Conformationally Restricted Analogs of Platelet-Activating Factor (PAF)

The synthesis of the five-membered cyclic phosphorodiamidic-acid derivatives 10 and 11 as well as the preparation of the six-membered cyclic phosphates 18, 19, 22–25 , and phosphoramidates 27–32 is described. The effects of these conformationally restricted platelet-activating factor analogs on rabbit platelet aggregation are briefly discussed. The 2-oxo-1,3,2-dioxaphosphorinanes 19, 25 , and 30 were found to be equally potent platelet-activating factor antagonists as the known thiazolium salt 33 .     

Synthesis of Conformationally Constrained d-Glu-meso-DAP Analogs as Innate Immune Agonists

The dipeptide d-Glu-meso-DAP (iE-DAP) is the minimal structural fragment capable of activating the innate immune receptor nucleotide-binding oligomerization domain protein (NOD1). The meso-diaminopimelic acid (meso-DAP) moiety is known to be very stringent in terms of the allowed structural modifications which still retain the NOD1 activity. The aim of our study was to further explore the chemical space around the meso-DAP portion and provide a deeper understanding of the structural features required for NOD1 agonism. In order to achieve the rigidization of the terminal amine functionality of meso-DAP, isoxazoline and pyridine heterocycles were introduced into its side-chain. Further, we incorporated the obtained meso-DAP mimetics into the structure of iE-DAP. Collectively, nine innovative iE-DAP derivatives additionally equipped with lauroyl or didodecyl moieties at the α-amino group of d-Glu have been prepared and examined for their NOD1 activating capacity. Overall, the results obtained indicate that constraining the terminal amino group of meso-DAP abrogates the compounds’ ability to activate NOD1, since only compound 6b retained noteworthy NOD1 agonistic activity, and underpin the stringent nature of this amino acid with regard to the allowed structural modifications.     

Enantioselective Synthesis of 2‐(2‐Arylcyclopropyl)glycines: Conformationally Restricted Homophenylalanine Analogs

Starting from simple aromatic aldehydes and acetylfuran, (E)‐1‐(furan‐2‐yl)‐3‐arylprop‐2‐en‐1‐ones ( 2 ) were synthesized in high yields. Cyclopropanation of the C?C bond with trimethylsulfoxonium iodide (Me₃SO⁺I^?) furnished (furan‐2‐yl)(2‐arylcyclopropyl)methanones 3 in 90–97% yields. Selective conversion of cyclopropyl ketones to their (E)‐ and (Z)‐oxime ethers 5 and oxazaborolidine‐catalyzed stereoselective reduction of the C?N bond followed by separation of the formed diastereoisomers, furnished (2‐arylcyclopropyl)(furan‐2‐yl)methanamines 6 in optically pure form and high yield. Oxidation of the furan ring of (S,S,S)‐, (S,R,R)‐, (R,S,S)‐, and (R,R,R)‐ 6a afforded the four stereoisomers of α‐(2‐phenylcyclopropyl) glycine ( 1a ).     

Conformationally asymmetric block copolymers

The standard parameters controlling AB diblock copolymer phase behavior are χN and f_A, where χ is an A-B segment interaction parameter, N is the overall degree of polymerization, and f_A is the volume fraction of the A block. Recently, it has been recognized that the ratio of the A and B statistical segment lengths α_A/α_B also represents another important parameter. Here, we theoretically examine the effects of this latter parameter on the phase behavior using the standard Gaussian chain model. Calculations are performed using both self-consistent field theory (SCFT) and strong segregation theory (SST). The ratio α_A/α_B is shown to have strong effects on order-order phase boundaries. Furthermore, it significantly affects the relative stability of the complex phases. In particular, it enhances the metastability of the perforated lamellar phase and may actually cause it to become an equilibrium structure. We also illustrate that varying α_A/α_B produces large changes in the relative domain spacings at order-order phase boundaries, which could strongly affect the kinetics of these transitions. © 1997 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 35 : 945–952, 1997     

