Conjugate addition of allylsilanes to α,β-unsaturated acylsilanes

α,β-Unsaturated acylsilanes serve as highly reactive carboxylic acid equivalents in conjugate allylation reactions with allylsilane derivatives.     

Synthesis and In Vivo antitumor and antiviral activities of 2′-deoxyribofuranosyl and arabinofuranosyl nucleosides of certain purine-6-sulfenamides,sulfinamides and sulfonamides

2′-Deoxyribofuranosyl and arabinofuranosyl nucleosides of certain purine-6-sulfenamides, sulfinamides and sulfonamides have been prepared by sequential amination and controlled oxidation of the corresponding 6-thiopurine nucleosides, and evaluated for antiviral and antitumor activities in mice. Amination of 2′-deoxy-6-thioinosine ( 4a ) and 9-β-D-arabinofuranosyl-6-thiopurine ( 4c ) with chloramine solution gave the corresponding 6-sulfenamides 5a and 5c , respectively, which on selective oxidation with 3-chloroperoxybenzoic acid (MCPBA) gave diastereomeric 9-(2-deoxy-β-D-erythro-pentofuranosyl)purine-6-sulfinamide ( 6a ) and 9-β-D-arabinofuranosylpurine-6-sulfinamide ( 6c ), respectively. However, oxidation of 5a and 5c with excess of MCPBA gave the corresponding 6-sulfonamide derivatives 7a and 7c , respectively. Similar amination of 2′-deoxy-6-thioguanosine ( 4b ), ara-6-thioguanine ( 4d ) and α-2′-deoxy-6-thioguanosine ( 8 ) gave the respective 6-sulfenamide derivatives 5b, 5d and 9 . Controlled oxidation of 5b, 5d and 9 gave (R,S)-2-amino-9-(2-deoxy-β-D-erythro-pentofuranosyl)purine-6-sulfinamide ( 6b ), (R,S)-2-amino-9-β-D-arabinofuranosylpurine-6-sulfinamide ( 6d ) and the α-anomer of ( 6b) (10 ), respectively. The diastereomeric mixture of (R,S )-10 was partially resolved and the structure of S -10 was assigned by single-crystal X-ray diffraction analysis. Oxidation of 5b, 5d and 9 with excess of MCPBA afforded the respective 6-sulfonamide derivatives 7b, 7d and 11 . Nucleosides 5c and 7c were significantly active against Friend leukemia virus in mice, whereas 6c was somewhat less active. Of the 20 nucleosides evaluated, 12 exhibited biologically significant anti-L1210 activity in mice. Nucleosides 6b and 7a at 173 mg/kg/day × 1 showed a T/C of 153, whereas 7d at 800 mg/kg/day × 1 showed a T/C of 153 against L1210 leukemia. The α-nucleoside 9 at 480 mg/kg/day × 1 gave a T/C of 172. A single treatment with 6b, 7a, 7d and 9 reduced the body burdens of viable L1210 cells by more than 99.2%. The antileukemic activity of these novel nucleosides tended to parallel solubility.     

Equilibrium adsorption data from temperature-programmed desorption experiments

This work describes a novel method that enables the calculation of a series of adsorption isotherms basically from a single Temperature-Programmed Desorption (TPD) experiment. The basic idea is to saturate an adsorbent packed in a fixed bed at a certain feed concentration and temperature and to subsequently increase its temperature linearly with time, while maintaining a constant feed concentration.We measured TPD response curves for carbon dioxide on activated carbon at different heating rates for various combinations of feed concentration, molar flow rate and particle size. Response curves from an axially dispersed plug flow model were fitted to experimental data by adjustment of the Langmuir parameters. Adsorption isotherms calculated with these fitted parameters are in good agreement with adsorption data obtained by other methods over the full temperature range.The influence of heating rate on intraparticle mass transfer resistance is discussed.     

Protective Effects of <Emphasis Type="Italic">L</Emphasis>-Carnitine on Myocardium of Experimentally Diabetic Rats with Additional Ischaemia and Reperfusion

Summary. We investigated the protective effects of L-carnitine against damage to the heart caused by diabetes-induced alterations and additional ischaemia and reperfusion in diabetic BB/OK rats using histological techniques, morphometry, biochemical parameters of oxidative stress, and SOD expression. The results revealed that diabetes-induced morphological changes were partly improved or nearly prevented by substitution of L-carnitine, which also seemed to improve the reduced tolerance of diabetic myocardium towards ischaemia/reperfusion with respect to morphological parameters. Immunohistochemical and biochemical parameters of oxidative stress such as SOD protein expression as well as SOD and GPx activity indicate increased free oxygen radical level in the ischaemic/reperfused diabetic myocardium, which is clearly decreased by L-carnitine treatment. We suggest that L-carnitine may be an adequate “causal” agent in the protection of myocardial alterations in diabetes with additional ischaemia and reperfusion, as it stabilizes mitochondrial and cellular function and acts through its antioxidative or radical scavenging potential. Further investigations are necessary to determine an approach towards adjuvant treatment of diabetic myocardial complications using L-carnitine.     

