Kosaku Hirota

Novel Synthesis of Pyrido[3,4-d]pyrimidines, Pyrido[2,3-d]pyrimidines, and Quinazolines via Palladium-catalyzed Oxidative Coupling

Oxidative-coupling of 6-azavinyl(or vinyl)-1,3-dimethyluracil derivatives (1, 5, and 7) with electron-deficient olefins in the presence of palladium acetate led to the formation of the corresponding 6-substituted pyrido[3,4-d]pyrimidines (4), pyrido[2,3-d]pyrimidines (6), and quinazolines (8 and 9), respectively, via an intermediacy of azatriene

A remarkable solvent effect toward the Pd/C-catalyzed cleavage of silyl ethersElectronic supplementary information (ESI) available: characterization data and references and supplementary Tables 4 and 5. See http://www.rsc.org/suppdata/cc/b2/b211313a/

Selective hydrogenation conditions of olefin, benzyl ether and acetylene functionalities in the presence of TBDMS or TES ether have been developed.

Novel and efficient synthesis of 8-oxoadenine derivatives

A novel synthetic method of 8-oxoadenine derivatives (3 and 4) is reported. This widely applicable synthetic method was realized through the use of 5-amino-4-cyano-2-oxoimidazole derivatives (2) as the key intermediates. A variety of substituents were successfully introduced to the 2- and 9-position of the 8-oxoadenine nucleus.

Pd/C(en)-catalyzed regioselective hydrogenolysis of terminal epoxides to secondary alcohols

Various terminal epoxides, such as 1,2-epoxyalkanes, glycidyl ethers and glycidol, were hydrogenolyzed to give secondary alcohols with high regioselectivity using a 10% Pd/C–ethylenediamine complex as a catalyst under entirely neutral conditions.

Nucleosides. Part 6. New chemical modification of the ribosyl moiety in uridines; synthesis of 2,2′-anhydro-1-[5-deoxy-5-(substituted thio)-β-D-arabinofuranosyl]uracil derivatives and their conversion into 3′,5′-epithiopyrimidine nucleosides

Treatment of 5-substituted 2′,5′-dichloro-2′,5′-dideoxyuridines (1) with thiols such as thiophenol, thioacetic S-acid, thiobenzoic S-acid, toluene-α-thiol, and ethanethiol in the presence of triethylamine or 1,1,3,3-tetramethylguanidine in N,N-dimethylformamide (DMF) gave the corresponding 2,2′-anhydro-1-[5-deoxy-5-(substituted thio)-β-D-arabinofuranosyl]uracils (2a–f) in good yield. Treatment of 5-substituted 2,2′-anhydro-1-(5-acetylthio-5-deoxy-β-D-arabinofuranosyl)uracils (2b) and (2f), prepared with ease by the reaction of (1) with thioacetic S-acid, with methanolic sodium methoxide gave the corresponding 1-(3,5-dideoxy-3,5-epithio-β-D-xylofuranosyl)uracils (9a) and (9c) fused with a thietane ring in the sugar moiety. None of the newly synthesized nucleosides displayed appreciable cytotoxicity or antiviral activity in primary rabbit cell cultures.

IODOBENZENE DIACETATE-PROMOTED N-N AND N-O BOND FORMATION FOR PYRAZOLO-AND ISOXAZOLOPYRIMIDINE SYNTHESES

Pyrazolo[3,4-d]pyrimidine-4,6-dione derivatives were efficiently synthesized via the intramolecular N-N bond coupling of 5-iminomethyl-6-aminouracil derivatives using iodobenzene diacetate. The oxidative coupling was also applied to the analogous N-O bond formation producing isoxazolo[3,4-d]primidine-4,6-dione derivatives.

Easy and partial hydrogenation of aromatic carbonyls to benzyl alcohols using Pd/C(en)-catalyst

Although 10% Pd/C catalyzed hydrogenolysis of aromatic ketones and aldehydes readily affords methylene compounds via intermediary benzyl alcohols, the employment of 10% Pd/C–ethylenediamine complex [Pd/C(en)] as a catalyst eased the formation of benzyl alcohols.

A Convenient Synthesis of Acyclic Adenosines with an Unsaturated Side Chain by Modification of 9-(2,3-O-Isopropylidene-D-Ribityl)Adenine

Abstract In expectation of discovering their antiviral activity, acyclic adenosine derivatives 7, 11, 12, and 16 were designed as analogs of neplanocin A (NPA) and L-eritadenine which are strong inhibitors of S-adenosyl-L-homocysteine hydrolase. The 1′,5′-seco-analog of 4′-deoxymethyl-NPA (DHCA) 7 was synthesized by dideoxygenation of 9-(2,3-O-isopropylidene-D-ribityl)adenine (2). Acyclic DHCA analogs 11 and 16 were obtained by Wittig reaction of the aldehyde 3 with Ph3P=CHCO2Et and Ph3P=CHCN, respectively. Hydrolysis of the ester 11 afforded a vinylog of L-eritadenine 12. The synthesized acyclic nucleosides 7, 10, and 11 were evaluated for antiviral activity, however, none of them showed any significant antiviral activity.

Nucleosides. Part 5. Isolation and characterization of the stable cyclic adducts, (5R,6S)- and (5S,6S)-bromo-O6,5′-cyclo-5,6-dihydrouridines in the bromination of 2′,3′-O-isopropylideneuridine with N-bromosuccinimide

Bromination of 2′,3′-O-isopropylideneuridine (1) with N-bromosuccinimide in chloroform containing acetic acid gave two diastereoisomeric cyclic adducts, (5R,6S)- and (5S,6S)-bromo-O6,5′-cyclo-5,6-dihydro-2′,3′-O-isopropylideneuridines (4a) and (4b), whose structures were determined on the basis of their chemical reactivities and 1H n.m.r. spectral results. The cyclic adducts (4a) and (4b) formed an equilibrium mixture under acidic conditions [(4a)/(4b)= 9:11], while under neutral and basic conditions both adducts were converted into 5-bromo-2′,3′-O-isopropylideneuridine (2).

A simple and efficient synthesis of the γ-lactam analogue of β-lactam antibiotics. Ring-expansion of penicillins to homopenicillins

Irradiation of the β-ketosulphoxonium ylide (2), prepared easily from the benzylpenicillin methyl ester (1), with u.v. light results in the smooth formation of the corresponding homopenicillin methyl ester (3) which is hydrolysed to give benzylhomopenicillin (4) quantitatively.