Thermische Lactonisierung von Estern γ-Brom-α, β-ungesättigter Carbonsäuren zu Δα-Butenoliden. Direkte γ-Bromierung von α, β-ungesättigten Säuren

By heating with iron powder at 120–150° some γ-bromo-α, β-unsaturated carboxylic methyl esters, and, less smothly, the corresponding acids, were lactonized to Δ^7alpha;-butenolides with elimination of methyl bromide. The following conversions have thus been made: methyl γ-bromocrotonate ( 1c ) and the corresponding acid ( 1d ) to Δ^α-butenolide ( 8a ), methyl γ-bromotiglate ( 3c ) and the corresponding acid ( 3d ) to α-methyl-Δ^α-butenolide ( 8b ), a mixture of methyl trans- and cis-γ-bromosenecioate ( 7c and 7e ) and a mixture of the corresponding acids ( 7d and 7f ) to β-methyl-Δ^α-butenolide ( 8c ). The procedure did not work with methyl trans-γ-bromo-Δ^α-pentenoate ( 5c ) nor with its acid ( 5d ). Most of the γ-bromo-α, β-unsaturated carboxylic esters ( 1c, 7c, 7e and 5c ) are available by direct N-bromosuccinimide bromination of the α, β-unsaturated esters 1a, 7a and 5a ; methyl γ-bromotiglate ( 3c ) is obtained from both methyl tiglate ( 3a ) and methyl angelate ( 4a ), but has to be separated from a structural isomer. The γ-bromo-α, β-unsaturated esters are shown by NMR. to have the indicated configurations which are independent of the configuration of the α, β-unsaturated esters used; the bromination always leads to the more stable configuration, usually the one with the bromine-carrying carbon anti to the carboxylic ester group; an exception is methyl γ-bromo-senecioate, for which the two isomers (cis, 7e , and trans, 7d ) have about the same stability. The N-bromosuccinimide bromination of the α,β-unsaturated carboxylic acids 1b , 3b , 4b , 5b and 7b is shown to give results entirely analogous to those with the corresponding esters. In this way γ-bromocrotonic acid ( 1 d ), γ-bromotiglic acid ( 3 d ), trans- and cis-γ-bromosenecioic acid ( 7d and 7f ) as well as trans-γ-bromo-Δ^α-pentenoic acid ( 5d ) have been prepared. Iron powder seems to catalyze the lactonization by facilitating both the elimination of methyl bromide (or, less smoothly, hydrogen bromide) and the rotation about the double bond. α-Methyl-Δ^α-butenolide ( 8b ) was converted to 1-benzyl-( 9a ), 1-cyclohexyl-( 9b ), and 1-(4′-picoly1)-3-methyl-Δ^α-pyrrolin-2-one ( 9 c ) by heating at 180° with benzylamine, cyclohexylamine, and 4-picolylamine. The butenolide 8b showed cytostatic and even cytocidal activity; in preliminary tests, no carcinogenicity was observed. Both 8b and 9c exhibited little toxicity.     

Conformations of the Ten-membered Ring in 5, 10-Secosteroids. III: (Z)-3β- and (Z)-3α-Hydroxy-5, 10-seco-1 (10)-cholesten-5-one Esters and (Z)-5, 10-seco-1 (10)-Cholestene-3, 5-dione

(Z)-3β-Acetoxy- and (Z)-3 α-acetoxy-5, 10-seco-1 (10)-cholesten-5-one ( 6a ) and ( 7a ) were synthesized by fragmentation of 3β-acetoxy-5α-cholestan-5-ol ( 1 ) and 3α-acetoxy-5β-cholestan-5-ol ( 2 ), respectively, using in both cases the hypoiodite reaction (the lead tetraacetate/iodine version). The 3β-acetate 6a was further transformed, via the 3β-alcohol 6d to the corresponding (Z)-3β-p-bromobenzoate ester 6b and to (Z)-5, 10-seco-1 (10)-cholestene-3, 5-dione ( 8 ) (also obtainable from the 3α-acetate 7a ). The ¹H-and ¹³C-NMR. spectra showed that the (Z)-unsaturated 10-membered ring in all three compounds ( 6a , 7a and 8 ) exists in toluene, in only one conformation of type C ₁, the same as that of the (Z)-3β-p-bromobenzoate 6b in the solid state found by X-ray analysis. The unfavourable relative spatial factors (interdistance and mutual orientation) of the active centres in conformations of type C ₁ are responsible for the absence of intramolecular cyclizations in the (Z)-ketoesters 6 and 7 ( a and c ).     