Carnitine in Pregnancy

Summary. By the 12^th week of gestation, mean whole blood and plasma carnitine levels are already significantly (p<0.01) lower than those of controls, with a further significant (p<0.01) decrease up to parturition. Diminished carnitine levels may cause a downregulation of carnitine palmitoyltransferase1 (CPT1), both the liver isoform (CPT1A) and muscle isoform (CPT1B), carnitine palmitoyltransferase2 (CPT2), and carnitine acetyltransferase (CRAT) in white blood cells of pregnant women, as determined by real time PCR using the LightCyclerSYBR Green technology.L-Carnitine-L-tartrate supplementation of 2 g/d resulted in an up to 10-fold increase of the relative mRNA abundances of CPT1B, CPT2, and OCTN2 and a 5-fold increase of CPT1A, and CRAT.There is a relationship between the relative mRNA levels of CPT1A and CPT1B and the FFA plasma levels. The substitution of 2 g L-carnitine-L-tartrate/d resulted in significant (p<0.001) lower FFA levels compared to untreated controls and the groups substituted with 0.5 and 1 g L-carnitine/d although plasma carnitine levels were not significantly increased. The most substantial effect was the reduced portion of acylcarnitines on total carnitine in those women receiving 2 g L-carnitine-L-tartrate.Carnitine substitution resulted in an enhanced excretion of both, free carnitine and acylcarnitines, whereas acetylcarnitine accounts for 50–65% of total acylcarnitines.The results of the present study provide evidence that L-carnitine supplementation in pregnancy in sufficient doses avoids a striking increase of plasma FFAs, which are thought to be the main cause of insulin resistance and consequently gestational diabetes mellitus (GDM).     

Conformational Transformations of Some Cyclohexyl Esters

The ring inversion and internal rotation parameters in cyclohexylformate, cyclohexylacetate, cyclo- hexylbutyrate, and cyclohexylvalerate molecules were studied by the MM2 method using the force field. The entropy of gaseous cyclohexylformate at T = 283.19 K calculated by statistical thermodynamics methods agrees fairly well with the experimental value; this is indirect support of the correctness of the calculated parameters of the V ( ) functions for internal rotation and ring inversion in cyclohexylformate molecules.     

甲基环己基二氯硅烷合成工艺的研究

研究了在常压和无光照的情况下由环己烯和甲基二氯硅烷合成甲基环己基二氯硅烷的工艺，着重研究了合适的催化剂和助催化剂对氢硅加成反应的影响，并就反应液温度和反应时问对反应产物的影响进行色谱跟踪，研究显示反应过程可由反应液温度或反应时间来控制。该过程生产设备简单、操作简便、收率高。     

Carnitine in Pregnancy

By the 12^th week of gestation, mean whole blood and plasma carnitine levels are already significantly (p<0.01) lower=" than=" those=" of=" controls,=" with=" a=" further=" significant=">p<0.01) decrease=" up=" to=" parturition.=" diminished=" carnitine=" levels=" may=" cause=" a=" downregulation=" of=" carnitine=" palmitoyltransferase1=" (cpt1),=" both=" the=" liver=" isoform=" (cpt1a)=" and=" muscle=" isoform=" (cpt1b),=" carnitine=" palmitoyltransferase2=" (cpt2),=" and=" carnitine=" acetyltransferase=" (crat)=" in=" white=" blood=" cells=" of=" pregnant=" women,=" as=" determined=" by=" real=" time=" pcr=" using=" the=" lightcyclersybr=" green=">L-Carnitine-L-tartrate supplementation of 2 g/d resulted in an up to 10-fold increase of the relative mRNA abundances of CPT1B, CPT2, and OCTN2 and a 5-fold increase of CPT1A, and CRAT.     

α-萘基环己基甲基酮仿生合成新方法

α-萘基环己基甲基酮仿生合成新方法;四氢叶酸辅酶;苯并咪唑甲基碘盐;Grignard试剂;α-萘基环己基甲基酮;仿生合成     

A Conformationally Stable Contorted Hexabenzoovalene

Contorted two‐dimensional aromatic molecules are fascinating synthetic targets because they are molecular “cutouts” of nonplanar graphene structures, fullerenes, or carbon nanotubes. In most cases, the curvature is introduced by the implementation of either five‐, seven‐, or eight‐membered rings into the fused aromatic plane. Curvature can also be generated for two‐dimensional systems consisting of six‐membered rings exclusively, by the introduction of cove or fjord regions. The synthesis of a polycyclic aromatic hydrocarbon (PAH) that contains two peripheral triptycene units and six tert‐butyl substituents is described. As a result of steric repulsion, the structure is highly contorted with two phenylene blades of the peripheral triptycene units oriented almost coplanar with respect to each other at a distance of 16 Å, as has been verified by single crystal X‐ray diffraction. The conformation is stable in solution even at a temperature of 150 °C. Additionally, internal tert‐butyl groups could be selectively removed, allowing a UV/Vis‐spectroscopic comparison of two structures with the same π‐system, but different degrees of contortion.     

