Solanum-alkaloide—Cl : Absolute konfiguration 23-hydroxylierter 22,26-epimino-cholestane an C-22 und C-23

According to X-ray analysis of(22S:23R:25S)-22,26-epimino-5α-cholestane-3β,16β,23-triolhydrobromide (4-HBr) the assignment of the absolute configuration of the 23-hydroxylated 22,26-epimino-cholestanes 4 and 5 has been corrected.     

Conversion of spirostane and solanidane into pregnane (1)introduction of oxygen function into C-23

A spirosolane derivative possessing a hydroxyl group at C-23, esculeogenin A, a sapogenol of tomato saponin, was found to be easily converted into the corresponding pregnane derivative by refluxing with aqueous pyridine. Therefore, introduction of a hydroxyl group into the C-23 of diosgenin (as representative of spirostane derivatives) and solasodine (as representative of spirosolane derivatives) was attempted by the reaction of NaNO(2)-BF(3)?·?Et(2)O. In diosgenin, the objective compound was obtained by the reaction in AcOH. However, in solasodine, we obtained a 23-nitroso derivative by the reaction in AcOH and 23,24-bisnorcholanic acid 22-16 lactone, or vespertilin, in AcOH and CHCl(3).     

Hydrogen atom transfer methodology for the synthesis of C-22, C-23, and C-25 stereoisomers of cephalostatin north 1 side chain from spirostan sapogenins

A simple synthesis of all eight C-22, C-23, and C-25 diastereoisomers of the cephalostatin north 1 side chain has been accomplished from (25R)-5α-spirostan-3β-ol (tigogenin). The synthesis involves selective hydroxylations at C-23 and C-25 and reductive opening of the 1,6-dioxaspiro[4.5]decane spirostan system to give a conveniently protected 5α-furostan-3β,23,25,26-tetrol. The construction of the required 1,6-dioxaspiro[4.4]nonane system entailed an intramolecular hydrogen abstraction reaction promoted by the C-25 alkoxyl radical as the key step. Acid-catalyzed isomerization of the spiroketal unit suggested that 22R isomers are the thermodynamic products while the 22S isomers are the result of kinetic control. The acid-catalyzed equilibrium between 1,6-dioxaspiro[4.4]nonane and 1,6-dioxaspiro[4.5]decane systems was also studied. In the 1,6-dioxaspiro[4.4]nonane units, the observed ³J_23,24 coupling constants suggest that the five-membered puckered ring-F undergoes substantial conformational changes on going from 22S to 22R isomers.     

One-step axial acetoxylation at C-23. A new method for the functionalization of the side chain of steroid sapogenins

Treatment of steroid sapogenins with diacetoxyiodobenzene (DIB) and boron trifluoride ethyl etherate in acetic acid led to the introduction of an axial acetoxyl group at position C-23 of the side chain.     

Synthesis and biological activity of 23-hydroxybetulinic Acid C-28 ester derivatives as antitumor agent candidates

23-Hydroxybetulinic acid (1) served as the precursor for the synthesis of C-28 ester derivatives. The target compounds were evaluated in vitro for their antitumor activities against five cell lines (A549, BEL-7402, SF-763, B16 and HL-60). Among the obtained compounds, 6i had the most potent antitumor activity, with the IC₅₀ values of 8.35 μM in HL-60 cells and showed similar antitumor activity as cyclophosphamide in H22 liver tumor and as 5-fluorouracil in B16 melanoma in vivo.     

An efficient synthesis of the C-23 deoxy, 17 alpha-hydroxy South 1 hemisphere and its cephalostatin 1 analog

[reaction: see text] Methods for functionalization of the D ring of diene 1 were investigated. This study led to efficient syntheses of 3 and the subsequent 23'-deoxy,17'alpha-hydroxy cephalostatin 1 analog (4). The bioactivity data of 2 and 4 are in the low nanomolar range for a 10-cell-line minipanel.     

