Studies on the syntheses of hetrocyclic and natural compounds. part 948: A simple and convenient synthesis of yohimbane and alloyohimbane

A simple method for the stereoselective synthesis of yohimbane (7) and alloyohimbane (5) via the diazoketone (2) from the anhydride (8), a symmetrical starting material, was examined. The preparation of pentacyclic ring systems contained in yohimbine and reserpine would be possible for the synthesis of such alkaloids by this method.     

Enantiomerically pure 2-bromo-2'-diphenylphosphinyl-1,1'- binaphthyl as a monophosphorus template for electrophilic functionalization in chiral MOP-type ligand synthesis

[reaction: see text] Pd-catalyzed monophosphinylation of (R)-2-bromo-2'-iodo-1,1'-binaphthyl with Ph(2)P(O)H afforded (R)-2-bromo-2'-diphenylphosphinyl-1,1'-binaphthyl in good yield with excellent chemoselectivity and no observable racemization. Subsequent lithiation in the presence of excess thiosulfonate furnished an enantiomerically pure sulfenylation product, which was reduced to afford a chiral S-MOP ligand.     

Studies on the syntheses of heterocyclic compounds. Part CDXCVII. Total syntheses of (±)-cryptaustoline and (±)-thaliporphine by the benzyne reaction

The indisputable benzyne reaction of 1-(5-bromo-3,4-dimethoxybenzyl)-1,2,3,4-tetrahydro-7-hydroxy-6-metlioxy-2-methylisoquinoline (II) with sodium amide in liquid ammonia afforded the following compounds, (±)-cryptaustoline iodide (VI), (±)-thaliporphine (VIII), 1 -(3,4-dimeth-oxybenzyl)- (III), and 1 -(2-amino-4,5-dimethoxybenzyl)-l,2,3,4-tetrahydro-7-hydroxy-6-meth-oxy-2-methylisoquinoline (IV).     

Triplet diphenylcarbenes protected by (trimethylsilyl)ethynyl groups

(2,4,6-Tribromophenyl)(4-tert-butyl-2,6-dimethylphenyl)diazomethane (1a) was shown to be stable enough to survive Sonogashira coupling reaction conditions at an elevated temperature and gave not only a para-monosubstituted product, (4-trimethylsilylethynyl-2,6-dibromophenyl)(4-tert-butyl-2,6-dimethylphenyl)diazomethane (1b), but also a disubstituted one, [2,4-bis(trimethylsilylethynyl)-6-bromophenyl](4-tert-butyl-2,6-dimethylphenyl)diazomethane (1c), and a trisubstituted product, [2,4,6-tris(trimethylsilylethynyl)phenyl](4-tert-butyl-2,6-dimethylphenyl)diazomethane (1d). Triplet diphenylcarbenes (DPCs) generated by photolysis of those ethynylated diphenyldiazomethanes were characterized by ESR and UV-vis spectroscopies at low temperature and laser flash photolysis techniques in solution at room temperature. Although ESR data indicated that ethynyl groups at the ortho positions are likely to stabilize triplet DPCs both sterically and electronically more effectively than o-bromine groups, kinetic studies suggested that the stability of triplet DPCs is not increased by o-ethynyl groups, as opposed to o-bromine groups. It is likely that triplet DPCs decay by interacting with the o-ethynyl groups.     

Frequency Dependence of ESR in Pristine Trans-Polyacetylene: Line Width

We measured a frequency dependence of ESR line width in (CH)x and (CD)x at frequencies 5～9,500 MHz. From a detailed analysis we could independently deduce 1-D diffusion rate of electron spin (neutral soliton) D_‖ /c_‖ ², and the trapped spin concentration C between 200 and 340 K.     

