Katsumaro Minamoto

As-triazine chemistry—VI : Mass spectra of as-triazines and their N-oxides

Abstract The mass spectra of some substituted as -traizines and their N-oxides were measured, in order to investigate the intensity relationship between (M - 16) and (M - 17) ion peaks as functions of substituents and the positions of N-oxide groups in these compounds. These ion species proved useful for detecting an N-oxide group and predicting its orientation when the as -triazine ring is suitably substituted. The marked spectral correlation between these compounds permits certain crude generalizations of the cleavage processes. The observations implying electron impact induced 1,4-migrations of ether- and anilino-phenyl groups are also described.

Synthesis of 1-(3′-deoxy-β-D-glycero-pentofuran-2′-ulosyl)uracil by selective elimination reactions

Abstract For the synthesis of y 1-(3′-deoxy-β-D-glycero-pentofuran-2′-ulosyl)uracil (16), the precursor, 5′-O-benzoyl derivative (2),2 was elaborated in a variety of ways. 1-(5′-O-Benzoyl-3′-O-tosyl-β-D- lyxofuranosyl)uracil (4)2 was benzoylated to N3-benzoyl-1-(2′,5′-di-O-benzoyl-3′-O-tosyl-β-D- lyxofuranosyl)uracil (5), which directly yielded 2 on treatment with sodium benzoate. 1-(3′,5′-Di-O- benzoyl-2′-O-tosyl-β-D-lyxofuranosyl)uracil (8) and its 3′,5′-O-isopropylidene analog (10) resisted elimination reactions, thus proving absolute selectivity in the elimination of the derivatives of 1-β-D- lyxofuranosyl-uracil. Seeking a more economical path to 2, 1-(5′-O-benzoyl-β-D-lyxofuranosyl)uracil (11) was first benzoylated to give 2′,5′-di-O-benzoate (12), accompanied by 3′,5′-di- and 2′,3′,5′-tri-O- benzoate. Mesylation of the major product (12) gave 1-(2′,5′-di-O-benzoyl-3′-O-mesyl-β-D- lyxofuranosyl)uracil (15), which, on treatment with sodium benzoate, gave 2 in an highly improved yield. Basic hydrolysis on 2 gave compound 16.

Stereoselective Reactions OF 1-(4,6-O-Benzylidene-2,3-Didehydro-2,3-dideoxy-3-nitro-β-D-hexopyranosyl)uracil with some Nucleophiles¶

Abstract Michael addition of benzylamine, piperidine, morpholine, pyrrolidine, cyclohexylamine, allylamine and dimethylmalonate to the nitroolefin (5) generated in situ from 1-(4,6-O-benzylidene-3-deoxy-3-nitro-β-D-glucopyranosyl)uracil (4b) gave the corresponding 2-(substituted-amino)-3-deoxy-3-nitro-β-D-glucopyranosides (6a-f and 6h). Reaction of 4b with N,N-carbonyldiimidazole directly gave 6g. Compound 4b was converted into the 2-deoxy analogue (8), which was reduced to the 3-amino (9) and 3-hydroxylamino analogue (10). ¶ This paper is dedicated to Dr. Yoshihisa Mizuno, emeritus professor of Hokkaido University, to celebrate his 75th birthday.

Synthesis of 2,2'-anhydro-1-(3'-deoxy-3'-iodo-β-D-arabino-furanosyl)thymine and its derivatives as versatile synthetic intermediates

Abstract 2,2′ -Anhydro-1- (3′ -deoxy-3′ -iodo-5′ -O-trityl-B-D-arabinofuranosyl)-thymine (2) was synthesized from 2′,3′ -didehydro-3′-deoxythymidine (DHT) (1). Compound 2 was readily converted into 2′,3′-anhydro-lyxofuranosyl derivatives 4-6. Reaction of 4a with some nucleophiles (N3 -, OMe-, Cl-) gave the corresponding 3′-substituted arabinonucleosides (7b,d,f) together with the minor xylosyl isomers (8a,c). Compounds 7b,d,f and 8a were deprotected to 7c,e,g and 8b, respectively.

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 the derivatives of 5,6-diaryl-2,5-dihydro-1,2,4-triazines with dimethyl acetylenedicarboxylate—structural reassignments of the products and further observations

Abstract The structures of the dihydro derivatives of 5,6-diaryl-1,2,4-triazines and of the products from the title reactions have been reassigned as 5,6-diaryl-2,5-dihydro-1,2,4-triazines ( 5 a-g) and 2,6-diaryl-4-methyl-5-substituted-1,8-bis-methoxycarbonyl-3,4,7-triaza-bicyclo[3.3.0]octa-2,7-dienes ( 7 a-g), respectively.

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.

Synthesis of some piperidine sugar uracil nucleosides with a 2,3′-substituted-imino bridge

Base-catalysed isomerization of 2,3′-(substituted-imino)-1 -(3′-deoxy-β-D-lyxofuranosyl)uracils (1) to the corresponding pyranosyl analogues (2) was extended to the synthesis of analogous 2,3′-imino nucleosides having a piperidine sugar moiety. Trimesyluridine (3) with methylamine gave the 2,3′-methylimino-5′-O-mesyl-lyxofuranosyluracil (5). Compound (5) with ammonia, methylamine, orbenzylamine gave the corresponding5′-amino(6a),5′-methylamino(6b), or 5′-benzylaminoanalogue (6c), while the 3′,5′-di-O-mesyl derivative (4) of 2,2′-anhydrouridine with aniline gave the 2,3′-phenylimino analogues (6d), (7), and (8). Alkaline hydrolysis of compounds (6b and c) with 3M-NaOH-EtOH gave the corresponding piperidine sugar nucleosides (9a and b), while similar treatment of compound (6d) gave the piperidine (9c) and the dianilinolyxofuranosyluracil (10). On the other hand, the same reaction with compound (6a) yielded 3-hydroxypyridine (12) and N2-methylisocytosine (13)via thefuranosyl-to-piperidinyl isomerization, anomericbond fission, and elimination of compound (13) by [1,2]-hydride shift. 2′-O-Methyl analogue of (6a), compound (18b), with alkali gave N2-methyl-N2-(4-pyridino)isocytosine (19) exclusively, confirming the above mechanism for the formation of compounds (12) and (13) from (6a).

SYNTHESIS AND REACTIONS OF SOME 3', 4'-UNSATURATED 2', 3'-SECOURIDINE ANALOGUES

Abstract 2′,3′-Dibromo-2′,3′-dideoxy-5′-O-trityl-2′,3′-secouridine (8) with sdKF gave the 3′,4′-didehydro-2,2′-anhydro nucleoside 9, which was deprotected to 10. Hydrolysis of 9 gave 3′,4′-didehydro-3′-deoxy-5′-O-trityl-2′,3′-secouridine (11a). Similarly, compound 9 with pyridinium halides gave the corresponding 2′-deoxy-2′-halo nucleosides (11b-d). Compound 11d with azide ion gave 2′-azido analogue 11e. Compound 9 with an excess amount of azide ion gave the 2′-azido triazole (13).

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.