucleotide Analogs Related to HPMPA. II. Synthesis of L-ribo and L-xylo Configurated Derivatives by Recyclization of Diethyl (5-RS)-[1,2-O-Isopropylidene-5-O-methanesulfonyl-D-pentofuranos-5-C-yl]phosphonates under Acidic Conditions

Miroslav Otmar, Ivan Rosenberg, Milena Masojídková and Antonín Holý

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic


Further cyclic analogs of the antiviral (S)-9-(3-hydroxy-2-phosphonomethoxypropyl)adenine (I) were prepared: both anomers of [5-(adenin-9-yl)-5-doxy-L-ribofuranosyl]phosphonic acid (α-IId and β-IId) and [5-(adenin-9-yl)-5-doxy-α-L-ribofuranosyl]phosphonic acid (IIe). Recyclization reaction of diethyl (5RS-(3-O-benzyl-1,2-O-isopropylidene-5-O-methanesulfonyl-D-ribofuranos-5-C-yl)phosphonate (IVb) and diethyl (5RS-(3-O-benzyl-1,2-O-isopropylidene-5-O-methanesulfonyl-D-xylofuranos-5-C-yl)phosphonate (IVd) in trifluoroacetic acid led to cyclic aldehydes Va and Vb which were reduced to diethyl α- and β-L-ribofuranosylphosphonates VIb and α-L-xylofuranosylphosphonate VIIb. Conversion to the protected 5-O-tosylates VId and VIId, followed by reaction with adenine and deprotection, afforded the mentioned nucleotide analogs IId and IIe. An attempt to prepare L-pentofuranosylphosphonates Vc and XIII, suitable for the synthesis of nucleotide analogs of 3-deoxy-L-erythro and L-xylo configuration (IIf and IIg, respectively) by the recyclization reaction of the corresponding 5-O-methanesulfonyl derivatives IVf and XIIb failed. In this case, anhydro derivatives IXa, XVa and XVIa were isolated and identified.