Pyraflufen-ethyl [ethyl 2-chloro-5- (4-chloro-5-difluoromethoxy-l-methylpyrazol-3-yl) -4-fluo-rophenoxyacetate] is a potent Protox inhibiting cereal herbicide. It was discovered by Nihon Nohyaku Co. Ltd. through a series of synthetic research on biologically active compounds, the lead compound of which was synthesized by utilization of ketene dithioacetal chemistry extended by Nihon Nohyaku. Pyraflufen-ethyl controls troublesome broad-leaved weeds including Galium aparine at a rate of 6-12 g a.i./ha in post-emergence application. It was introduced into the mar-ket in 1999, and is now utilized as the active ingredient for a cereal herbicide and for a total vege-tation control herbicide in combination with another active ingredient in Japan and will be launched worldwide in near future. This paper describes the characteristics of this herbicide and the background of discovery including lead generation and lead optimization, as well as the process chemistry of this unique herbicide. It is noted that the manufacturing process was dramatically improved by the application of the Heck reaction and the Friedel-Crafts reaction to the process chemistry.
The chemistry of allenylpalladium and propargylpalladium has been developed to construct use-ful catalytic reactions in organic synthesis. However, the reaction mechanism has not been under-stood well due to the lack of the systematic studies on the allenyl and propargyl complexes of pal-ladium. Thus, the correlation between the coordination mode and the reactivity of η1-allenyl, η1-propargyl, η3-allenyl/propargyl and, μ-η3-allenyl/propargyl ligand on palladium or platinum was revealed. Moreover, these coordination modes can be interconverted one another very easily under certain conditions. This easy interconversion generates an intermediate having different coordination mode, which can not be observed but plays a very important role in the key reactions in catalytic cycles, such as isomerization, oxidative addition, and racemization.
Boron-mediated aldol reaction of carboxylic esters is described in detail. Contrary to the gener-al belief that carboxylic esters are inert toward the conventional enolization conditions, propionate esters are shqwn to have adequate reactivity on the boron-mediated aldol reaction. More impor-tantly, the stereochemical course of the aldol reaction can be controlled by the judicious choice of the enolization reagents. Complementary anti- and syn-selective asymmetric aldol reaction of structurally related chiral esters are developed. Also, novel double aldol reaction is discovered with acetate esters, which provides a precursor to the synthesis of chiral triols of C3-symmetry. Extensive NMR experiments lead to characterize the first carbon-bound boron enolates and the novel doubly borylate enolates as intermediates of the double aldol reaction. A plausible mecha-nism of the double aldol reaction is proposed.
Daphniphyllum alkaloids with unique heterocyclic ring systems are of current interest from a biogenetic point of view or as challenging targets for total synthesis. Recently, many Daphniphyllum alkaloids indicating the unique biogenetic path have been isolated.
Although many recent studies have established that nitric oxide (NO) is an important bioregulatory agent of the smallest size in a range of physiological processes from vasodilation and platelet aggregation to neurotransimission and immune system, possible indirect contribution of endogenous and induced NO carriers, i.e., NO donors, is recently highlighted. Generally the physiological concentration of free NO is very low. In order to understand uncovered Janus-faced actions of NO, and reorganize complicated contribution of the isoforms of nitric oxide synthases (NOS), structural design and synthesis of novel NO donors, which can realize controlled release of NO or NO equivalents in terms of the rate and place (i.e., targeting), are desired. Herein we review briefly the recent studies about the chemical natures of potential NO donors, particularly of S-nitrosothiols and N-nitrosamines. The latter compounds can be considered as potential NO/NO+ donors. However, the relation of the structures of N-nitrosamines, in particular of aliphatic N-nitrosamines, to the characteristics of release of NO or NO+ remains unclear. A new category of NO donors based on the N-nitrosoamines of 7-azabicyclo [2.2.1] heptanes was described. These compounds can undergo heterolytic N-NO bond cleavage. The postulate that N-NO bond cleavage of N-nitrosamines is enhanced by a reduction of the resonance in the N-NO group arising from the structural features is proposed.
Guanidines easily react with not only acidic compounds but also electrophiles such as alkyl halides, to form the corresponding stable salts due to effective resonance. Thus, modified guani-dines could be expected to play important roles as chiral auxiliaries in asymmetric synthesis if chi-ral environment is produced in reactive salt intermediates. This article reviews the preparation of modified guanidines and their application to asymmetric synthesis. Reasonable asymmetric induc-tions were observed not only in catalytic but also in stoichiometric asymmetric syntheses. These guanidine-mediated reactions may contribute to development of green chemistry because of their possible uses as recyclable (economically favored) and easily functionalizable (widely applicable) auxiliaries.
Brain Ischemia is believed to induce neuronal damage by causing a [Ca2+] i overload and a sustained increase in the level of extracellular glutamate (Excitotoxicity theory). Based on the Excitotoxicity theory, inhibition of neuronal voltage-dependent calcium channels is expected to reduce excessive glutamate release at the presynaptic terminals, inhibit [Ca2+] i elevation in postsynaptic neurons, and protect neurons from cell death. E2050, which is derived from Verapamil, a known L-type calcium channel blocker, is a newly synthesized neuronal calcium channel blocker discovered at Eisai Tsukuba Research Laboratories. E2050 is an optically active compound in which the quaternary carbon center has a 2-isopropyl-2-phenyl-5-piperazinopentanitrile substituent. We report here two general routes for the preparation of enantiomerically pure E2050. First, we describe the preparation of the chiral 5-hydroxy-2-isopropyl-2-phenylpentanitrile which is the key intermediate by enzyme-catalyzed kinetic resolution. Second, we illustrate the practical asymmetric synthesis of E2050 by Sharpless epoxidation followed by MAD-induced rearrangement. We believe these methods are suitable for large-scale synthesis of E2050.