Mitsuo Akiba

Organotellurium Compounds 8. Aryltellurols as Reducing Agents

Abstract Phenyltellurol and 2-thienyltellurol, generated in situ, have been found to act as selective reductants towards a number of representative organic substrates.

α-Methoxythioanisole. Further Uses as an Umpolung Reagent

Abstract The facile lithiation of thioacetals has led to their extensive development as Umpolung reagents of great utility in general organic synthesis.1 In contrast, the corresponding monothioacetals, such as α-alkoxysulfides, have received little attention for similar synthetic purposes. The most investigated reagent of this class has been the α-lithio derivative (2) of α-methoxy-thioanisole (methoxymethylphenylthioether, 1), which we will henceforth refer to as LMT. The first reported use of LMT was in 1975 by Trost, who showed that it added cleanly to the carbonyl of several bicyclic lactones.2 Subsequent studies of LMT have been limited to one example of its addition to a lithiated tosylhydrazone to give eventually an enol ether,3 and several cases of its addition to ketone carbonyls as the first step of an unsaturated aldehyde synthesis.4,5 We now report a new, convenient and non-hazardous synthesis of α-methoxythioanisole (1), as well as a broad overview of the reactions of its lithio derivative LM...

Organogermanium compound, Ge-132, forms complexes with adrenaline, ATP and other physiological cis-diol compounds

BACKGROUND In mammals, adrenaline and ATP are life-essential vicinal diol and cis-diol functional groups. Here, we show that interactions between a safe organogermanium compound and these cis-diol compounds have the potential to regulate physiological functions. In addition, we represent a possible new druggable target for controlling the action of cis-diol compounds. RESULTS We analyzed a single crystal structure of organogermanium 3-(trihydroxygermyl)propanoic acid (THGPA), a hydrolysate of safe Ge-132, in complex with catecholamine (adrenaline and noradrenaline), and evaluated the affinity between several cis-diol compounds and THGPA by NMR. An in vitro study using normal human epidermal keratinocytes was performed to investigate the inhibition of cis-diol compound-stimulated receptors by THGPA. At high concentration, THGPA inhibited the calcium influx caused by adrenaline and ATP. CONCLUSION This study demonstrates that THGPA can modify cis-diol-mediated cell-to-cell signaling.

Synthesis and properties of germa-γ-lactones

Abstract Trialkylgermylpropanoic acids treated with 1 mole of bromine afford the monobromopropanoic acids, which are converted into the corresponding germa-γ-lactones in good yields by hydrolysis. The physical, chemical, and biological properties of these compounds are described.

INHIBITORY EFFECT OF ORGANOGERMANIUM COMPOUNDS ON THE BIOLOGICAL MAILLARD REACTION

Glucose and amino-group of proteins form Schiff bases, whose reaction is reversible, and then Amadori products can be formed by rearrangement from the Schiff bases by the biological Maillard reaction. Many different types of advanced glycation end products (AGE) can be formed from Amadori products. Among AGE, formation of pentosidine must be more important biological and physiological marker of the Maillard reaction. Inhibitory effect of Ge-132 was observed on the formation of pentosidine by the reaction of arginine, ribose and lysine as well as the further progress reaction of Amadori product, fructose lysine, to pentosidine in the presence of arginine. These results indicated that organogermanium compounds, in particular Ge-132, inhibited both of formation of Amadori rearrangement adducts and further progress reaction to AGE, however, Ge132 was found to have no free radical scavenging activity. By the detailed 1H-NMR analyses of the reaction of Ge-132 with glucose or chemically synthesized glucofuranose derivatives, it was found that Ge-132 made an complex with glucofuranose form of glucose and inhibited the early stage of the Maillard reaction. Ge-132 was also found to make a complex with Amadori rearrangement adducts such as fructoselysine to stabilize and inhibit the futher progress of the Maillard reaction. INTRODUCTION Much attention has been focused on organogermanium compounds because of their physiological and biological activities. Synthesis of trialkylgermanium acetate was reported in 1962 by Kaars et al as the first biological active organogermanium compound, which demonstrated to have an antifungal activity). In 1968, Asai and Kakimoto reported the synthesis of organogermanium sesquioxide (Ge-132)). Many in vitro and in vivo experiments revealed that Ge-132 is a unique biological and physiological active compound of extremely low toxicity such as biological responce modifying (BRM) activity, antiviral activity, and regulation of calcium metabolism, alleviation of carcerous pain and osteoscope). In 1912, Maillard found that glucose or other reducing sugars react with amino acids to form adducts that undergo a series of non-enzymatic browning reaction in the storedor heattreated foods). In recent years many reports have suggested that the Maillard reaction plays an important role of diseases associated with diabetes and aging. Maillard products have been observed in vivo in association with several long-lived proteins such as lens crystallines and collagen. The aldehyde group of glucose reacts with the amino groups of proteins to form Schiff base adducts, followed by Amadori rearrangement, and a series of dehydrations and rearrangements to form advanced glycation end products (AGE)). Recently, Nakamura et al. reported that organogermanium compounds (2carboxyethylgermanium sesquioxide: Ge-132, and 2-Carboxy-2-aminoethylgermanium sesquioxide: Ge-385) were effective in suppressing the formation of AGE, which is suspected to contribute to the development of diabetic complication, from serum proteins, collagen and lens crystalline although the detailed mechanism is not clear 6), These backgrounds prompted us to investigate the chemical aspect of the mode of action of organogermanium compounds using the biomimic Maillard reaction and NMR technique. In this paper, inhibitory mechanism of Ge-132 and its related compounds on the Maillard reaction will be presented.

Organogermanium compounds: First synthesis of bioactive trithiagermatranes substituted with novel functional groups

Abstract The synthesis and properties of trithiagermatranes ( 3 ) via reaction of tris(2-mercaptoethyl)amine with trimethoxygermyl adducts ( 5 ) and germanium sesquioxides ( 6 ) are described.

Organogermanium compounds; spectroscopic study on the influence of aryl groups in the organogermanium aryl compounds on the (P-d)π interaction

The synthesis and properties of arylgermanium compounds through the reactions of aryllithium with germanium halides were investigated. 1 H-Nmr spectroscopic analysis showed the (p-d) π interaction between the germanium atom and the double bond of the aryl group to diminish in the following group order: 2-benzofuranyl>2-furanyl>2-benzothiophenyl>2-thiophenyl>phenyl group

Reaction of Benzoquinones with Cyclic Amines; 1H- and 13C-Nmr Spectra of Amine-adducts

Reaction of unsymmetrical 1,4-benzoquinone with cyclic amines afforded a mixture of amine-adducts. Using dibromoquinone as the substrate, monoamine adduct was obtained regioselectively. Regiochemistry was determined by 1 H- and 13 C-nmr spectroscopic analyses

A convenient synthesis of 7-methoxymitosene by the photolysis of aminobenzoquinones

A simple method for the preparation of pyrrolo[1,2-a]indoloquinone derivatives using the photolysis of amino-quinones has led to a formal synthesis of 7-methoxymitosene.