Magoichi Sako

Formation of a novel bicyclic γ-lactam with isopenicillin N synthase

Incubation of isopenicillin N synthase (IPNS) with [(5S)-5-amino-5-carboxypentanoyl]-L- homocysteinyl-L-cysteine (14) resulted in the formation of a novel bicyclic γ-lactam (17) containing an intramolecular disulphide linkage.

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.

Reductive debromination of 5-bromouracils by 1-benzyl-1,4-dihydronicotinamide

Abstract N(1)-Unsubstituted 5-bromouracils with or without a substituent in position 6 undergo reductive debromination with ease most likely via a one-electron transfer process upon treatment with 1-benzyl-1,4-dihydronicotinamide under thermal conditions.

Facile generation of hydroxyl radical by photolyis of pyrimido[5,4-g]pteridinetetrone N-oxides in aqueous solution. A new efficient DNA-photocleaving agent

Photolyis of pyrimido[5,4-g]pteridinetetrone N-oxide 2 in water with UV–VIS light (>355 nm) provides a convenient and efficient method for the clean generation of hydroxyl radicals, which are useful as DNA-cleaving agents.

N 6 -substituent effect on the photooxidation of 2′,3′-O- isopropylideneadenosines with a pyrimido[5,4-g]pteridinetetraone N-oxide. Chemical evidence for the generation and reactivity of adenosyl cation radicals

A comparative study on the photooxidation of 2′,3′-O-isopropylideneadenosine 1a and its N6-benzoyl, N6-monomethyl, and N6,N6-dimethyl derivatives, 1b–d, with a pyrimido[5,4-g]pteridinetetraone N-oxide (PPO) was carried out. The ease of photooxidative consumption of the adenosines by the PPO is in the order of 1d > 1c > 1a > 1b, which is parallel to their oxidation-peak potentials. Although substrates 1a and 1b underwent oxidative intramolecular cyclisation to the corresponding 5′-O,8-cycloadenosines, 2a and 2b, even in low yield, substrates 1c and 1d were exclusively oxidised at the N6-methyl group to give the corresponding N6-formyl derivatives, 3 and 4, together with minor amounts of demethylated products, 1a and 1c. The present observations provide chemical evidence for the generation and reactivity of adenosyl cation radicals.

Reductive cleavage of the O−C(8) bond in 5'-O,8-cycloadenosines. Intramolecular protection of the 8-position and the 5'-hydroxy group in adenosines

Upon treatment with NaBH3CN in acetic acid at ambient temperature, N6-acyl-5′-O,8-cycloadenosines (1) with or without carbon functional groups on the 2-position undergo exclusively a reductive O–C(8) bond cleavage to give the corresponding N6-acyladenosines (2).

Photo-oxidative decarboxylation of phenylacetic acids induced by pyrimido[5,4-g]pteridine-10-oxide involving a single-electron-transfer process in both Stages

Irradiation of phenylacetic acid derivatives (3a–d) in the presence of pyrimido [5,4-g]pteridine-10-oxide (1) with UV visible light gives the corresponding benzaldehyde derivatives (4a–d) as the major product via a single-electron-transfer process in both stages.

Novel synthesis of purine acyclonucleosides possessing a chiral 9-hydroxyalkyl group by sugar modification of 9-D-ribitylpurines

A novel approach to the synthesis of purine acyclonucleosides having chiral carbons in the N9-hydroxyalkyl chain was achieved by using 9-(2,3-O-isopropylidene-D-ribityl)purines 1, which are readily prepared from commercially available purine nucleosides. 9-[(2S,3R)-2,3,4-Trihydroxybutyl]purines 4a and 4b, 9-[(2S,3S)-2,3,4-trihydroxybutyl]purines 6a and 6b, L-eritadenine 8, and its analogue 11 are conveniently synthesized via key intermediates, (2S,3S)-2,3-isopropylidenedioxy-4-(purin-9-yl)butanals 2 prepared by NaIO4 oxidation of diols 1.

Synthesis of a novel 5-deaza-5-thia analogue of tetrahydrofolic acid, N-(p-{[(2-amino-6,7-dihydro-4-oxo-3H,8H-pyrimido[5,4-b][1,4]thiazin-6-yl)methyl]amino}benzoyl)glutamic acid

N-(p-{[(2-Amino-6,7-dihydro-4-oxo-3H,8H-pyrimido[5,4-b][1,4]thiazin-6-yl)methyl]amino}benzoyl)glutamic acid 4, a deaza-this analogue of tetrahydrofolic acid, was first synthesised as a diastereoisomeric mixture by the thermal condensation of 5-bromo-6-chloroisocytosine 6 with diethyl N-{p-[(3-amino-2-mercaptopropyl)amino]benzoyl}glutamate 5bvia the aliphatic S–N-type Smiles rearrangement in ethanolic pH 7 phosphate buffer solution followed by smooth alkaline hydrolysis of the ester protecting group.