Tordanone,un stéroïde replié avec une jonction de cycle A/B β-cis (5β) et B/C α-cis(8α)

Tordanone, a Twice Bent Steroid Structure with Ring A/B β-cis(5β)- and Ring B/C α-cis(8α)-Fused The 3β, 14α, 25-trihydroxy-5β, 8α-cholestan-6-one ( = tordanone; 4 ) has been prepared by stereospecific hydrogenation of 3β, 14α, 25-trihydroxy-5β-cholesta-7,22ξ-dien-6-one ( 5 ). This is the first stereospecific synthesis of a B/C cis-fused steroid belonging to the 5β, 8α -cholestane group with a H-atom at positions 5β (A/B cis-fused) and 8α. The resulting twice bent structure shows a particularly strong steric hindrance of the β-face where CH₃(18) at the C/D ring junction and H_β? C(7) of the B ring are very close to each other. Structural features and mechanistic aspects of the hydrogenation are discussed.     

Correlations between chemical structure and k-value in the TLC of epimeric 3-ethinyl-3-cholestanoles

The chromatographic behaviour of TLC on silica gel of 3 pairs of epimeric 3-ethinyl-3-cholestanoles is described. It is found that the k-values of this class of compounds are predominantly influenced by the stereochemical orientation of the hydroxyl group. 3-Ethinyl-3-cholestanoles with β-configuration of the hydroxyl group have larger k-values than their α-oriented epimers.     

Stereoselective synthesis of pyrrolo[2,3-d]pyrimidine α- and β-D-ribonucleosides from anomerically pure D-ribofuranosyl chlorides: Solid-Liquid Phase-Transfer Glycosylation and 15N-NMR Spectra

Solid-liquid phase-transfer glycosylation (KOH, tris[2-(2-methoxyethoxy)ethye]amine ( = TDA-1), MeCN) of pyrrolo[2,3-d]pyrimidines such as 3a and 3b with an equimolar amount of 5-O-[(1,1 -dimethylethyl)dimethylsilyl]-2,3-O-(1-methylethylidene)-α-D -ribofuranosyl chloride (1) [6] gave the protected β-D -nucleosides 4a and 4b , respectively, stereoselectively (Scheme). The β-D -anomer 2 [6] yielded the corresponding α-D -nucleosides 5a and 5b with traces of the β-D -compounds. The 6-substituted 7-deazapurine nucleosides 6a , 7a , and 8 were converted into tubercidin (10) or its α-D -anomer (11) . Spin-lattice relaxation measurements of anomeric ribonucleosides revealed that T₁ values of H? C(8) in the α-D -series are significantly increased compared to H? C(8) in the β-D -series while the opposite is true for T₁ of H? C(1′). ¹⁵N-NMR data of 6-substituted 7-deazapurine D -ribofuranosides were assigned and compared with those of 2′-deoxy compounds. Furthermore, it was shown that 7-deaza-2′deoxyadenosine ( = 2′-deoxytubercidin; 12 ) is protonated at N(1), whereas the protonation site of 7-deaza-2′-deoxyguanosine ( 20 ) is N(3).     

Cyclodextrin chemistry. Selective modification of all primary hydroxyl groups of α- and β-cyclodextrins

