Kazumi Ohta

The manners of aromatization of a new 10-membered ring 1,6-diyn-3-ene system under basic conditions

Treatment of a novel 10-membered ring 1,6-diyn-3-ene compound 1 with alcoholic KOH solution gave istohiochromanol derivatives through a polar pathway. On the other hand, treatment of 1 with DBU in CCl4 afforded 8-chloroisothiochromane derivatives through a free radical pathway.

Enantiospecific synthesis of C20C28 segment of concanamycin A: Application of diethylisopropylsilyl protecting group

A complex C20C28 segment5 of concanamycin A (1) has been first synthesized without side reactions by effective de-O-silylation of2a, which was constructed from the ethyl ketone3 by glycosidation with the fluoride4.

A novel monocyclic dienediyne system : synthesis and mode of aromatization

Abstract The novel monocyclic dienediyne 2 , which is a simplified analogue of the neocarzinostatin chromophore ( 1 ), was synthesized from D-xylitol via conversion of the keto-aldehyde 13 into the highly strained 10-membered ring compound 14 by a simple intramolecular aldol condensation as the key step. The mode of cycloaromatization of 2 by a thiol addition, reminiscent of the chemistry of 1 , was also demonstrated.

Novel designed enediynes: Molecular design, chemical synthesis, mode of cycloaromatization and guanine-specific DNA cleavage

The molecular design and chemical synthesis of novel enediyne molecules related to the neocarzinostatin chromophore (1), and their chemical and DNA cleaving properties are described. The 10-membered enediyne triols 16-18 were effectively synthesized from xylitol (10) in a short step, and found to be quite stable when handled at room temperature. The representative and acylated enediyne 16 was cycloaromatized by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in cyclohexa-1,4-diene-benzene to give the benzenoid product 21 through a radical pathway. On the other hand, the enediyne 16 was cycloaromatized by diethylamine in dimethyl sulfoxide-Tris-HCl, pH 8.5 buffer to afford another benzenoid product 22 as a diethylamine adduct through a polar pathway. Furthermore, the enediynes 16-18 were found to exhibit guanine-specific DNA cleavage under weakly basic conditions with no additive.

Design, synthesis and DNA cleaving profiles of hybrids containing the novel enediyne and naturally occurring DNA intercalates

The designed hybrids 5–11 containing the DNA cleavable enediyne 4 and naturally occurring DNA intercalators 12–18cleave DNA effectively under alkaline conditions without any additive; the hybrids 5 and 11 exhibit the strongest DNA-cleaving abilities with the identical high purine base (G>A) selectivities for their DNA-cleavage profiles.

Cycloaromatization and DNA cleavage of novel enyne-allene systems

The novel enyne-allene sulfones 5–8 were prepared by m-chloroperbenzoic acid oxidation of the corresponding enediyne sulfides 1–4; the enyne-allene sulfones 6–8 having a leaving group at the allylic position were aromatized by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)viathe allene-ene-cumulene intermediate 10 and showed DNA-cleaving activities under basic conditions without any additive.

The novel selenium mediated aromatization of a 1,6-diyn-3-ene system related to neocarzinostatin chromophore

Treatment of 1,6-diyn-3-ene system 1 with SeO2 caused a Myers type cyclization to produce a biradical 6 through an enyne–allene system 5 which was generated by an ene reaction of 1 with SeO2, in analogy with the case of neocarzinostatin chromophore.

Design, cycloaromatization and guanine-selective DNA cleavage of novel enediynes

The novel enediynes 7–9 are synthesized from xylitol 1via the keto-enediyne 2; they are aromatized by 1,8-diazabicyclo[5.4.0]undec-7-ene in cyclohexa-1,4-diene–benzene through a radical pathway and by diethylamine in Me2SO–tris-HCl, pH 8.5 buffer through a polar pathway, and exhibit gunine-selective DNA cleavage under basic conditions with no additive.

Design and synthesis of 1-thia-3,8-diyn-5-ene systems with DNA-cleaving properties related to the neocarzinostatin chromophore

1-Thia-3,8-diyn-5-ene compounds 5–10, which are derivatives of the parent compound 1 are synthesized in a short step with high stability; these compounds show DNA-cleaving activity under basic conditions in the absence of any additives.