Regioselective Dichlorination of a Non‐Activated Aliphatic Carbon Atom and Phenolic Bismethylation by a Multifunctional Fungal Flavoenzyme

The regioselective functionalization of non‐activated carbon atoms such as aliphatic halogenation is a major synthetic challenge. A novel multifunctional enzyme catalyzing the geminal dichlorination of a methyl group was discovered in Aspergillus oryzae (Koji mold), an important fungus that is widely used for Asian food fermentation. A biosynthetic pathway encoded on two different chromosomes yields mono‐ and dichlorinated polyketides (diaporthin derivatives), including the cytotoxic dichlorodiaporthin as the main product. Bioinformatic analyses and functional genetics revealed an unprecedented hybrid enzyme (AoiQ) with two functional domains, one for halogenation and one for O‐methylation. AoiQ was successfully reconstituted in vivo and in vitro, unequivocally showing that this FADH₂‐dependent enzyme is uniquely capable of the stepwise gem‐dichlorination of a non‐activated carbon atom on a freestanding substrate. Genome mining indicated that related hybrid enzymes are encoded in cryptic gene clusters in numerous ecologically relevant fungi.     

Synthesis of thermosensitive hydrogels from acryloyloxyethyl trialkyl phosphonium chloride–N‐isopropylacrylamide–N,N′‐methylenebisacrylamide terpolymers and their temperature dependence of water absorption

Thermosensitive polymer hydrogels were prepared by the copolymerization of three kinds of acryloyloxyethyl trialkyl phosphonium chlorides (AETRs) with alkyl chains of different lengths, with N‐isopropyl acrylamide (NIPAAm) and N,N′‐methylenebisacrylamide (MBAAm). The water content of the AETR–NIPAAm–MBAAm terpolymers obtained at molar ratios of the crosslinking agent greater than 2 decreased with increasing temperature and decreased sharply around 35 °C. However, the water contents of the AETR–NIPAAm–MBAAm (X/100/1) terpolymers obtained at a molar ratio of 1 of the crosslinking agent increased once with increasing temperature and then decreased from 3 to around 40 °C. The water contents of the AETR–NIPAAm–MBAAm (3/100/1 or 2) terpolymers decreased with the increasing length of alkyl chains in phosphonium groups in the terpolymers. The water contents of the AETR–NIPAAm–MBAAm terpolymers increased by the addition of a small amount of urea and then decreased with increasing urea concentration. However, the water contents decreased abruptly with the addition of NaCl. The AETR–NIPAAm–MBAAm terpolymers exhibited high adsorption for sodium dodecylbenzene sulfonate but no adsorption for sodium benzene sulfonate. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 1505–1514, 2001     

Studies on the constituents of bark of Parameria laevigata Moldenke

One new trimeric proanthocyanidin, epicatechin-(2beta-->O-->7, 4beta-->6)-epicatechin-(2beta-->O--->7, 4beta-->8)-epicatechin (5) and two new tetrameric proanthocyanidins, epicatechin-(2beta-->O-->7, 4beta-->8)-[epicatechin-(4beta-->6)]-epicatechin-(4beta-->8)-epicatechin, named as parameritannin A-1 (6), and epicatechin-(2beta-->O-->5, 4beta-->6)-[epicatechin-(2beta-->O-->7, 4beta-->8)]-epicatechin-(4beta-->8)-epicatechin, named as parameritannin A-2 (7), have been isolated from the bark of Parameria laevigata Moldenke (Apocynaceae) along with the two known dimers, proanthocyanidin A-2 (1) and proanthocyanidin A-6 (2), and two trimers, cinnamtannin B-1 (3) and aesculitannin B (4). These structures were elucidated by spectral and chemical evidence.     

The nature of the delocalized cations in azulenic bacteriorhodopsin analogs.

Depending on the size and shape of their azulenic chromophores, azulenic bacteriorhodopsin (bR) pigment analogs can exist as either an initial pigment P1, a more red-shifted final pigment P2 or an equilibrium mixture of both. The absorption spectra of red-shifted bR analogs exhibit characteristic narrow-band shapes similar to charge fully delocalized cyanine-like dyes. Therefore, all such red-shifted pigments are believed to be highly delocalized, bond-equalized carbocations. We have determined structural requirements that facilitate their formation. To describe fully the red-shift potentials of these retinal analogs, we have introduced a new parameter-percent red-shift (PRS). A large PRS value not only reflects the extent of red-shift, but is also suggestive of extensive delocalization of the positive charge. Relevance of these findings in consideration of the possibility of forming stable O-intermediates is presented. The postulated resonance hybrid-like structures for different cations of the positively charged protonated Schiff base chromophores are in fact structurally distinct species, equilibrating in response to local perturbations within the supramolecular protein environment.     

High-pressure NMR study of cis-1,n-disubstituted[n]paracyclophanes. Effect of increased pressure on the hindered internal rotation.

