Synthesis of pheromones, hormones and other bioregulators is discussed summarizing Mori's synthesis of optically active and naturally occurring compounds of biological interests. The reason why Mori began his enantioselective synthesis of natural products is discussed first in connection with the synthesis of (±) -gibberellin A4, (±) -kaur-16-en-19-ol, (±) -juvenile hormone I and (±) -juvabione. His subsequent synthesis of optically active grasshopper ketone and pheromones is then briefly discussed. Application of biocatalysis to enantioselective synthesis, Mori's hall-mark, is summarized to emphasize the usefulness of biocatalysis in synthesizing optically active compounds such as pheromones. The relationships between stereochemistry and pheromone response are summarized. Diversity is the key word of pheromone response. Several examples are given to illustrate that some natural products are optically impure. Finally, recent examples of Mori's pheromone synthesis are given in the cases of (4R, 9Z) -9-octadecen-4-olide (the female sex pheromone of the currant stem girdler) and the stereoisomers of 9-acetoxy-19-methylnonacosane (the female sex pheromone of the screwworm fly).
Catalytic addition of carbon-hydrogen bonds to olefins and acetylenes takes place with the aid of transition metal complexes. Coordination of a heteroatom to the metal is important for attaining both the C-H bond cleavage and the C-C bond formation.The C-C bond formations occur exclusively at the position ortho or the position β to the directing group. Various aromatic and olefinic compounds such as ketones, esters, aldehydes, imines, imidates, hydrazones, and nitriles can be used in this coupling reaction.The mechanistic studies of the ruthenium-catalyzed reaction of aromatic esters with olefins revealed that there is a rapid equilibrium prior to the C-C bond formation and the C-C bond formation is rate-determining. Catalytic arylation of C-H bond in aromatic ketones with organoboronates gave the ortho arylation products in high yield. The chelation-assisted C-H bond cleavage protocol is also applicable to the regioselective silylation of aromatic C-H bonds with hydrosilanes or vinylsilanes. Various aromatic and heteroaromatic compounds can be used in the silyaltion reaction.
During the past decade, much attention has been directed toward the development of potassium channel blockers, which were expected to be a novel type of antiarrhythmic agent. Pharmacological screening for new cardiovascular agents led us to discover the potassium channel blocking activity of MS-3579 which we originally prepared as a β-blocking agent. Since MS-3579 lacks potency as a class III agent and its (aryloxy) propanolamine moiety was thought to be the typical β-blocking pharmacophore, we decided to manipulate this moiety to diminish β-blocking activity and potentiate class III activity. In this paper we introduce the development of Nifekalant Hydrochloride, which selectively modulates potassium channel and homogeneously prolongs the transmembrane action potential duration (APD) and consequently, refractoriness, without slowing intercardiac condition, and can terminate reentry. Nifekalant Hydrochloride was approved and launched as the first class III antiarrhythmic agent, developed in Japan.
Kinamycin antibiotics, strongly active against gram-positive bacteria, were isolated from the culture broth of Streptomyces murayamaensis. Their structures were firstly determined to be a benzo [b] carbazoloquinone skeleton with N-cyanamide [N-C≡N] moiety. After that, prekinamycin was isolated from the same organism as a biosynthetic precursor and the same 6-6-5-6 ring system was also proposed for the structure. But problems still remained on the determination of substituent pattern at N-cyanamide moiety by spectroscopic means. Recently, the structures of kinamycins and prekinamycin were revised to be a benzo [b] fluorene skeleton with diazoalkane moiety [C--N+≡N]. However, a synthetic compound with the revised structure for prekinamycin was found to be different from natural prekinamycin, instead an isomeric benzo [a] fluorene skeleton, a 6-5-6-6 ring system was proposed for the natural product, which was newly named as isoprekinamycin. Herein the chemistry of kinamycins and their related compounds with structural confusions is reviewed, especially focused on the history of structural determination and recent synthetic studies.
The first chiral isoxazoline ligands bearing spiro skeleton are developed. The spiro bis (isoxazoline) ligands (SPRIXs) are readily synthesized from diethyl malonate via double intramolecular nitrile oxide cycloaddition as a key step. The complex of (M, S, S) -R-SPRIX and Pd (OCOCF3)2 promoted the catalytic asymmetric Wacker-type cyclization of alkenyl alcohols to give optically active cyclic ethers for the first time. Furthermore, starting from dialkenyl alcohol, the enantioselective tandem cyclization via oxy-palladation was achieved with up to 95% ee. Asymmetric ligands other than SPRIXs promote neither the Wacker-type reaction nor the tandem reaction.