Enantioselective synthesis of β-hydroxyisobutyric acid: a useful synthon in the synthesis of polypropionate-type natural products

The aldol reaction of formaldehyde with the dicyclopentylborinyl enolate derived from $\text{S}$-(or $\text{R}$-) 1-tert-butyldimethylsilyloxy-l-cyclohexylbutan-2-one, followed by desilylation and sodium meta-periodate oxidation, provides $\text{R}$-(or $\text{S}$-) β-hydroxyisobutyric acid.     

Imprinting modulates processing of visual information in the visual wulst of chicks

Background

Results of the Women's Health Initiative Memory Study (WHIMS) raised concerns regarding the timing and formulation of hormone interventions. Conjugated equine estrogens (CEE), used as the estrogen therapy in the WHIMS trial, is a complex formulation containing multiple estrogens, including several not secreted by human ovaries, as well as other biologically active steroids. Although the full spectrum of estrogenic components present in CEE has not yet been resolved, 10 estrogens have been identified. In the present study, we sought to determine which estrogenic components, at concentrations commensurate with their plasma levels achieved following a single oral dose of 0.625 mg CEE (the dose used in the WHIMS trial) in women, are neuroprotective and whether combinations of those neuroprotective estrogens provide added benefit. Further, we sought, through computer-aided modeling analyses, to investigate the potential correlation of the molecular mechanisms that conferred estrogen neuroprotection with estrogen interactions with the estrogen receptor (ER).

Results

Cultured basal forebrain neurons were exposed to either β-amyloid_25–35 or excitotoxic glutamate with or without pretreatment with estrogens followed by neuroprotection analyses. Three indicators of neuroprotection that rely on different aspects of neuronal damage and viability, LDH release, intracellular ATP level and MTT formazan formation, were used to assess neuroprotective efficacy. Results of these analyses indicate that the estrogens, 17α-estradiol, 17β-estradiol, equilin, 17α-dihydroequilin, equilinen, 17α-dihydroequilenin, 17β-dihydroequilenin, and Δ^8,9-dehydroestrone were each significantly neuroprotective in reducing neuronal plasma membrane damage induced by glutamate excitotoxicity. Of these estrogens, 17β-estradiol and Δ^8,9-dehydroestrone were effective in protecting neurons against β-amyloid_25–35-induced intracellular ATP decline. Coadministration of two out of three neuroprotective estrogens, 17β-estradiol, equilin and Δ^8,9-dehydroestrone, exerted greater neuroprotective efficacy than individual estrogens. Computer-aided analyses to determine structure/function relationships between the estrogenic structures and their neuroprotective activity revealed that the predicted intermolecular interactions of estrogen analogues with ER correlate to their overall neuroprotective efficacy.

Conclusion

The present study provides the first documentation of the neuroprotective profile of individual estrogens contained within the complex formulation of CEE at concentrations commensurate with their plasma levels achieved after an oral administration of 0.625 mg CEE in women. Our analyses demonstrate that select estrogens within the complex formulation of CEE contribute to its neuroprotective efficacy. Moreover, our data predict that the magnitude of neuroprotection induced by individual estrogens at relatively low concentrations may be clinically undetectable and ineffective, whereas, a combination of select neuroprotective estrogens could provide an increased and clinically meaningful efficacy. More importantly, these data suggest a strategy for determining neurological efficacy and rational design and development of a composition of estrogen therapy to alleviate climacteric symptoms, promote neurological health, and prevent age-related neurodegeneration, such as AD, in postmenopausal women.     

Laser induced fluorescence spectroscopy of tetracene with large Ar, Ne, and H2 clusters in superfluid He nanodroplets

Clusters of tetracene molecules with different numbers of attached (Ar)(N), (Ne)(N) and (H(2))(N) particles (N = 1-2000) are assembled inside superfluid He nanodroplets and studied via laser-induced fluorescence. The frequency shift of the fluorescence spectrum of the tetracene molecules is studied as a function of cluster size and pickup order of tetracene and cluster species. For (Ar)(N) and (Ne)(N) clusters, our results indicate that the tetracene molecules reside inside the clusters when tetracene is captured by the He nanodroplet before the cluster species; conversely, the tetracene molecules stay on the surface of the clusters when tetracene is captured after the cluster species. In the case of (H(2))(N) clusters, however, tetracene molecules reside inside the (H(2))(N) clusters irrespective of the pickup order. We conclude that (Ar)(N) and (Ne)(N) clusters are rigid at T = 0.38 K, while (H(2))(N) clusters of up to N = 2000 remain fluxional at the same temperature. The results may also indicate the occurrence of heterogeneous nucleation of the (H(2))(N) clusters, which is induced by the interaction with tetracene chromophore molecules.     

Unique inclusion properties of crystalline powder p-tert-butylthiacalix[4]arene toward alcohols and carboxylic acids

Powdery crystals of p-tert-butylthiacalix[4]arene (2) selectively include EtOH from 1:1 mixtures of MeOH-EtOH and EtOH-PrOH, and EtCO(2)H from HCO(2)H-EtCO(2)H. On the other hand, no acid is included from HCO(2)H-MeCO(2)H, even though MeCO(2)H is included from the neat acid. The origins of these phenomena are discussed based on X-ray analysis of inclusion crystals prepared separately by crystallization.     

