Kuniki Kato

Sugar-Modified Nucleosides in Past 10 Years, A Review

In the search for effective, selective, and nontoxic antiviral and antitumour agents, a variety of strategies have been devised to design nucleoside analogs. These strategies have involved several formal modifications of the naturally occurring nucleosides, especially, alteration of the carbohydrate moiety. Since the naturally occurring purine nucleoside analog oxetanocin A and its derivatives have been found to be effective as anti-HIV-1 and anti-herpes virus agents in 1986, the syntheses of different types of sugar-modified nucleoside analogs have been reported. In this review we will give an overview of the sugar-modified nucleosides synthesized since the late 1990 according to their structural types along with the synthetic routes of some selected nucleosides.

A total synthesis of oxetanocin, a novel nucleoside with an oxetane ring

Abstract Oxetanocin has been synthesized starting from cis-2-buten-1,4-diol through α- or β-D-oxetanosyl acetate as an important intermediate which has an α-(methyl oxalyloxy)methyl group at C 2 -position.

Studies on the total synthesis of oxetanocin; II. Total synthesis if oxetanocin☆

Abstract The first total synthesis of a novel nucleoside oxetanocin 1 is described.

Design, synthesis, and biological evaluation of novel estradiol-bisphosphonate conjugates as bone-specific estrogens.

Bone deficiency causes osteoporosis and often decreases quality of life in patients with rheumatoid arthritis. Estrogens are known to protect elderly women from bone loss. Synthesis of new estradiol-bisphosphonate conjugates (E(2)-BPs) was accomplished and their in vivo activity as bone-specific estrogens were examined. Among them, MCC-565 showed selective estrogenic activity in bones; but it showed little estrogenic activity in the uterus. We also found that the linker moiety in E(2)-BPs was essential for the absorption and specificity of the conjugates.

Studies on the total synthesis of oxetanocin; I. The first synthesis of a nucleoside having oxetanosyl-N-glycoside

Abstract The first synthesis of 9-(2-oxetanyl)adenine 12 , a key intermediate for the synthesis of a novel nucleoside oxetanocin 1 , has been achieved via cyclization between allyloxycarbanion and epoxy group.

Synthetic studies on oxetanocin, a novel nucleoside with an oxetane ring synthesis of some chiral D-oxetanosyl acylates

Abstract Some chiral D-oxetanosyl acylates, promising synthetic precursors of oxetanocin, have been synthesized from D-glucose as well as from cis-2-buten-1,4-diol, wherein the most important step requires Baeyer-Villiger oxidation of the carbonyl group attached to C1-position of the corresponding oxetanes.

Synthetic studies on oxetanocin analogs: synthesis of oxetanosyl C-nucleoside, 2-deoxy-2-hydroxymethyl-β-D-erythrooxetanosyl maleimide

Abstract Synthesis of oxetanosyl C-nucleoside similar to showdomycin, 2-deoxy-2-hydroxy-methyl-β-D-erythrooxetanosyl maleimide has successfully been carried out starting from the potent intermediate of oxetanocin synthesis.

Synthesis of cleonine, amino(1-hydroxycyclopropyl)acetic acid, a novel amino acid contained in cleomycin

Abstract The synthesis of cleonine, amino(1-hydroxycyclopropyl)acetic acid, a novel amino acid contained in cleomycin, a new bleomycin-phleomycin group antibiotic, is described.

Synthesis and Structure–Activity Relationship of Dehydroxymethylepoxyquinomicin Analogues as Inhibitors of NF-κB Functions

Abstract We previously found dehydroxymethylepoxyquinomicin (DHMEQ) inhibited NF-κB activation and showed anti-inflammatory activity in vivo. Here we designed and synthesized analogues of DHMEQ and tested their biological activity as NF-κB inhibitors in human T cell leukemia Jurkat cells. The hydroxyl group at the 2-position of the benzamide moiety was found to be essential for the inhibitory activity. But etherification of this group did not diminish the activity completely. Thus, for further mechanistic studies the hydroxyl group at the 2-position may be useful for extension with a linker and biotin moiety.

Syntheses of 2,2-bishydroxymethylcyclopropyl adenine and uracil, novel carbocyclic nucleosides

Abstract Novel carbocyclic nucleoside, 2,2-bishydroxymethylcyclopropyl adenine and uracil successfully synthesized.