Two efficient methods are described for the selective modification of all six primary hydroxyl groups of α-cyclodextrin (α-CD, 1 1 ). One, using an indirect strategy, involves protection of all 18 hydroxyl functions as benzoate esters, followed by selective deprotection of the six primary alcohol groups. The other, using a direct strategy, involves selective activation of the primary hydroxyl groups via a bulky triphenylphosphonium salt, which is then substituted by azide anion as the reaction proceeds. A number of modified α-cyclodextrin derivatives have been prepared and fully characterized, among which are: the useful intermediate α-cyclodextrin-dodeca (2, 3) benzoate ( 3 ); hexakis (6-amino-6-deoxy)-α-cyclodextrin hexahydrochloride ( 7 ); hexakis (6-amino-6-deoxy)-dodeca (2, 3)-O-methyl-α-cyclodextrin hexahydrochloride ( 9 ), hexa (6)-O-methyl-α-cyclodextrin ( 13 ). The direct substitution is shown to be even more efficient for β-cyclodextrin ( 16 ), giving the heptakis (6-azido-6-deoxy)-β-CD-tetradeca (2, 3)acetate ( 17 ), while the indirect strategy fails. The compounds are characterized by extensive use of ¹³C- and ¹H-NMR. spectroscopy. The steric and statistical problems of selective polysubstitution reactions for the cyclodextrins are discussed, and possible reasons for the observed differences in reactivity between α- and β-cyclodextrins are examined. The dodecabenzoate 3 presents a very marked solvent effect on physical properties (IR. and NMR. spectra, optical rotation); the effects observed may be ascribed to an unusually strong intramolecular network of hydrogen bonds which severely distorts the α-cyclodextrin ring and lowers the symmetry from six-fold to three-fold.     

Sterol sulfates from the Far Eastern holothurianCucumaria japonica

A chloroform-methanol extract of the musculocutaneous sac of the Far-Eastern holothurianC. japonica has yielded a fraction of sterol sulfates (13% of the weight of the extract, 0.8% of the weight of the dry biomass), the main components of which were derivatives of cholest-5-en-3β-ol, 24-methylene-, 24-ethyl-, and 24-ethylidenecholest-5-en-3β-ols, 5α-cholestan-3β-ol, and 24-methyl- and 24-methylene-5α-cholesten-3β-ol; among the minor components were found the sulfates of 24-ethyl-5α-cholestan-3β-ol of cholesta-5,22-dien-3β-ol, of a Δ⁵-C₃₀ sterol, and also of dienic and trienic C₂₆ sterols.     

Conformational Studies of Marine Polyhalogenated α-Chamigrenes Using Temperature-Dependent NMR Spectra. Cyclohexene-ring flipping and rigid-chair cyclohexane ring in the presence of equatorial halogen atoms at C(8) and C(9)

Temperature-dependent NMR spectra indicate that the α-chamigren-3-ones (?) -11 , (+) -12 , (+) -14 (?) -15 , (+) -16, 18 , and 19 bearing equatorial halogen atoms at C(8) and C(9) undergo slow conformational flipping of the envelope-shaped enone ring, while the cyclohexane ring is maintained in the chair conformation. The α-chamigren-3-ols (+) -20 and (+) -21 , obtained by hydride reduction of (+) -12 , behave similarly, with slow half-chair inversion of the cyclohexenol ring. In each case, both conformers are about equally populated and detectable by NMR, except in the case of (+) -15 , where repulsive interactions between Br? C(2) and H_eq?C(7) make the population of the conformer 15b with Me—C(5) faced to H_ax?C(10) so low that it escapes direct ¹H-NMR detection. The energy barriers to these conformational motions are viewed to arise mainly from repulsive interactions between Me—C(5) and the axial H-atoms at C(8) and C(10), while, contrary to previous beliefs, no twist-boat conformations of the cyclohexane ring intervene. Similar conclusions hold for the 4,5-epoxides of both (?) -6 and (+) -7 . Clean Jones oxidatio of (?) -2 to 17 , where the CH₂?C(5) bond is maintained, and acid dehydration-isomerization of the α-chamigrene (+) -21 to the β-chamigrene (+) -24 , reflect the special stability of β-chamigrenes, providing a reason for their frequent occurrence in nature.     

Synthesis and characterization of tris(η~5-cyclopentadienyl-μ-carbonyliron)-μ_3-nitrosyl cluster:X-ray structure of[(η~5-C_5H_5)(μ-CO)Fe]_3(μ3-NO).C_4H_8O

Tris)(η 5-cyclopentadienyl-μ-carbonyl-iron)-μ3-nitrosyl cluster was obtained from the reaction of cyclopentadienyl dicarbonyliron dimer with nitrogen monoxide in xylene. The cluster was characterized by elemental analyses, IR, MS and 1H NMR. The crystal structure of [(η5-C5H5)(μ-CO)Fe]3(μ3-NO).C4H8O was determined by X-ray diffraction analysis. It crystallizes in the orthorhombic space group Pnma, a=9.053(2), 6=10.545(2), c=22.525(4) A, V=2150.3(7) A3, Z=4,Dc=1.68 g.cm-3; structure solution and refinement based on 1141 reflections with I > 3.0 (I) (MoKa, A=0.71073 A) converged at R=0.0540. The infrared absorption band at 1325 cm-1 of the μ3-NO in the cluster, which is red shifted, shows that μ3-NO is activated.     

