Yoshimi Yamada

Genetic regulation of the RUNX transcription factor family has antitumor effects

Runt-related transcription factor 1 (RUNX1) is generally considered to function as a tumor suppressor in the development of leukemia, but a growing body of evidence suggests that it has pro-oncogenic properties in acute myeloid leukemia (AML). Here we have demonstrated that the antileukemic effect mediated by RUNX1 depletion is highly dependent on a functional p53-mediated cell death pathway. Increased expression of other RUNX family members, including RUNX2 and RUNX3, compensated for the antitumor effect elicited by RUNX1 silencing, and simultaneous attenuation of all RUNX family members as a cluster led to a much stronger antitumor effect relative to suppression of individual RUNX members. Switching off the RUNX cluster using alkylating agent–conjugated pyrrole-imidazole (PI) polyamides, which were designed to specifically bind to consensus RUNX-binding sequences, was highly effective against AML cells and against several poor-prognosis solid tumors in a xenograft mouse model of AML without notable adverse events. Taken together, these results identify a crucial role for the RUNX cluster in the maintenance and progression of cancer cells and suggest that modulation of the RUNX cluster using the PI polyamide gene-switch technology is a potential strategy to control malignancies.

Unsymmetrical ketone synthesis via palladium catalyzed carbonylation of organic halides

Abstract Aryl alkyl (or benzyl) ketones are selectively prepared by the reaction of aryl iodides and alkyl iodides (or benzyl chlorides) in the presence of a stoichiometric amount of zinc-copper couple and a catalytic amount of palladium(0) complex under an atmospheric pressure of carbon monoxide.

Palladium catalyzed oxidations of secondary alcohols

Abstract Palladium catalyzed oxidations of secondary alcohols making use of bromobenzene as an oxidant have been described, where 6 kinds of alcohols have been oxidized to the corresponding ketones in excellent yields.

Palladium catalyzed oxidation of Δ2, Δ3, and Δ4-unsaturated alcohols

Palladium (0.6~3 mol%) catalyses the oxidation of Δ2, Δ3, and Δ4 -unsaturated aloohols to the copresponding ketones in good yields, where bromomesitylene or bromobenzene ie used as an oxidant.

A new addition reaction of trialkyl phosphite and alkyl halide to nitrone

Abstract N-Substituted 1-(alkoxyamino)alkylphosphonates were obtained by a new addition reaction of trialkyl phosphite and alkyl halide to nitrone. A push-pull type mechanism was suggested for the addition reaction.

Palladium catalyzed thiono-thiolo allylic rearrangement of o-allyl phosphoro- and phosphonothionates

A new thiono-thiolo allylic rearrangement of phosphoro- and phosphono-thionates with Pd(PPh3)4 catalyst is described, where a variety of thionates are converted to the corresponding thiolates in excellent yields.

Palladium(ii) catalyzed thiono-thiolo rearrangement of propargyl thionophosphates

Abstract Palladium(II) effectively catalyzes the [3,3]-sigmatropic type rearrangement of propargyl thionophosphates to provide allenyl thiolophosphates specifically.

Palladium catalyzed thienylation of allylic alcohols with 3-bromothiophene

There have been reported a few devices to overcome this difficulty by making use of relatively easily available 3-bromothiophene2 as a key compound. Among them, the reaction with 3-thienyllithium3 has been widely applied to prepare 3-substituted thiophenes. However, this reagent is unstable over -70°C and does not react with the less reactive electrophiles such as alkyl iodide, but decomposes at higher temperature to give a ring-opening product. 4

Steric structure–activity relationships of the rice blasticide, S-2900 (diclocymet)†

The four diastereomers of 2-cyano-N-[1-(2,4-dichlorophenyl)ethyl]-3,3-dimethyl-butyramide were prepared by a direct HPLC separation with chiral columns. The [(S)acid, (R)amine]-isomer was the most antifungal among the diastereomers tested. Because of the lability of the clinical group in the acid moiety, the (RS)-(R)-isomer is being developed as a rice blasticide. (S-2900, proposed common name diclocymet).