New Chiral Kemp's Acid Diamides for Chiral Amine Recognition by 1 H NMR

Two Kemp's acid diamides were synthesized and applied to chiral amine recognition using ¹H NMR analysis. One derivative based on 1-(1-naphthyl)ethylamine had good chiral recognition of six amines and was useful to determine the optical purity for three amines, i.e., methylbenzylamine, 1-(1-naphthyl)ethylamine and 1- henylpropylamine,however, the cyclohexylethylamine derivative showed little discrimination for the amines studied. Together with the results for alkylamines, it was shown that aromatic structure was important for aromatic shielding anisotropy and –– interactions between host and guest. The structure of the 1-(1-naphthyl)ethylamine derivative in solution was also considered based on ¹H NMR data and computer simulation.     

Effects of natural polysaccharide addition on drug release from calcium-induced alginate gel beads

Calcium-induced alginate gel beads (Alg-Ca) containing various polysaccharides, including an alginate hydrolysate, were prepared and the drug release profiles were investigated. Hydrocortisone (HC) was gradually released from Alg-Ca into the mimic gastric fluid, while in intestinal fluid, it was quickly released with the dissolution of Alg-Ca. However, with Alg-Ca containing 5% chitin (CT), dissolution of Alg-Ca was not observed, and release of HC showed apparent zero-order kinetics. Furthermore, addition of the alginate hydrolysate altered the HC-release profile for Alg-Ca.     

Difference in electrophoretic mobility and plasmic digestion profile between four recombinant fibrinogens, gamma 308K, gamma 308I, gamma 308A, and wild type (gamma 308N)

We have produced recombinant gamma-chain variant fibrinogens, gamma308K, gamma308I, and gamma308A simultaneously with wild-type fibrinogen, gamma-308N, by genetic protein engineering using Chinese hamster ovary cells. Although all three variant fibrinogens are a result of a single amino acid substitution, the aberrant gamma-chains of gamma308K and gamma308I fibrinogens migrated faster than gamma308N. Furthermore, plasmic digestion profiles were examined in the presence of 5 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) or 1 mM CaCl2. In the presence of EGTA, the three variant fibrinogens were digested into D1 and D2 fragments slightly faster than wild type. In addition, the D2 fragment derived from gamma308K was further digested into D3 by plasmin much faster than that from gamma308N. These data suggest that cleavage of gamma356Lys-gamma357Ala bond by plasmin in gamma308K, gamma308I, and gamma308A is slightly accelerated and the gamma302Lys-gamma303Phe bond is cleaved by plasmin rapidly in only the gamma308K variant. Furthermore, the substitution of Lys for gamma308Asn results in the generation of a new plasmin cleavage site between gamma308Lys and gamma309Gly in the presence of EGTA. In conclusion, a substitution at residue gamma308Asn may cause a conformational change in the gammachain of fragment D affecting polymerization and plasmin cleavage.     

Inhibitory effects of glycyrrhetic acid derivatives on 11 beta- and 3 alpha-hydroxysteroid dehydrogenases of rat liver.

Glycyrrhetic acid (GA), an aglycone of glycyrrhizin (GL), is a potent inhibitor of 11 beta- and 3 alpha-hydroxysteroid dehydrogenases. 11 beta-Hydroxysteroid dehydrogenase activity of rat liver microsomes was potently inhibited by GA, 3-deoxyglycyrrhetic acid (3-deoxyGA), 3-ketoglycyrrhetic acid (3-ketoGA), 3-epiglycyrrhetic acid (3-epiGA) and 11-deoxoglycyrrhetic acid (11-deoxoGA), with I50 values of 2-4 x 10(-7) M. However, 18 alpha-stereoisomers (I50 = 3-7 x 10(-6) M) of GA, 3-deoxyGA and 11-deoxoGA were one tenth less inhibitory on the enzyme activity than the corresponding 18 beta-isomers. On the other hand, 18 alpha-stereoisomers of GA, 3-deoxyGA and 11-deoxoGA inhibited 3 alpha-hydroxysteroid dehydrogenase activity of rat liver cytosol more potently than the corresponding 18 beta-isomers. I50 values of 18 alpha- and 18 beta-isomers were 2 and 7 x 10(-6) M, respectively, in the case of GA, 8 and 20 x 10(-6) M in 3-deoxyGA, 3 and 20 x 10(-6) M in 11-deoxoGA. These results indicate that the 18 beta-conformation of oleanane is important for the inhibition of 11 beta-hydroxysteroid dehydrogenase but on the contrary the 18 alpha-conformation is important for the inhibition of 3 alpha-hydroxysteroid dehydrogenase.     