Total Synthesis of Mallotusinin

The total synthesis of mallotusinin, which bears a tetrahydroxydibenzofuranoyl (THDBF) bridge between the 2-oxygen and 4-oxygen of glucose on corilagin with a 3,6-O-(R)-hexahydroxydiphenoyl (HHDP) bridge, is described. The key features of the total synthesis are: 1) improvements of our previously reported method to synthesize corilagin; 2) establishment of the THDBF skeleton via an unusual intramolecular S_NAr reaction of an HHDP analogue, and 3) the application of a two-step bislactonization strategy for a HHDP bridge construction into the 2,4-O-THDBF bridge. Oxidative phenol coupling of 1,2,4-orthoacetyl-3,6-di-(4-O-benzylgalloyl)-α-d -glucopyranose and the orthoester cleavage of the coupling product without the pyranose-furanose ring transformation are key reactions for the improved synthesis of corilagin, which enabled the adequate supply of a corilagin precursor that was required to develop the mallotusinin synthesis. These established methods are expected to help develop the synthesis of other ellagitannins with a bridge between the two oxygens of corilagin.     

Indium-Catalyzed C−F Bond Transformation through Oxymetalation/β-Fluorine Elimination to Access Fluorinated Isocoumarins

Fluorinated heterocycles have attracted much attention in the pharmaceutical and agrochemical industries. Many strategies have already been developed to achieve the synthesis of fluorinated heterocycles. Formidable challenges remain, however, in the synthesis of fluorinated isocoumarin derivatives that are among the most alluring structural motifs. Herein, the indium-catalyzed C−F bond transformation of 2-(2,2-difluorovinyl) benzoates is reported, which are readily accessible compounds, to give a diverse array of fluorinated isocoumarins. The present reaction proceeds smoothly using inexpensive reagents: a catalytic amount of indium salt in the presence of zinc salt. A theoretical calculation of potential energy profiles showed that the reaction consists of oxymetalation with the elimination of alkyl halide and the β-fluorine elimination.     

Restriction landmark genome scanning method using isoschizomers (MspI/HpaII) for DNA methylation analysis

Restriction landmark genome scanning (RLGS) is a 2-DE of genomic DNA, which visualizes thousands of loci. In a conventional RLGS method for methylation analysis, we have used a methylation sensitive restriction enzyme, NotI as a landmark. However, it was unable to discriminate methylation polymorphism from sequence polymorphism. Here, we report an improved RLGS method to detect methylated sites directly. We employed isoschizomers, MspI and HpaII, that recognize the same sequence (CCGG) but have different methylation sensitivity. We carried out the RLGS analysis of Arabidopsis thaliana ecotype Columbia, and obtained a pair of spot patterns with MspI and HpaII. We detected 22 spots in both patterns. In comparison of them, 18% of the spots were polymorphic, which indicated the methylation of C(5m)CGG sites. Further analyses revealed an additional methylated site of NotI. Moreover, 52 and 54 restriction enzyme sites were also analyzed in two other ecotypes, Wassilewskija and Landsberg erecta, respectively. Consequently, 15% of the 52 common sites showed methylation polymorphism among the three ecotypes. The restriction sites analyzed in this study were located in or near genes, and contribute new data about the correlation between methylation status and gene expression. Therefore, this result strongly indicates that the improved RLGS method is readily applicable to practical analyses of methylation dynamics, and provides clues to the relationship between methylation and gene expression.     

Development of an analytical method using microchip capillary electrophoresis for the measurement of fluorescein-labeled salivary components in response to exercise stress

We have developed an analytical method using microchip capillary electrophoresis (microchip CE) for the high-speed separation of fluorescein-labeled salivary components in response to exercise stress. Optimal separation was obtained using a borate buffer at pH 9.5 containing 10 mM beta-cyclodextrin and 1.0% (w/v) methylcellulose. To minimize individual differences in human saliva, such as viscosity, conductivity, and contaminants, the concentration of methylcellulose in the analytical conditions played a key factor. The optimized separation conditions produced identical electropherograms successfully despite of the use of different microchips made from quartz glass or poly-methylmethacrylate (PMMA). In addition, a practical application of bicycle ergometer stress was performed. Some components in human saliva showed a marked decrease after exercise stress.