Structure of Nanobody Nb23

Background: Nanobodies, or VHHs, are derived from heavy chain-only antibodies (hcAbs) found in camelids. They overcome some of the inherent limitations of monoclonal antibodies (mAbs) and derivatives thereof, due to their smaller molecular size and higher stability, and thus present an alternative to mAbs for therapeutic use. Two nanobodies, Nb23 and Nb24, have been shown to similarly inhibit the self-aggregation of very amyloidogenic variants of β2-microglobulin. Here, the structure of Nb23 was modeled with the Chemical-Shift (CS)-Rosetta server using chemical shift assignments from nuclear magnetic resonance (NMR) spectroscopy experiments, and used as prior knowledge in PONDEROSA restrained modeling based on experimentally assessed internuclear distances. Further validation was comparatively obtained with the results of molecular dynamics trajectories calculated from the resulting best energy-minimized Nb23 conformers. Methods: 2D and 3D NMR spectroscopy experiments were carried out to determine the assignment of the backbone and side chain hydrogen, nitrogen and carbon resonances to extract chemical shifts and interproton separations for restrained modeling. Results: The solution structure of isolated Nb23 nanobody was determined. Conclusions: The structural analysis indicated that isolated Nb23 has a dynamic CDR3 loop distributed over different orientations with respect to Nb24, which could determine differences in target antigen affinity or complex lability.     

FKBP23 in ER binds to BiP specifically

FKBP23 was found in mouse endoplasmic reticulum (ER) in 1998. It consists of an N-terminal peptidyl-prolyl cis-trans isomerase (PPIase) domain and a C-terminal domain with Ca2+ binding sites. The fusion protein of mouse FKBP23 and glutathione S-transferase (GST), GST-FKBP23, and the fusion protein of BiP, a member of heat shock protein 70 (Hsp 70) in ER, and GST, GST-BiP, were subcloned in E. coli, expressed and purified. The fusion proteins were restrictively digested by Factor Xa (FaXa) to obtain the free cloned proteins FKBP23 and BiP. With the assay of adsorption of free FKBP23 or BiP with GST-BiP or GST-FKBP23 attached to the Glutathione-Sepharose 4B, the adsorbed FKBP23 or BiP could be detected by Immunoblot. It means that FKBP23 binds to BiP. Furthermore, BiP in leukocyte ER-extract can be adsorbed with GST-FKBP23 attached to the glutathione-Sepharose 4B. It shows that FKBP23 binds to natural BiP in ER, too. These experiments show that a PPIase binds to a molecular chaperone of the Hsp70 family.     

Structural revision of terpenoids with a (3Z)-2-methyl-3-penten-2-ol moiety by the synthesis of (23E)- and (23Z)-cycloart-23-ene-3beta,25-diols

Synthesis of (23E)-cycloart-23-ene-3beta,25-diol (1) and its 23Z-isomer 2 was achieved by using cycloartenol as a starting material, thus revising the proposed structure of natural 2 to 1 unequivocally. These synthetic studies revealed that the structural revision (Z-form --> E-form) should also be applied to terpenoids such as (23Z)-3beta-acetoxyeupha-7,23-diene-25-ol, (23Z)-tirucalla-7,23-diene-3beta,25-diol, quadrangularol A, quadrangularic acid K, and daurichromene C.     

第23届国际凝聚态核科学会议（ICCF-23）介绍

ICCF是凝聚态核科学研究领域最重要的系列性国际会议, ICCF-23于2021年6月9～11日在厦门大学召开,会议主席是田中群院士.共有33个国家和地区的433名代表参会,收录摘要86篇.本次会议的主要进展是多个小组在Pd(Ni)-D_2O(H_2O)电解体系和Pd(Ni)-D_2(H_2)体系中观测到超热,突破了传统上只有Pd-D和Ni-H体系才能产生超热的成见;多个小组在合金-D_2(H_2)体系中观测到稳定的十瓦级超热;两个小组证实氧化层在超热产生中起重要作用,纳米或介观尺寸样品明显好于体样品.多个小组观测到含氢体系在电解、气相和放电条件下的核嬗变并呈现出某种规律性.     

