As successive discoveries were made of thromboxane A2, prostacyclin, and the leukotrienes from 1975 to 1979, the physiological and pathological roles of the arachidonate cascade metabolites were clarified. With these discoveries as a turning point, novel concepts for designing new drugs which specifically control and manipulate the metabolites have rapidly grown and developed. Any new approach to treating and preventing cardio- and cerebro- vascular diseases requires urgent and careful evaluation. Recent research into thromboxane synthetase inhibitors (TXSI) and thromboxane receptor antagonists (TXRA) has focussed attention mainly on platelets and blood vessel walls, and the interaction between the two. Some TXSI and TXRA have been studied in a variety of in vitro systems and animal models, and are now in various stages of clinical evaluation. In the present review, TXSI, TXRA, and the structure-activity relationships are described together with the results of our experiments on this subjects.
Recent studies have shown that chemically synthesized petides representing a part of the surface of a protein can elicit antibodies reactive with the native molecule. Some of the antibodies thus obtained are also shown to have activities to neutralize viruses, when the peptide constituting the surface antigen of the virus are used for immunization. Such peptides have potentials to serve as synthetic vaccines and several successful results have been reported. In order to use synthetic peptide vaccines for humans and domestic animals, we have to consider the following factors; 1) selection of the peptides, 2) carriers of the peptides, 3) adjuvants, 4) contribution of cellular immunity.
Various novel flavour and fragrance chemicals have been synthesized day by day. The specialized needs on new flavour and fragrance chemicals are quickly increasing in response to the rapid spread of plentiful human life styles. Therefore, the recent trend of Japanese market on natural and synthetic flavour and fragrance chemicals and their compounds are reviewed at first, and newly developed synthetic routes of important flavour and fragrance chemicals and many interesting new chemicals opened mainly on Japanese patent were summarized.
Extensive research has been done to get the ideal “third generation insecticides” in the area of compounds showing insect juvenile hormone (JH) activity since the discovery of JH activity in insect extracts. Although some JH mimics have been commercialized and practically used as proper insecticides in some specific fields, it has become apparent that researchers have now recognized the inherent disadvantage of JH mimics as insecticides and they do not seem to have such enthusiasm that they showed once. Here, I would like to present a brief review of JH and JH mimics as well as a prospective view of insecticidal JH mimics, while showing the recent JH active compounds discovered in our laboratory.
Organic molecules with polyhedral symmetry have been and remain a challenge to organic chemists. Among hydrocarbons based on Platonic solids, cubane (Oh symmetry) was prepared by Eaton and Cole in 1964 and dodecahedrane, which exhibits the highest symmetry (Ih) ever imagined for any organic compound, was made by Paquette and co-workers in 1982. Tetrahedrane (Td symmetry), the “simplest” of the Platonic hydrocarbons, is unknown but the tetralithio and the tetra-tert-butyl derivatives were prepared in 1978 by the Schleyer group and the Maier group, respectively. Among molocules with chiral polyhedral symmetry (T, O, and I symmetry), the existence of molecules with conformational T symmety has been discussed by several workers. The first experimental proof of the existence of the conformational T symmetry molecule was given by Bartell and co-workers in 1970. The synthesis of the first optically active organic molecule with T symmetry has been accomplished by our group in 1982. As far as I know, organic molecule belonging to the O and I point group is still unknown.
New approaches to the heterocyclic syntheses through pericyclic reactions are presented in three sections. (1) The utility of (phenylsulfonyl) propadiene (1) as an allenic dienophile and/or electrophile was revealed by its facile intermolecular cycloaddition reactions with electron-rich dienes, tropone, azaheptafulvenes, and thebaine derivatives, which afforded various heterocyclic compounds including some novel ring systems. (2) trans-4- (Phenylsulfinyl) -3-buten-2-one (29) underwent a new versatile addition-elimination (trans-vinylation) reaction with five-membered heterocycles such as furans, pyrroles, imidazole, pyrazole, and 6- (dimethylamino) fulvene to give excellent yields of the corresponding vinylated compounds. This method combined with the intramolecular Diels-Alder reaction was applied to the synthesis of linearly condensed tricyclic heterocycles like psoralen (31) and the novel aza-analogue of psoralen (38). (3) Intramolecular cycloaddition (ex., Diels-Alder reaction) using allenic dienophiles proceeded with extraordinary ease due to their favorable geometry. These reactions were successfully utilized in the development of new polycyclic lactone synthesis, furan ring transfer (FRT) reactions, tandem intramolecular [2+2] -cycloaddition, [3, 3] -sigmatropic rearrangement, and indole synthesis. Application of some of these new methods to the natural products synthesis is also described.