Natural products, isolated as secondary metabolites of such marine origins as sponge, alga and sea hare, have served new and various structures with a variety of bioactivity. Since 1970, the phenylpyruvic acid oxime derivatives have widely been isolated as a main group of marine natural products containing bromine atoms. This family has potent bioactivities such as antimicrobial, antitumor, antifeedant activities, and so on. Synthetic studies on phenylpyruvic acid oxime derivatives are described. Among them, the phenolic oxidation has been recognized as one of important methods to synthesis of bastadines and spiroisoxazolines.
The demand for 2'-deoxynucleosides is increasing rapidly in the fields of gene therapy, biological research, and medical diagnosis. Development of an efficient synthetic method has been expected over the past few decades. We developed a novel synthetic method applicable to industrial manufacture of all four natural 2'-deoxynucleosides. Chemically synthesized 2-deoxyribose 1-α-phosphate (dRP) was enzymatically converted to thymidine (T), 2'-deoxycytidine (dC), 2'-deoxyadenosine (dA), and 2'-deoxyguanosine (dG) in the presence of nucleoside phosphorylase. This chemo-enzymatic method consists of three distinctive technologies : (i) stereoselective synthesis of dRP by crystallization-induced asymmetric transformation; (ii) an efficient method to expedite enzymatic conversions by adding Mg (OH)2; (iii) development of a new enzyme for the enzymatic synthesis of dC.
This article is focused on the chiral Lewis acid catalyses by the optically active ketoiminatocobalt complexes. Screening of the central metal of the ketoiminato complex catalysts for the enantioselective hetero Diels-Alder reaction revealed that cobalt was the most effective for affording the corresponding pyranone derivatives. The corresponding cationic cobalt (III) complexes were developed as an efficient Lewis acid catalyst and subjected to the hetero Diels-Alder reaction and the carbonyl-ene reaction. It was found that their counter anions significantly influenced the reactivity and the enantioselectivity in the carbonyl-ene reaction. The cationic cobalt (III) complexes could be employed as the efficient catalysts for the enantioselective 1, 3-dipolar cycloaddition reaction. Because of the competitive coordination of the nitrone, the 1, 3-dipolar cycloaddition with the monodentate α, β-unsaturated aldehyde has been limited to several catalyses, although these cationic cobalt (III) complexes effectively catalyzed the reaction to afford the isoxazoline derivative with high-to-excellent stereoselectivities. These types of cobalt complex catalystscould be applied to the enantioselective Henry reaction even in the Presence of amine baces and the enantioselective chemical fixation of carbon dioxide to obtain the optically active cyclic carbonate.
Synthesis of wholly aromatic polyketones, i.e., polymers having backbones consisting of aromatic rings and ketonic carbonyl groups, via electrophilic aromatic acylation reaction and/or nickel complex-mediated aromatic coupling polymerization has been developed. Introduction of 2, 2'-dimethoxy-5, 5'-biphenylene, 2, 2'-diaryloxybiphenylene, or o-terphenylene skeletons affects formation of high molecular weight polyketones. In particular, wholly aromatic polyketones composed of 2, 2'-bis (4-benzoylphenoxy) -5, 5'-biphenylene or o-terphenylene skeletons show high thermal resistibility and excellent solubility in organic solvents.
Arynes were found to insert into carbon-tin σ-bonds of organostannanes with the aid of a palladium-iminophosphine catalyst, whereas a palladium-tert-alkyl isocyanide complex efficiently catalyzed the addition of cyclic disilanes (silicon-silicon σ-bonds) or distannanes (tin-tin σ-bonds). Owing to the highly electrophilic character of arynes, insertion reactions of arynes into ureas (nitrogen-carbonyl σ-bonds) or stannyl sulfides (sulfur-tin σ-bonds) took place without an added catalyst, where zwitterions arising from nucleophilic addition of the nitrogen or sulfur atom to arynes acted as key intermediates. Furthermore, arynes also accepted the nucleophilic addition of carbene moieties of isocyanides to form 1, 4-dipoles, which were convertible into iminoisobenzofuran or iminoisoindoline via the action with third components (aldehydes or N-tosylaldimine).
α-Hydroxy-β-amino acids are well known as inhibitory machinery for the development of protease inhibitors. In our ongoing efforts to develop effective aspartic protease inhibitors such as HIV-1 protease, malaria plasmepsin and human β-secretase inhibitors, the α-hydroxy-β-amino acids are also the critical core structures. In addition, the unique structure of these amino acids, in which three different functional groups, i.e. amino, hydroxyl and carboxyl groups, are located on the two adjacent asymmetric carbon atoms, also has interesting features to create new functional molecules useful in both organic chemistry and medicinal chemistry. In this article, organic and medicinal chemical applications based on the chemistry of α-hydroxy-β-amino acids will be presented, including 1) byproduction of homobislactone during the carboxyl group activation of N-protected-α-hydroxy-β-amino acids, 2) development of α-hydroxy-β-amino acid derived new solid-supported Evans' chiral auxiliary for asymmetric synthesis, 3) development of a novel and efficient method for the synthesis of difficult sequence-containing peptides, and 4) O-N intramolecular acyl migration of α-hydroxy-β-amino acids for the development of water-soluble prodrugs of taxoids (isotaxoids).