Untersuchungen an den Mischkristallreihen Y6Mn23—Y6Fe23 und YMn2—YFe2

Zusammenfassung Durch Untersuchungen an Legierungen der Zusammensetzung Y₆(Mn, Fe)₂₃ und Y(Mn, Fe)₂ wird festgestellt, daß in den pseudobinären Systemen Y₆Mn₂₃–Y₆Fe₂₃ und YMn₂–YFe₂ lückenlose Mischbarkeit besteht. Die Änderung der Gitterparameter mit der Zusammensetzung wird angegeben.

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Investigations of alloys for compositions Y₆(Mn, Fe)₂₃ and Y(Mn, Fe)₂ yield complete solid solutions of the pseudo-binary systems Y₆Mn₂₃–Y₆Fe₂₃ and YMn₂–YFe₂. The lattice parameters for various compositions are reported.

     

Metal ions-induced conformational change of P23 by using TNS as fluorescence probe

In 10 mM N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid (Hepes), pH 7.4, 25 degrees C, the conformational change of the truncated form of ciliate Euplotes Octocarinatus centrin (P23) induced by metal ions were investigated using 2-p-toluidinylnaphthalene-6-sulfonate (TNS) as a probe. The results show that upon metal ions binding, P23 undergo a conformational change and the contributions to the conformational change from the two EF-hands are different, and Tb3+ has more larger influence than Ca2+ with the same concentration metal ions, which provide possible the evidence that the different EF-hands play distinct biological functions. Meanwhile, the conditional binding constants of TNS and Ca2-loaded or Tb2-loaded P23 were obtained, K (Ca2-P23+TNS)=(7.49+/-0.88)x10(5) mol-1 L, K (Tb2-P23+TNS)=(8.24+/-0.49)x10(5) mol-1 L.     

Crystal structures and thermal and electrical properties of the new silver (poly)chalcogenide halides Ag23Te12Cl and Ag23Te12Br

Two new silver (poly)chalcogenide halides, Ag23Te12Cl and Ag23Te12Br, were characterized by powder X-ray phase analysis, energy dispersive X-ray analysis, and crystal structure determinations at various temperatures. Thermal analyses of both compounds and electrochemical measurements for the bromide completed the investigation. The compounds Ag23Te12X (X = Cl, Br) are isostructural and crystallize orthorhombically (space group Pnnm, Z = 4) as systematic twins. The lattice parameter values derived from X-ray powder data were a = 21.214(2) A, b = 21.218(2) A, c = 7.7086(7) A, and V = 3469.8(6) A (3) for Ag23Te12Cl at 293 K and a = 21.170(1) A, b = 21.170(1) A, c = 7.7458(5) A, and V = 3471.4(4) A (3) for Ag23Te12Br at 298 K. An enhanced silver ion mobility was revealed by impedance spectroscopy investigations. No phase transitions were observed in the temperature range 100-750 K. These two silver(I) (poly)chalcogenide halides are the second set of representatives of a new class of coinage-metal (poly)chalcogenide halides in which both covalently bonded [Te2](2-) dumbbells and ionically bonded Te(2-) anions appear.     

Increased lysine N-methylation of a 23-kDa protein during hepatic regeneration

The methylation of a 23-kDa nuclear protein increased after partial hepatectomy and methylation returned to basal levels after the initial stage of regeneration. The methylating enzyme was partially purified from rat liver by ammonium sulfate precipitation, DEAE-anion exchange chromatography and Butyl-Sepharose chromatography. The 23-kDa protein was purified from a nuclear fraction of liver tissue with SP-Sepharose. When the 23-kDa protein was methylated with the partially purified methyltransferase and analyzed on C(18) high performance liquid chromatography (HPLC), the methylated acceptor amino acid was monomethyl lysine (MML). Previously, only arginine N-methylation of specific substrate proteins has been reported during liver regeneration. However, in this report, we found that lysine N-methylation increased during early hepatic regeneration, suggesting that lysine N-methylation of the 23-kDa nuclear protein may play a functional role in hepatic regeneration. The methyltransferase did not methylate other proteins such as histones, hnRNPA1, or cytochrome C, suggesting the enzyme is a 23-kDa nuclear protein- specific lysine N-methyltransferase.     

