Kazufumi Yanagihara

First systematic chiral syntheses of two pairs of enantiomers with 3,5-dihydroxyheptenoic acid chain, associated with a potent synthetic statin NK-104

First systematic chiral syntheses of two pairs of enantiomers with 3,5-dihydroxyheptenoic acid chain, associated with a potent synthetic statin NK-104 are reported. A pair of syn diol isomers (NK-104 and its enantiomer) was obtained efficiently by diastereomeric resolution. The synthesis of a pair of anti diol isomers (3-epimer and 5-epimer) was accomplished effectively by the asymmetric aldol reaction followed by anti stereoselective reduction as key steps. Their purity determinations were effected by chiral HPLC analysis.

Stereoselective Synthesis of Some 3-Nitroglucopyranosyladenine Analogues via a Nitroolefin: Intermediate as Potential Therapeutic Agents

Abstract Three isomers of 9-(4,6-O-benzylidene-3-deoxy-β-D-hexopyranosyl) adenines (2–4) were isolated. The manno isomer 2 could be isomerized to the gluco isomer 3. The manno (2) and galacto isomer (4) were deprotected to 5 and 7, respectively. Michael addition of some organic amines and thiolates to the nitroolefin intermediate (8) gave the corresponding 2-(substituted)-3-nitro-glucopyranosides (9a-h). Compounds 9a,c,h were deprotected to 10a,c,h. Sodium azide with 8 gave the triazolo nucleoside 11, which was deprotected to 12. 2-Deoxy-3-nitro analogue 14 was also obtained. This paper is dedicated to the memory of the late Professor Tsujiaki Hata.

Reactions of Some 2,3-Anhydro Pyrimidine Nucleosides with Dilithium Tetrahalocuprates

Abstract The reaction of 1-(2,3-anhydro-5-0-trityl-β-D-lyxofuranosyl)-2-0-methyluracil (2a) and its thymine analogue (2b) with dilithium tetrahalocuprates (Li2CuX4) revealed an excellent to perfect regioselectivity, yielding 2,2′-anhydro-3′-halonucleosides (3a-d), while the same reactions with 2,3-anhdro uracil and thymine nucleosides (5a,b) gave arabinosyl (6a-d) and xylosyl halohydrins (7a-d) with respective product ratios of 7:3 to 8:2 which were estimated after mesylation to 8a-d and 9a-d.

Highly efficient synthesis of 2,2′-anhydro-1-(3′-bromo-3′-deoxy-5′-O-trityl-β-D-arabinofuranosyl)thymine and its derivatives from an unsaturated thymine nucleoside

Reaction of 5′-O-trityl-2′,3′-thymidinene 1 with hypobromous acid gave (5R,6R)-2,2′-anhydro-5-bromo-1-(3′-bromo-3′-deoxy-5′-O-trityl-β-D-arabinofuranosyl)-6-hydroxy-5, 6-dihydrothymine 3a and its (5S,6S)-trans isomer 4a. Similarly, 6-methoxy analogues (3b and 4b) and 6-acetoxy analogues (3c and 4c) of 3a and 4a were synthesized. Compounds 3a and 4a were converted into the corresponding 5,6-epoxy derivatives, 5 and 6. Deoxygenation of oxiranes 5 and 6 with Ph3P gave 2,2′-anhydro-1-(3′-bromo-3′-deoxy-5′-O-trityl-β-D-arabinofuranosyl)thymine 7, which was also obtainable in excellent yields from compounds 3a, b or/and 4a, b by treatment with Ph3PNaHCO3, or directly from unsaturated furanose 1 by one-pot synthesis via methyl ethers 3b and 4b or acetates 3c and 4c. Compound 7 was deprotected to give the mother compound 8 and was also converted into the 2, 3-lyxo epoxy thymine furanosides, 11 and 12, in high yields.