A total synthesis of (+) -leinamycin (1), a unique sulfur-containing antitumor antibiotic, is described. The present synthesis features a stereocontrolled construction of the macrolactam followed by a spiroannulation of the hitherto unprecedented dithiolanone ring.

View full abstract

Axially chiral monophosphines, 2- (diphenylphosphino) -2′-methoxy-1, 1′-bi-naphthyl (MeO-MOP, la) and its biphenanthryl analog 5 were prepared starting with homochiral 2, 2′-dihydroxy-1, 1′-binaphthyl and 3, 3′-dihydroxy-4, 4′-biphenanthryl, respectively. The palladium complexes coordinated with the MOP ligands are highly effective catalysts for several types of catalytic asymmetric reactions where chelating bisphosphine ligands can not be used because of their low catalytic activity or low selectivity towards the desired reaction pathway. The catalytic asymmetric reactions are : 1) Asymmetric hydrosilylation of alkylsubstituted terminal olefins and bicyclo [2.2.1] heptene derivatives giving, after oxidation, optically active alcohols (95% ee). 2) Asymmetric 1, 4-hydroboration of 1, 3-enynes giving axially chiral allenylboranes (61% ee). 3) Asymmetric reduction of allylic esters with formic acid (up to 93% ee).

View full abstract

In view of the ever expanding repertoire of Lewis acids available as proton substitutes in current synthetic organic methodology, our goal was to engineer an artificial proton substitute possessing unique topology; effective as an artificial enzyme for chemical reactions, by harnessing the high reactivity of the metal atom towards oxygen and nitrogen. Such a concept was realized by examining the recognition ability of specially designed metal receptors for various oxygen- and nitrogen-containing substrates.

View full abstract

By utilizing the phenomenon that molecules move from crystal to crystal quite easily under appropriate conditions, a new type of organic chemistry has beencontrived. The combination of the enantioselective molecular movement from racemic guest crystal to chiral host crystal with fractional distillation, leads to a process whereby enantiomeric guest molecules can be separated by distillation. Selective and efficient organic reactions can be carried out by grinding crystals of substrate and reagent.

View full abstract

A variety of substituted cyclopropenone acetals have been prepared and studied for the purpose of gaining further insights into their organometallic and thermal chemistry. Acidic hydrolysis of the acetals gave the corresponding cyclopropenones, among these are a naturally occurring cyclopropenone antibiotic, penitricin. A new class of cysteine protease inhibitor can be realized if the penitricin moiety is contrived as a dipeptide-like binding site. Thermolysisbf substituted cyclopropenone acetals generates vinyl carbene species that undergo [1 + 2] and [3 + 2] cycloadditions to electrondeficient olefins. The cyclopropenone acetal also serves as a precursor to a dipolar trimethylenemethane. The vinyl carbene and the trimethylenemethane species undergo cycloaddition to give buckminsterfullerenes, with which the various organic derivatives of fullerenes generated have been shown to exhibit photo-induced cytotoxicity, DNA cutting activity and enzyme inhibition.

View full abstract

Computer-aided conformational analysis and design of key intermediates in the stereoselective and efficient synthesis of macrolides were successfully applied to synthetic studies of 1) erythronolide A, 2) carbonolides, leuconolides and maridonolides, 3) halichondrin B, and 4) tedanolide.

View full abstract

The asymmetric Heck reaction, which we achieved for the first time several years ago, has been successfully applied to catalytic asymmetric syntheses of many bioactive molecules such as vernolepin, γ-butyrolactone derivatives, eptazocine, a halenaquinol skeleton and lentiginosine.

View full abstract

C-Glycosidation is of great significance since it contains the introduction of carbon chains to sugar chirons or sugar nuclei as chiral pools. Silylacetylenes are sufficiently reactive to form sugar acetylenes for the selective introduction of acetylenic groups to sugar rings. Bis-C-glycosidation allows introduction of two sugars at both ends of a bis (trimethylsilyl) acetylene. A 2, 3-dideoxyglucose derivative provided the corresponding C-1 α acetylenic compounds, which would increase the scope of C-glycosidation with silylacetylenes. An alkynyl group attached to the anomeric position of a pyranose ring was epimerized through a dicobalthexacarbonyl complex by treatment with trifluoromethane sulfonic acid. Three steps involving cobalt complexation, acidic transformation and decomplexation afforded overall epimerization and thus prompted us to provide either the α or β alkynyl C-glycoside as desired. Ring opening of a dihydropyran derivative using Nicholas-type cation intermediates was also an accomplished part of this study.

View full abstract

Design, synthesis, and chemistry of neocarzinostatin chromophore analogs and their DNA cleaving abilities have been discussed. A Three dimensional solution structure of neocarzinostatin complex explicitly shows how the neocarzinostatin apoprotein binds and prevents the chromophore from decomposing. The suggested binding elements and stabilization mechanisms have been examined by the model studies.

View full abstract

Some ruthenium complexes have been found to catalyze the direct addition of ortho carbon-hydrogen bonds in aromatic ketones to olefins with high efficiency and selectivity.

View full abstract