Tokuo Itoh

Studies on the Chemical Synthesis of Potential Antimetabolites. 31.1 A Novel Synthesis of 1-Deazaadenosine and Its Conversion to 5′-Deoxy-5′-Isobutylthio-1-Deazaadenosine (1-Deaza-Siba) and S-(1-Deazaadenosyl)-Homocysteine (1-DEAZA-SAH)

Abstract A novel route for the preparation of 7-amino-3-(β-D-ribofuranosyl)-3H-imidazo [4,5-b] pyridine (1-deazaadenosine) has been developed. Synthesis of 5′-deoxy-5′-isobutylthio-1-deazaadenosine (1-deazaSIBA) and S-(1-deazaadenosyl)-homocysteine (1-deazaSAH) is also described.

Studies on the Chemical Synthesis of Potential Antimetabolites. 32.1 Synthesis of β-D-Pentofuranosyldeazaadenines as Candidate Inhibitors for S-Adenosylhomocysteinases and Methyltransferases

Abstract 9-β-D-Arabinofuranosyldeazaadenines [1-deaza-araA (4a) and 3-deaza-araA (4b)] were prepared from 6-chloro-β-D-ribofuranosyl-1- (6a) and -3-deazapurine (6b), respectively. Synthesis of 2′-deoxy-1-deaza-adenosine (5a) from 1-deazaadenosine (6c) is also described.

Effect of transmethylation-reaction and increased levels of cAMP on superoxide generation of guinea-pig macrophages induced with wheat germ agglutinin and phorbor myristate

Superoxide (O2 −) generation of guinea‐pig macrophages induced by wheat germ agglutinin (WGA) was suppressed to a great extent by the inhibition of transmethylation with 3′‐deazaadenosine. When macrophages were stimulated with phorbor myristate (PMA) instead of WGA, the suppression of O2 − generation of macrophages was observed to be slight despite the presence of 3′‐deazaadenosine. These results were confirmed under various conditions. Thus the WGA‐stimulated O2 − generation of macrophages is probably associated with transmethylation, but the PMA‐stimulated O2 − generation is not. WGA‐stimulated O2 − generation of macrophages was also inhibited in the presence of dibutyryl cAMP or prostaglandin E2 (PGE2), substances that increase intracellular cAMP, but PMA‐stimulated O2 − generation was only slightly affected by these compounds. These results suggest that the mechanism for O2 − generation of macrophages caused by WGA is different from that for O2 − generation caused by PMA.

Studies on the Chemical Synthesis of Potential Antimetabolites. 36. Synthesis and Some Biochemical Properties of (±)1-Deazaaristeromycin

Abstract Chemical synthesis of a carbocyclic nucleoside, (±)1-deaza-aristeromycin (1), is described. Compound 1 was found to possess only a weak inhibitory effect on calf intestine adenosine deaminase. For rabbit liver S-adenosylhomocysteinase 1 showed weak affinity but acted as a potent irreversible inactivator.

Studies on the Chemical Synthesis of Potential Antimetabolites. 35.1 Synthesis of 2-Chloro-1-deazaadenosine and 2-Chloro-1-deazainosine as Candidate Inhibitors for S-Adenosylhomocysteinases and Methyltransferases

Abstract The syntheses of 2-chloro-1-deazaadenosine (2) and 2-chloro-1-deazainosine (3) are described. Conversion of 7-ribosylated 6-chloro-1-deazapurine 3-oxide to the desired 2,6-disubstituted 9-ribosyl-1-deazapurines was effected by a series of reactions involving “deoxygenative chlorination” and transglycosylation in satisfactory yields.

Studies on the Chemical Synthesis of Potential Antimetabolites. 371. Synthesis of 3-Deazaadenine Nucleosides Modified at the Sugar Moiety

Abstract Several types of 3-deazaadenine pentofuranosides, represented by 9-(3-deoxy-β-D-glycero-pent-3-enofuranosyl)-3-deazaadenine (1), 9-(5-deoxy-β-Q-erythro-pent-4-enofuranosyl)-3-deazaadenine (2) and 9-β-D-xylo-furanosyl-3-deazaadenine (3), were prepared starting from 6-chloro-9-β-D-ribofuranosyl-3-deazaadenine (4).