Synthesis and properties of polyaniline doped with iron-substituted silicotungstate isomers with Keggin structure

Four polyaniline hybrid materials doped with iron-substituted silicotungstate isomers α,?β _i - K_5?n H _n [SiW₁₁Fe(H₂O)O₃₉]?·?xH₂O (β_i?=?β₁, β₂, β₃) were prepared. The materials were characterized by elemental analysis, IR spectra, UV-Vis spectra, scanning electron microscopy (SEM), TG-DTA and X-ray diffraction (XRD). The conductivity and fluorescence were determined and thermal stability was studied. The UV-Vis, IR and XRD results confirm the existence of Keggin anions. Thermal analysis indicates that SiW₁₁Fe/PANI has better thermal stability. The images of scanning electron microscopy (SEM) show that the materials are microporous. The materials exhibit excellent proton conductivity of 8.5?×?10^?2?S?cm^?1 at room temperature (20°C). The spectral data indicate that polyaniline doped with α, β_i-SiW₁₁Fe have similar fluorescence, λ_em?=?418–470?nm, and emit blue light.     

Structure and molecular conformation of tussah silk fibroin films: Effect of methanol

Structural changes of tussah (Antheraea pernyi) silk fibroin films treated with different water-methanol solutions at 20°C were studied as a function of methanol concentration and immersion time. X-ray diffraction measurements showed that the α-helix structure, typical of untreated tussah films, did not change for short immersion times (2 min), regardless of methanol concentration. However, crystallization to β-sheet structure was observed following immersion of tussah films for 30 min in methanol solutions ranging from 20 to 60% (v/v). IR spectra of tussah films untreated and methanol treated for 2 min exhibited strong absorption bands at 1265, 892, and 622 cm^?1, typical of the α-helix conformation. The intensity of the bands assigned to the β-sheet conformation (1245, 965, and 698 cm^?1) increased for the sample treated with 40% methanol for 30 min. Raman spectra of tussah films with α-helix molecular conformation exhibited strong bands at 1657 (amide I), 1263 (amide III), 1106, 908, 530, and 376 cm^?1. Following α → β conformational transition, amide I and III bands shifted to 1668, and to 1241, 1230 cm^?1, respectively. The band at 1106 cm^?1 disappeared and new bands appeared at 1095 and 1073 cm^?1, whereas the intensity of the bands at 530 and 376 cm^?1 decreased significantly. ©1995 John Wiley & Sons, Inc.     

Use of hypervalent iodine oxidation for the C(3)-hydroxylation of chromone,flavone and α-naphthoflavone

C(3)-Hydroxylation of chromone (1a) , flavone (1b) and α-naphthoflavone (4) via acid-catalysed hydrolysis of the corresponding β-methoxy-α-hydroxydimethylacetals (2a, 2b , and 5) formed by iodobenzene diacetate-potassium hydroxide methanol oxidation is described.     

Conformational Studies of Marine Polyhalogenated α-Chamigrenes Using Temperature-dependent NMR spectra inverted-chair and twist-boat cyclohexane moieties in the presence of an axial halogen atom at C(8)

α-Chamigren-3-one (+) -8 bearing an axial CI-atom at C(8) exists as a largely dominant conformer with Me—C(5) at the envelope-shaped enone ring pointing away from CI_ax?C(8) at the cyclohexane ring (= B) in the ‘normal’ chair conformation, as shown by ¹H-NMR. In contrast, the α-chamigren-3-ols (+) -9 and (+) -10 , obtained from hydride reduction of (+) -8 , show a temperature-dependent equilibrium of conformers where the major conformers have ring B in the inverted-chair (and twist-boat for (+) -9 ) conformation to avoid repulsions between Me?C(5) and CI_ax–C(8) (Scheme 1). This is in agreement with the conformation of the epoxidation product (+) -12 of (+) -9 where Me–C(5) is pushed away from CI_ax–C(8) in a ring-B chair similar to that of (+) -8 (Scheme 2). Introduction of a pseudoequatorial Br-atom at C(2) of (+) -8 , as in enone (+) -15 (Scheme 3), does not affect the conformation; but a pseudoaxial Br? C(2) experiences repulsive interactions with H_eq–C(7), as shown by the ¹H-NMR data of the isomeric enone (+) -16 where the ‘normal’-chair conformer Cβ -16 is in an equilibrium with the inverted chair conformer ICβ -16 (Scheme 3). These results and the accompanying paper allow a unifying view on the conformational behavior of marine polyhalogenated α-chamigrenes. This view is supported by the acid-induced isomerization of α-chamigrene (+) -9 (inverted chair) to β-chamigrene (+) -17 (‘normal’ chair; Scheme 4), the driving force being the lesser space requirement of CH₂?C(5) than of Me–C(5). This explains why β-chamigrenes are so common in nature.     