硫酸氢钠催化合成羧酸环己酯

硫酸氢钠能够代替硫酸作为酯化作用的催化剂。研究了一水硫酸氢钠催化合成丙酸环己酯的反应条件。当 mol羧酸 ∶mol环己醇 ∶ mol硫酸氢钠 =2 .3∶ 1∶ 0 .0 7,以环己烷为溶剂 ,合成了甲酸环己酯、乙酸环己酯、丙酸环己酯和丁酸环己酯 ,收率为 77.9%～ 89.0 %     

Conformationally locked calixarene-based histone deacetylase inhibitors

Alkyl- and arylamidocalix[4]arene derivatives 1-11 have been designed and theoretically evaluated by docking studies as potential histone deacetylase inhibitors (HDACi). On the basis of the trimodal distribution of the calculated inhibition constants (K(i)), five alkyl- or arylamido derivatives (3, 7, 8, 9, and 11) were synthesized and tested. A qualitative accordance between the experimental results and the theoretical predictions was obtained, confirming that appropriately substituted arylamidocalix[4]arenes are active HDACi.     

Conformationally Rigid Hosts Containing Phosphonic Units

We present here a new class of cleft-like receptor molecules containing two or four phosphonates anions, tailored for multipoint binding of their substrates. Depending on the accessibility of the cleft, these hosts are water soluble and selective for short or long f , y -diammonium compounds. Due to their inherent chirality, we found that only those host-guest combinations which allow a three-point-interaction were effective.     

Unusual Reactivity of Sodium Tetramesityltetraphosphanediide towards Cyclohexyl Isocyanide

The reaction of [Na₂(thf)₄(P₄Mes₄)] (Mes=2,4,6‐Me₃C₆H₂) with cyclohexyl isocyanide (2:5) resulted in the formation of the heterocyclic N‐(tetramesityltetraphosphacyclopentylidene)cyclohexylamine [cyclo‐{P₄Mes₄C(NCy)}] ( 2 ) (30–35 %), the unusual 1,3,5‐triphospha‐1,4‐pentadiene ( 3 ) (40–45 %), and small amounts of the dimeric iminomethylidenephosphane cyclo‐{PMesC(NCy)}₂ ( 4 ). With catalytic amounts of AgBF₄, 2 was the major product. The reaction of 2 with [CuBr(SMe₂)] (1:1) produced bromido‐bridged dimeric Cu^I complex 5 . Molecular structures of compounds 3 , 4 , and 5 were obtained.     

Plant-Based Seafood Analogs

There is a growing global need to shift from animal- towards plant-based diets. The main motivations are environmental/sustainability-, human health- and animal welfare concerns. The aim is to replace traditional animal-based food with various alternatives, predominantly plant-based analogs. The elevated consumption of fish and seafood, leads to negative impacts on the ecosystem, due to dwindling biodiversity, environmental damage and fish diseases related to large-scale marine farming, and increased intake of toxic substances, particularly heavy metals, which accumulate in fish due to water pollution. While these facts lead to increased awareness and rising dietary shifts towards vegetarian and vegan lifestyles, still the majority of seafood consumers seek traditional products. This encourages the development of plant-based analogs for fish and seafood, mimicking the texture and sensorial properties of fish-meat, seafood, or processed fish products. Mimicking the internal structure and texture of fish or seafood requires simulating their nanometric fibrous-gel structure. Common techniques of structuring plant-based proteins into such textures include hydrospinning, electrospinning, extrusion, and 3D printing. The conditions required in each technique, the physicochemical and functional properties of the proteins, along with the use of other non-protein functional ingredients are reviewed. Trends and possible future developments are discussed.     

Conformationally controlled intramolecular charge transfer complexes

Trans-1-acceptor-2-donor-substituted cyclohexanes (1), as well as their 4- (or 5-)methyl-substituted homologues (2), have been prepared and are shown to form intramolecular charge-transfer (donor-acceptor) complexes. These weak complexes are turned on and off by the chair-chair interconversion of the cyclohexane ring. The CT absorptions have been measured and the equilibrium constants for the ring reversal have been determined by UV/vis spectroscopy at 298 K, as well as by NMR spectroscopy at two temperatures: at 183 K, by direct comparison of signals due to the two chair conformations, and at 300 K, by comparison of calculated and measured widths of the alpha-proton signals. The Gibbs free energies assigned to the donor-acceptor interactions range between 0 and -1 kcal mol(-1). A crystal structure of one of the complexes (1b) confirms the intramolecular donor-acceptor alignment and interaction. The regioisomers of the methyl-substituted complexes were characterized by NOE interaction between the methyl and an alpha-proton cis to it.     

Bromine-Promoted Glycosidation of Conformationally Superarmed Thioglycosides

Presented herein is a study of the conformation and reactivity of highly reactive thioglycoside donors. The structural studies have been conducted using NMR spectroscopy and computational methods. The reactivity of these donors has been investigated in bromine-promoted glycosylations of aliphatic and sugar alcohols. Swift reaction times, high yields, and respectable 1,2-cis stereoselectivity were observed in a majority of these glycosylations.