Synthesis of Ethyl (2RS,3SR)-1-Tosyl-3-Vinylazetidine-2-carboxylate and ethyl (2RS,E)-3-ethylidene-1-tosylazetidine-2-carboxylate (=rac-ethyl N-tosylpolyximate)

The synthesis of 3-ethylideneazetidine-2-carboxylic acid (=polyoximic acid; 3 ) is a approached in two different ways leading to potential precursors of 3 . The first way involved a ring closure to a vinyl-subsatituted azetidin. Thus, Ireland-Claisen rearrangement of the Boc-glycinates 6 and 10 of (Z)- and (E)-2-butene-1,4-diol afforded, after exchange of the N-protecting groups, the isomeric 2-(tosylamino)-3-vinylbutanolides 13 and 14 with high stereoselectivity. Only the cis-isomer 14 could be further transformed to 3-(bromomethyl)-2-(tosylamino)-4-pentenoate 17 , and in a smoth cyclization with K₂CO₃, to trans-3-vinylazetidtene-2-carboxylaze 18 (Scheme 2). In the second approach, the 3-ethylidene isomer 19 of 18 was obtained more directly by a [2+2] cycloaddition, together with the two isomers 23 and 24 , from methlallene 20 and (tosyliminno)acetate 21 (Scheme 3). The main product of this reaction was, however, 2-(tosylamino)-4-hexinoate 22 , the product of an ene reaction.     

A highly active catalyst for the reductive cyclization of ortho-nitrostyrenes under mild conditions

A mild and efficient method for the palladium-catalyzed reductive cyclization of ortho-nitrostyrenes to afford indoles is reported. Treatment of ortho-nitrostyrenes with 0.1 mol% palladium (II) trifluoroacetate [Pd(TFA)₂] and 0.7 mol% 3,4,7,8-tetramethyl-1,10-phenanthroline (tm-phen) in DMF at 15 psig CO and 80 °C afforded indoles in good to excellent yields. When the reaction was conducted in toluene, the corresponding N-hydroxyindole was isolated. A mechanism that accounts for the formation of N-hydroxyindole is proposed.     

2+2] Cycloaddition of ketenes with ynamides. A general method for the synthesis of 3-aminocyclobutenone derivatives

Ynamides react with ketenes in [2+2] cycloadditions leading to a variety of substituted 3-aminocyclobut-2-en-1-ones. The ynamides employed in these reactions are readily available via the copper-promoted N-alkynylation of carbamates and sulfonamides with alkynyl bromides and iodides. The scope of the [2+2] cycloaddition with regard to both the ketene and ynamide component is described.     

Total synthesis of quinolizidine alkaloid (-)-217A. Application of iminoacetonitrile cycloadditions in organic synthesis

[reaction: see text] An intramolecular iminoacetonitrile [4 + 2] cycloaddition functions as the key step in an efficient total synthesis of the quinolizidine alkaloid (-)-217A.     

PROPERTIES OF SYNTHETIC BACTERIORHODOPSIN PIGMENTS. FURTHER PROBES OF THE CHROMOPHORE BINDING SITE

Abstract— A series of retinals with specific structural alterations have been synthesized to probe the bacteriorhodopsin binding site. The 4-chloro-, 4-bromo- and 4-iodoretinals all form pigments with bacterioopsin but undergo an in situ displacement of the allylic halogen to form the 4-hydroxyretinal pigment. Several naphthyl retinals were prepared which effectively extend the polyene chain and/or add bulk to the ring portion of the chromophore. All the naphthyl retinals form pigments with bacterioopsin but only the pigment containing the derivative with a polyene side chain identical to that of retinal pumps protons efficiently. The 12-butyl-13-desmethylretinal was also synthesized but this analogue did not form a pigment with bacterioopsin. These results confirm the nonspecificity at the ring portion of the chromophore binding site and the importance of the role of the polyene chain in the proton pumping function of bacteriorhodopsin.     

Determination of boron in materials by cold neutron prompt gamma-ray activation analysis

An instrument for cold neutron prompt gamma-ray activation analysis (PGAA), located at the NIST Center for Neutron Research (NCNR), has proven useful for the measurement of boron in a variety of materials. Neutrons, moderated by passage through liquid hydrogen at 20 K, pass through a (58)Ni coated guide to the PGAA station in the cold neutron guide hall of the NCNR. The thermal equivalent neutron fluence rate at the sample position is 9 x 10(8) cm(-2) s(-1). Prompt gamma rays are measured by a cadmium- and lead-shielded high-purity germanium detector. The instrument has been used to measure boron mass fractions in minerals, in NIST SRM 2175 (Refractory Alloy MP-35-N) for certification of boron, and most recently in semiconductor-grade silicon. The limit of detection for boron in many materials is <10 ng g(-1).