Lead tetraacetate-iodine oxidation of 23-spirostanols

Reactions of 23R- and 23S-23-spirostanols in the 25R and 25S series with lead tetraacetate-iodine were studied. The reactions carried out at low temperature afforded d-seco-iododialdehydes and C₂₂ lactones, while similar reactions performed in refluxing tetrachloromethane yielded 20-chlorolactones and their 21-acetoxy derivatives irrespective of the hydroxyl group configuration at C-23. The reaction mechanisms are discussed.     

J(23)cis and J(23)trans of 2-carbonyl substituted 2,3-dihydrobenzofurans

The J(23)cis and J(23)trans values in several 2-carbonyl substituted 2,3-dihydrobenzofurans were measured. Although J(cis)>J(trans), the values found disagree with the Karplus rule.     

An assisted solvolysis of 23-spirostanyl bromides and tosylates. A new rearrangement of spirostanes to the bisfuran systems

Steroidal sapogenins bearing a good leaving group at C23 undergo a completely stereospecific rearrangement under a variety of conditions via a mechanism involving neighboring-group participation by the acetal oxygen atom in the departure of the nucleofuge from C23. The reactions of equatorial (23S)-23-bromo- or (23S)-23-tosyloxyspirostanes with either the alpha (25R) or beta (25S) oriented 25-methyl group lead to the bisfuran products with inversion of configuration at C23. The reactions of the starting compounds with axial substituents (23R) at C23 require drastic conditions and result in the formation of the corresponding olefin accompanied by the rearranged product (in the case of the 25S isomer only).     

Synthesis of 23-ketocholestane derivatives with different side-chain lengths (asterosapogenin analogs)

Syntheses were developed for 23-ketoasterosapogenin analogs with various sidechain lengths from dimethyl(tert-butyl)silyloxypregnenolone (DMTBS-pregnenolone) through 20-hydroxy-23-carboxylates or 22-acetylenic (C₅, C₆) derivatives by reduction and allylic rearrangement with concurrent oxidation of the intermediate 23-hydroxy-27-nor- and 27-nor-26-methylcholestanes.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 965–969, April, 1991.     

Glycosylation analysis of interleukin-23 receptor: elucidation of glycosylation sites and characterization of attached glycan structures

Interleukin-23 (IL-23) is a heterodimeric cytokine, a central factor in chronic/autoimmune inflammation. It signals through a heterodimeric receptor consisting of IL-23r, which is heavily glycosylated. The structural characterization of IL-23r has not been reported. In this work, glycosylation profiles of soluble recombinant human IL-23r (rhIL-23r) were established using mass spectrometry (MS), which included defining glycosylation sites, degree of glycosylation occupancy of each site and structure of attached oligosaccharides. Specifically, precursor ion scan of oxonium ion protonated N-acetylglucosamine (GlcNAc(+)) (m/z 204) was performed using a triple quadrupole MS instrument to locate the retention time of glycopeptides. Both the glycopeptides and their corresponding deglycosylated forms in each collected HPLC fraction were studied by liquid chromatography-tandem mass spectrometry (LC-MS/MS) (LTQ-Orbitrap) for glycosylation site profiling. The attached glycan structures were elucidated by collision-induced dissociation (CID) fragmentation of target glycopeptides in combination with accurate mass measurement. Eight glycosylation sites were identified on IL-23r (Asn24, Asn209, Asn239, Asn157, Asn118, Asn250, Asn58 and Asn6). Most of the glycosylation sites were > 95% occupied except Asn250 and Asn6. Those two sites were 88% and 45% occupied by estimation from trypsin digestion and were 55% and 42% occupied from LysC digestion. Multiple glycoforms were observed in IL-23r. Most of them were bi-, tri- or tetra-antennary complex type structures with fucose and sialic acid. High mannose and hybrid type glycans were only observed on Asn157. The structural characterization on IL-23r glycosylation provides useful information for better understanding of the biological function of IL-23r.