Over the last few years, we have embarked on the development of the synthesis of allyl cyanate and its rearrangement. This reaction offers an efficient transformation of the allyl alcohols into the allyl amines with high stereospecific manner even when the allyl alcohols are highly substituted at the γ-positions. Applications of this rearrangement in the context of the natural product synthesis have realized a new approach to the synthesis of amino-sugars, a new protocol for stereocontrolled allyl amine synthesis, and the first total synthesis of the peptidyl nucleoside antibiotic, blasticidin S.
We have developed a system for the comprehensive bioconversion of a series of organic chemicals through the living cells of recombinant microbes (living cells-based combinatorial chemistry; CellCombiChem). This attempt started with recombinant Escherichia coli expressing bacterial genes involved in biphenyl degradation (metabolism). The biphenyl degradation is carried out through four enzymes : biphenyl dioxygenase (BphA), dihydrodiol dehydrogenase (BphB), 2, 3-dihydrodiol dioxygenase (BphC), and hydrolase (BphD). We succeeded in synthesizing various oxidized compounds from a series of aromatic compounds, e.g. phenyl heterocycles and flavonoids, by using E. coli expressing these enzyme genes systematically (bphA, synthesis of 1, 2-cis-dihydrodiol; bphA+bphB, 1, 2-diol; bphA+bphB+bphC, picolinic acid; bphA+bphB+bphC+bphD, carboxylic acid). In this bphA (bphA1A2A3A4), bphA1 (2072) evolved by family (DNA) shuffling, which has a wide substrate preference, was used. Many of the converted compounds were novel, and some of them showed potent antioxidative activity.
Circadian rhythmic plant leaf-movement, called nyctinasty, is controlled by a time-course change in the internal concentration of the leaf movement factors (leaf-opening and leaf-closing substances) in the plant body. We revealed that the target cell for the leaf-movement factors is plant motor cell by using novel synthetic fluorescence labeled probes. Using photoaffinity probes 21, the specific binding proteins for potassium lespedezate 1, the leaf-opening substance of Cassiamimosoides L, are detected from the plasma membrane fraction of the plant motor cell. Our study is a rare successful result of the detection of membrane receptors by using a synthetic photoaffinity probe designed on a biologicallly active natural product. These results also advance a guideline for probe design towards successful photoaffinity labeling. The balance of concentration of the leaf movement factors is inversed during the day. The glycoside type leaf movement factor is hydrolyzed with β-glucosidase, the activity of which is regulated by the biological clock. The circadian rhythm observed in the leaf movement is introduced by activation of the β-glucosidase regulated by the biological clock. We synthesized the glyconoamidine gel 43 designed on potassium lespedezate, a glycoside type leaf-opening substance, and succeeded in purification of the β-glucosidase, a key enzyme of circadian rhythmic plant leaf-movement, by affinity chromatography using affinity gel 43.
Nickel catalyst promotes the homoallylation of aldehydes and ketones with 1, 3-dienes in the presence of triethylborane and diethylzinc as reducing agents to provide bishomoallyl alcohols with high regio-and stereoselectivities. In place of diethylzinc, dimethylzinc serves as a methylating agent to evoke the three-component coupling reaction of methyl group, 1, 3-dienes, and carbonyls to provide 3-hexenols in excellent yields. Furthermore, nickel catalyzes the four-component connection reaction of carbonyls, 1, 3-dienes, alkynes, and dimethylzinc in this order to furnish 3, 6-octadien-1-ols. A combination of palladium catalyst and triethylborane induces allylic alcohols to undergo the nucleophilic allylation of aromatic aldehydes to provide homoallyl alcohols. By the addition of lithium chloride and triethylamine to the Pd catalyst/triethylborane system, aliphatic aldehydes undergo the electrophilic allylation with allylic alcohols at the α-carbon of aldehydes to give α-allylated aldehydes. Under similar conditions, 2-methylenepropane-1, 3-diol can be utilized as a synthetic equivalent of a zwitterionic trimethylenemethane species to bring about the sequential amphiphilic allylation.
In recent years, a variety of chemical methods for selective labeling or functional modulation of protein of interest has been developed. In this article, we focus on synthetic organic chemistry for protein modification, especially on the recent developments of the bioorthogonal reactions, which enable to hybridize an artificial small molecule to a protein of interest with a site-selective manner. On the other hand, covalent bond formation of protein with a small molecule has also been recognized as a powerful strategy to regulate protein functions, and enormous efforts have been devoted to develop selective irreversible inhibitors for proteins, especially for the families of proteases, in the research field of medicinal chemistry. We also provide an overview of the irreversible inhibitors, including their recent advancements and some applications for proteome analysis or drug discovery. In addition, we report herein our original method (P-PALM) for site-selective modification of a protein using the photo-affinity labeling technique. The utility of the P-PALM method has been successfully demonstrated in the modifications of the lectin into the new fluorescent saccharide biosensors.
Optically active seleninic acids and a tellurinic acid were obtained by chromatographic resolution on chiral columns or chiral crystallization, and their chiroptical properties and absolute configurations were determined. Kinetic studies of the racemization, oxygen exchange reaction using H218O, and theoretical studies clarified that optically active sulfinic acids and seleninic acids racemize via an achiral chalcogeninate anion, whereas optically active tellurinic acids racemize via an achiral diol cation or an achiral hypervalent hydrate (tellurane). Optically active seleninamides and seleninate esters were also isolated by chromatographic resolution, and their chiroptical properties and absolute configurations were determined. The optically active seleninamides and seleninate esters without bulky substituents were found to be unstable toward racemization. Both of the optically active seleninamides and seleninate esters were found to racemize via an achiral hypervalent hydrate (selenurane)