The effect of hydrostatic pressure on the rate of internal rotation of title compounds has been examined by the DNMR method. Quartz pressure-resisting NMR cells were used to realize the high-pressure experiments up to 390 (line shape measurements) and 450 MPa (chemical shift measurements). Application of hydrostatic pressure was found to accelerate the rotation of the benzene ring, while pressure-induced low-frequency chemical shifts of bridge methylene protons indicated that there is a considerable shrinkage of the methylene bridge structure upon pressurization.     

Internal Rotation of Ester Linkage in Phenyl Benzoate and Hydroxybenzoic Acid Dimer as Models of Aromatic Polyesters Using Density Functional Theory

The internal rotation of the ester linkage was reinvestigated more quantitatively by using the density functional theory (DFT) in order to understand the characteristic stiffness and extendedness of polymer chain found in aromatic polyesters. Phenyl benzoate ( PB ) and p‐hydroxybenzoic acid (HBA) dimer ( HB ) were selected as models of aromatic polyesters. The relaxed potential energy surface (PES) scan was carried out along the internal rotation of three bonds (denoted as R, S and T, respectively) of the aromatic esters by using the hybrid DFT (B3LYP) with 6‐31G* basis set. The rotation of S bond, which mainly determines the linearity of the molecule, leads to the trans‐ and cis‐conformers of PB . Since the cis‐conformer of PB is 7.69 kcal·mol^–1 higher than the trans‐conformer, the cis‐conformer has little population at standard condition. HB does not have the cis‐conformer. In addition, the chain persistence length of 364 Å is obtained by the rotation matrix formalism using the structural parameters of HB . These agree with the experimental understanding that poly(p‐hydroxybenzoic acid) is the class of stiff and extended polymer.     

Controlled release of DNA from zinc and magnesium ion-doped hydroxyapatites

Research on Chemical Intermediates - Hydroxyapatite (HA) is a biocompatible and porous material that is useful for gene delivery. In this study, various Zn- and Mg-doped HA samples were produced by...     

Structure-activity relationship of yohimbine and its related analogs in blocking alpha-1 and alpha-2 adrenoceptors: a comparative study of cardiovascular activities

We investigated the selectivities and structure requirements for alpha-1 and alpha-2 adrenoceptor blocking activities of yohimbine (YO) and its 12 related analogs, such as beta-yohimbine (beta-YO), dihydrocorynantheine (DHC) and (-)indoloquinolizidine ((-)IQ). The affinity of YO analogs to alpha-adrenoceptor was assessed by measuring their blockade of pressor responses to epinephrine in pithed rats. Among YO structure groups, the potency order was YO greater than DHC = beta-YO greater than geissoschizine methylether greater than 14 beta-hydroxy YO greater than 14 beta-benzoyloxy YO (inactive). (-)IQ was slightly less potent than YO, but much stronger than (+)IQ. Among (+/-)IQ structure groups, the potency order was (+/-)IQ greater than (+/-)1,12b-trans-1-hydroxy IQ much greater than (+/-)1,12b-cis-1-hydroxy IQ (inactive). (+/-)Borrerine was active, but (+/-)desmethylborrerine was inactive. The alpha-1 blocking activities of the four compounds YO, beta-YO, DHC and (-)IQ, were assessed in experiments of pressor responses to methoxamine in pithed rats and contractile responses to methoxamine in the rat vas deferens. The potency order was (-)IQ greater than YO greater than DHC greater than beta-YO. Furthermore, the alpha-2 blocking activities of the four analogs were assessed in experiments of pressor responses to clonidine and inhibition of electrically driven cardioacceleration by clonidine, in pithed rats. The potency order was YO greater than beta-YO greater than (-)IQ greater than DHC. Based on the potency ratio between alpha-1 and alpha-2 blocking activities, DHC or YO was most selective for alpha-1 or alpha-2 subtype, respectively, among the four YO analogs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Novel 1,4-dihydropyridine calcium antagonists. I. Synthesis and hypotensive activity of 4-(substituted pyridyl)-1,4-dihydropyridine derivatives

A series of 4-(substituted pyridyl)-1,4-dihydropyridine derivatives were synthesized and their hypotensive effects examined. Several compounds, 2-(N-benzyl-N-methylamino)ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitro-2-pyridyl)-3,5-pyridinedicarboxylate (2b), its 4-(4-nitro-2-pyridyl) analogue (2g), 4-(3-trifluoromethyl-2-pyridyl) analogue (2c), 4-(2-trifluoromethyl-3-pyridyl) analogue (3e), 4-(4-cyano-2-pyridyl) analogue (2e), 4-(2-cyano-3-pyridyl) analogue (3d), and 4-(6-bromo-2-pyridyl) analogue (2i), were found to have a hypotensive activity parallel to that of nicardipine; 2c and 3e, in particular, had approximately twice the duration of nicardipine, and 2e had the most potent hypotensive activity of all the derivatives synthesized.     

Coherent Array of White-Light Continuum Generated by Microlens Array

We generated a white-light continuum array by directing femtosecond laser pulses into a liquid with a microlens array. Experimental evidence demonstrates that the spatial coherence is high within a single light source in the array. We also confirmed that all the light sources in the white-light continuum array are mutually coherent. We found that the simple self-phase modulation model cannot explain this high coherence between the white continuum sources.