Rate constants for the gas-phase reactions of O3 with a series of monoterpenes and related compounds at 296 ± 2 K

Rate constants for the gas-phase reactions of O₃ with a series of monoterpenes and related compounds have been determined at 296 ± 2 K and 740 torr total pressure of air or O₂ using a combination of absolute and relative rate techniques. Good agreement between the absolute and relative rate data was observed, and the rate constants obtained (in units of 10^?17 cm³ molecule^?1 s^?1) were: α-pinene, 8.7; β-pinene, 1.5; Δ³-carene, 3.8; 2-carene, 24; sabinene, 8.8; d-limonene, 21; γ-terpinene, 14; terpinolene, 140; α-phellandrene, 190; α-terpinene, 870; myrcene, 49; trans-ocimene, 56; p-cymene, <0.005; and 1,8-cineole, <0.015. While these rate constants for α- and β-pinene and sabinene are in good agreement with recent absolute and relative rate determinations, those for the other monoterpenes are generally lower than the literature data by factors of ca. 2–10. The measured rate constants for the monoterpenes are reasonably consistent with predictions based upon the number and positions of the substituent groups around the 〉C?C〈 bond(s).     

Synthèse de sucres aminés ramifiés III. Synthèse et réactions de 1′α-amino-nitrile dérivé du di-O-isopropylidène-1,2:5,6-α-D-ribo-hexofurannosul-3-ose

The addition of cyanohydric acid to 1,2:5,6-di-O-isopropylidene-α-D -ribo-hexofurannos-3-ulose can be sterically controlled. Under kinetic conditions, the allo cyanohydrine epimer is formed, under thermodynamic conditions, the gluco epimer is formed. The configuration of these two products is proved by their chemical reactions. Hydration followed by hydrolysis of the nitrile group of the allo epimer (O-acetyl derivative) gives the 3-C-carboxy-1,2-O-isopropyloidene compound. This product forms the corresponding γ or δ-lactone with hydroxyl ( 5 ) or ( 6 ). On the other hand, after hydrolysis of 5,6-isopropylidene, the 3-O-acetyl derivative of the gluco epimer gives an acetyl migration from position 3 to position 5 and finally to position 6. By reaction of the allo epimer with NH₃ and CN^?, an aminonitrile is formed. The allo configuration is deduced from the above mentioned reaction and from IR. and NMR. data. Several acetylated and trifluoracetylated derivatives of these products are described. The oxidation of the nitrile group to the amide group is possible with both epimeric cyanohydrines and the amino-nitrile.     

Synthesis and Spectra Characteristics of Novel 3‐(para‐Bromophenyl)‐7‐(substituted vinyl) Coumarins

Five new coumarin derivatives ( 5a , 5b , 5c , 5d , 5e ) with extending para‐bromophenyl at the 3‐position and substituted vinyl at the 7‐position were synthesized and characterized by FT‐IR, ¹H NMR, and element analysis. The absorption and fluorescence characteristics of compounds 5a , 5b , 5c , 5d , 5e showed significant dependences on its molecular structure, which possessed large Stokes shifts (up to 8309 cm^?1) and high fluorescence quantum yield (up to 0.80) in CH₂Cl₂. These advantageous spectral properties should allow use in many areas.     