Silica sol-gel/organic hybrid material for protein encapsulated column of capillary electrochromatography

A new-type of sol-gel/organic hybrid composite material using gelatin or chitosan with tetramethoxysilane was developed for the bovine serum albumin (BSA)-encapsulated monolithic column for capillary electrochromatography (CEC). The composite monolith was used to immobilize BSA in a fused-silica capillary. The addition of gelatin and chitosan to the alkoxysilane enabled the enantioseparation of Trp. A very small amount of these polymers were effective for the enantioseparation. Especially, the monolithic column prepared from chitosan with tetramethoxysilane showed a high enantioselectivity for Trp enantiomers and the value (alpha' = t2/t1, t1: fast eluted enantiomer, t2: second eluted enantiomer) reached 1.15 on CEC mode. Furthermore, the composite materials exhibited a higher stability compared to the silica sol-gel column. These results showed that the sol-gel/organic hybrid composite was useful as a monolithic matrix for the BSA-encapsulated column for CEC.     

Palladium(0)-catalyzed stereoselective cyclization of allenenes: divergent synthesis of pyrrolidines and 3-azabicyclo[3.1.0]hexanes from single allenenes

Two novel palladium(0)-catalyzed cyclizations of allenenes are described. Treatment of allenenes such as N-(1-alkyl-2,3-butadienyl)-N-allylsulfonamide with an aryl halide and K(2)CO(3) in the presence of a catalytic amount of Pd(PPh(3))(4) in dioxane affords 2,3-cis-pyrrolidines in a stereoselective manner. In sharp contrast, cyclization of the same allenenes using catalytic Pd(2)(dba)(3) x CHCl(3) in the presence of allyl methyl carbonate in CH(3)CN leads to stereoselective formation of a 3-azabicyclo[3.1.0]hexane framework in moderate yields.     

Convergent synthesis of polycyclic ethers via the intramolecular allylation of alpha-acetoxy ethers and subsequent ring-closing metathesis

The Lewis acid mediated reaction of alpha-acetoxy ethers 15-22 gave the corresponding cyclized products 23, 25, 27, 29, 31, 32, 34, and 36 in good yields with high stereoselectivities. Those cyclized products were subjected to ring-closing metathesis to afford the polycyclic ethers 38-42, 44, and 45 in good yields. The usefulness of the present methodology was demonstrated by the convergent synthesis of the CDEF ring system of brevetoxin B (1) and the CDEFG ring system of gambierol (2).     

The Biological Effects of Forsythia Leaves Containing the Cyclic AMP Phosphodiesterase 4 Inhibitor Phillyrin

Forsythia fruit (Forsythia suspensa Vahl (Oleaceae)) is a common component of Kampo medicines for treating the common cold, influenza, and allergies. The main polyphenolic compounds in the leaves of F. suspensa are pinoresinol β-d-glucoside, phillyrin and forsythiaside, and their levels are higher in the leaves of the plant than in the fruit. It is known that polyphenolic compounds stimulate lipid catabolism in the liver and suppress dyslipidemia, thereby attenuating diet-induced obesity and polyphenolic anti-oxidants might attenuate obesity in animals consuming high-fat diets. Recently, phillyrin was reported as a novel cyclic AMP phosphodiesterase 4 (PDE4) inhibitor derived from forsythia fruit. It was expected that the leaves of F. suspensa might display anti-obesity effects and serve as a health food material. In this review, we summarized our studies on the biological effects of forsythia leaves containing phillyrin and other polyphenolic compounds, particularly against obesity, atopic dermatitis, and influenza A virus infection, and its potential as a phytoestrogen.