A large thermal hysteresis loop produced by a charge-transfer phase transition in a rubidium manganese hexacyanoferrate

In a rubidium manganese hexacyanoferrate, RbMn[Fe(CN)(6)], the magnetic susceptibility (chi(M)) decreased at 225 K (=T(1/2)decreasing) and abruptly increased at 300 K (=T(1/2)increasing) in the cooling and warming processes, respectively. X-ray photoelectron spectroscopy and infrared spectroscopy indicated that the high-temperature (HT) and low-temperature (LT) phases were composed of Mn(II)-NC-Fe(III) and Mn(III)-NC-Fe(II), respectively. A structural change from cubic (F43m, a = 10.533 A) to tetragonal (I4m2, a = b = 7.090 A, c = 10.520 A) accompanied the phase transition, and, on the basis of these results, the HT and LT phases were assigned to Mn(II)(t(2g)(3)e(g)(2), (6)A(1g); S = (5)/(2))-NC-Fe(III) (t(2g)(5), (2)T(2g); S = (1)/(2)) and Mn(III)(e(g)(2)b(2g)(1)a(1g)(1), (5)B(1g); S = 2)-NC-Fe(II) (b(2g)(2)e(g)(4), (1)A(1g); S = 0), respectively. This phenomenon is caused by a metal-to-metal charge transfer from Mn(II) to Fe(III) and a Jahn-Teller distortion of the produced Mn(III) ion. The reaction mechanism is discussed, considering the entropy difference between the HT and LT phases.     

A theory of adsorption kinetics with time delay and its application to overshoot and oscillation in the surface tension of gelatin solution

A theory of adsorption kinetics with time delay [Ohshima et al. (1992) Colloid Polym. Sci. 270:707] is developed and applied to the surface tension of a polymer solution. It is found that the general appearance of the overshoot and oscillation in the time course of the surface tension of aqueous gelatin solution observed by Sato and Ueberreiter [(1979) Makromol. Chem. 180:829, 1107; (1979) Polym. Prepr. Am. Chem. Soc. Div. Polym. Chem. 20:907) can be explained by the present theory.     

Separation of stereoisomers of some terpene derivatives by capillary gas chromatography-mass spectrometry and high-performance liquid chromatography using beta-cyclodextrin derivative columns

Gas chromatographic separations of the stereoisomers of menthol derivatives, important intermediates in the synthesis of physiologically active natural products, were carried out on several substituted beta-cyclodextrin (CD) columns, including per-O-methyl-beta-cyclodextrin (PME-beta-CD), heptakis(2,3-di-O-acetyl-6-tert-butyldimethylsilyl)-beta-CD (DIAC-6-TBDS-beta-CD), and heptakis(2,3-di-O-methyl-6-tert-butyldimethylsilyl)-beta-CD (DIME-6-TBDS-beta-CD) as chiral stationary phases (CSPs). With the DIME-6-TBDS-beta-CD column, a separation of the Z- and E-isomers of methylidenementhol was accomplished; no separation was achieved with the other columns. The stereoisomers of methylidenementhol and the corresponding tert-butyldimethylsilyl (TBS) ether were separated on both the beta-CD and the heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin (TME-beta-CD) columns by high-performance liquid chromatography (HPLC) with a mobile phase involving acetonitrile and H(2)O. For the separation of the Z- and E-isomers of methylidenementhol, the TME-beta-CD column was superior. In contrast, the beta-CD column was preferable in the case of the corresponding TBS ether.     

Thalidomide as a nitric oxide synthase inhibitor and its structural development

Thalidomide has been found to exhibit weak nitric oxide synthase (NOS)-inhibitory activity. Structural development studies of thalidomide showed that some N-2,6-dimethylphenylhomophthalimide analogs possess NOS-inhibiting activity.     

Highly Pure Synthesis,Spectral Assignments,and Two‐Photon Properties of Cruciform Porphyrin Pentamers Fused with Benzene Units

Tetrameric porphyrin formation of 2‐hydroxymethylpyrrole fused with porphyrins through a bicyclo[2.2.2]octadiene unit gave bicyclo[2.2.2]octadiene‐fused porphyrin pentamers. Thermal conversion of the pentamers gave fully π‐conjugated cruciform porphyrin pentamers fused with benzene units in quantitative yields. UV/Vis spectra of fully π‐conjugated porphyrin pentamers showed one very strong Q absorption and were quite different from those of usual porphyrins. From TD‐DFT calculations, the HOMO level is 0.49 eV higher than the HOMO?1 level. The LUMO and LUMO+1 levels are very close and are lower by more than 0.27 eV than those of other unoccupied MOs. The strong Q absorption was interpreted as two mutually orthogonal single‐electron transitions (683 nm: 86 %, HOMO→LUMO; 680 nm: 86 %, HOMO→LUMO+1). The two‐photon absorption (TPA) cross section value (σ⁽²⁾) of the benzene‐fused porphyrin pentamer was estimated to be 3900 GM at 1500 nm, which is strongly correlated with a cruciform molecular structure with multidirectional π‐conjugation pathways.