Rate constants for the gas-phase reactions of the OH radical with a series of monoterpenes at 294 ± 1 K

Using a relative rate technique, rate constants for the gas-phase reactions of the OH radical with a series of monoterpenes have been determined in one atmosphere of air at 294 ± 1 K. Relative to a rate constant for the reaction of OH radicals with 2,3-dimethyl-2-butene of 1.12 × 10^?10 cm³ molecule^?1 sec^?1, the rate constants obtained were (in units of 10^?11 cm³ molecule^?1 sec^?1): α-Pinene, 5.45 ± 0.32; β-pinene, 7.95 ± 0.52; Δ³-carene, 8.70 ± 0.43; d-limonene, 16.9 ± 0.5; α-terpinene, 36.0 ± 4.0; γ-terpinene, 17.6 ± 1.8; α-phellandrene, 31.0 ± 7.1; myrcene, 21.3 ± 1.6; and ocimene (acis-, trans-mixture), 25.0 ± 1.9. These are the first quantitative kinetic data reported for many of these monoterpenes. The rate constants obtained are compared with the available literature data and with a priori estimates based on the number and configuration of substituents around the double bond(s). The tropospheric lifetimes of these monoterpenes with OH radicals, NO₃ radicals and O₃ are estimated and compared. Atmospheric lifetimes with respect to reaction with the OH radical are calculated to range from ～0.75 hr for α-terpinene to ～5 hr for α-pinene.     

Stereospecific 1,3 and 1,4 dehydration reactions in the mass spectra of podocarpan-12- and -14-OLS†

Specific deuterium labelling revealed that podocarpan-12α- and -14α-01, representing conformationally well defined cyclohexanols, eliminate water mainly by stereospecific 1,3 reactions involving cis tertiary hydrogens on electron-impact. Dehydration of podocarpan-12ß-0l, which also involves a cis tertiary hydrogen, occurs almost exclusively by a 1,4 reaction. Subsequent decomposition of the various [M – 18]⁺· ions was found to lead to different products, thus explaining some of the intensity differences encountered in the lower parts of the spectra of the epimeric podocarpan-12-ols and -14-ols.     

Radical-initiated homo- and copolymerization of α-methylene-γ-butyrolactone

The kinetics of α-methylene-γ-butyrolactone (α-MBL) homopolymerization was investigated in N,N-dimethylformamide (DMF) with azobis(isobutyronitrile) as initiator. The rate of polymerization (R_p) was expresed by R_p = k[AIBN]^0.54[α-MBL]^1.1 and the overall activation energy was calculated as 76.1 kJ/mol. Kinetic constants for α-MBL polymerization were obtained as follows: k_p/k_t^1/2 = 0.161 L^1/2 mol^?1/2·s^?1/2; 2fk_d = 2.18 × 10^?5 s^?1. The relative reactivity ratios of α-MBL(M₂) copolymerization with styrene (r₁ = 0.14, r₂ = 0.87) were obtained. Applying the Q–e scheme led to Q = 2.2 and e = 0.65. These Q and e values for α-MBL are higher than those for MMA     

Multichain copoly(α-amino acid). I. Multichain copoly(α-amino acid) prepared by reaction of copoly(L-lysine γ-methyl-L-glutamate) with N-carboxy anhydride of Nϵ-carbobenzyloxy-L-lysine

Polymerization of the N-carboxy anhydride of N^?-carbobenzyloxy-L -lysine in the presence of multifunctional polymeric initiator, copoly(L -lysine γ-methyl-L -glutamate) was studied in N,N-dimethylformamide containing 3% (v/v) of dimethyl sulfoxide. Multichain copoly(α-amino acid), i.e., multi-N^?-poly(N^?-carbobenzyloxy-L -lysine)copoly(L -lysine γ-methyl-L -glutamate), was obtained with linear poly(N^?-carbobenzyloxy-L -lysine) as by-product that could be removed by reprecipitation as was evidenced by gel-permeation chromatography. The degree of polymerization of the branch polymer chains estimated by the osmometric molecular weight determination and amino acid analysis was between 20 and 60, which decreased with increasing lysine content of the polymeric initiator. The stability of α-helical conformation of the multichain copoly(α-amino acid) was studied in the chloroform–dichloroacetic acid system at 25°C by the ORD technique. The α-helical conformation of poly(N^?-carbobenzyloxy-L -lysine) branches was less stable than those of linear poly(N^?-carbobenzyloxy-L -lysine) and the core molecular chains of the multichain copoly(α-amino acid).