Search

Cyclocondensation of salicylaldehydes with alkyl acetoacetates and 2-aminobenzothiazoles or 2-amino-5-methylthiazole under classical Biginelli reaction conditions gives rare hetarylamino substituted 2,2′-spirobischromanecarboxylate derivatives. The mechanism and observed stereoselectivity of the unexpected pseudo-four-component process are discussed.

Cyclocondensation of salicylaldehydes with alkyl acetoacetates and 2-aminobenzothiazoles or 2-amino-thiadiazole/thiazoles under l -proline catalysis gives 4-hetarylamino substituted chromanecarboxylate derivatives. The mechanism involving the Mannich/hemiketalization cascade reaction and the observed stereoselectivity of the three component process are discussed.

Studies of the middle-aged hippocampus may clarify the early mechanisms of aging and may lead to timely initiation of treatment for age-related cognitive impairments. Young (2-m/o) and middle aged (15- and 17-m/o) rats were used with the aim to characterize early differences in electrophysiological properties, morphometrical changes and 1H-nuclear magnetic resonance (NMR) metabolite content in the hippocampus. A decrease of the neuronal number accompanied by reduced width of the CA1 pyramidal cell layer was observed in middle-aged rats which may correspond to their reduced neurotransmission found in the CA3-CA1 synapse. An absolute value of mean magnitude of baseline field potential as well as of response obtained 51–60 min after high frequency stimulation was significantly lower in the middle-aged rats. The measurement of 1H-NMR metabolite content in hippocampal extracts of 2- and 17-m/o rats revealed that none of the sixteen metabolites identified can serve as a marker for middle-age-related changes. Functional and morphological changes are observed in middle-aged hippocampus. Therefore, 15–17-m/o rats could serve as proper animal model in studies focused on aging. Further studies aimed at timely prevention of early changes in the brain may contribute in slowing down of physiological brain aging.

Chiral nitrones 13-15 prepared from D-isoascorbic acid were found to effectively undergo an SmI2-mediated radical addition to methyl acrylate affording γ-N-hydroxylamino esters 19-22 with high diastereomeric control. The unsubstituted nitrone 14 afforded in the SmI2-induced coupling with methyl acrylate the γ-N-hydroxylamino ester 21 as minor product. The pyrrolidinones 23-25 were prepared in a single step from 19 and 22 involving N-O bond cleavage with Zn/AcOH or SmI2 and subsequent spontaneous cyclization.

Search for indicators of neurodegenerative disorders is a hot topic where much research remains to be done. Our aim was to determine proton nuclear magnetic resonance ((1)H-NMR) spectra of brain metabolites in the trimethyltin (TMT) model of neurodegeneration. Male Wistar rats were subjected to TMT or saline and were sacrificed on day 3 or 24 after administration. (1)H-NMR spectrum was measured on the 600 MHz Varian VNMRS spectrometer in nano-probe in the volume of 40 μl of hippocampal extracts. TMT administration resulted in reduction of the hippocampal weight on day 24. Of the sixteen identified metabolite spectra, decreased aspartate and increased glutamine contents were observed in the initial asymptomatic stage of neurodegeneration on day 3 in hippocampal extracts of TMT exposed rats compared to sham animals. Increased myo-inositol content was observed on day 24. The presented data provide further knowledge about this experimental model and putative indicators of neuronal damage.

The HPLC analysis of diazepam conformers was carried out in the temperature range 273–313 K, increment 10 K. The pH of the mobile phase was 3.3; 5.5; 5.5 (Ic=const; 6.5; 6.5 Ic=const.). The various flow rates of 0.2; 0.5; 1.0; mL/min were used. Chiral stationary phase based on β‐cyclodextrin (ChiraDex) was used for separation of diazepam. The influence of temperature, flow rate, pH of mobile phase, and ionic strength on the retention and elution profile on two peaks of diazepam conformers were studied. After that, the chiral β‐cyclodextrin (0.001 mol/L; 0.003 mol/L; 0.005 mol/L) was added into the mobile phase. The increasing amount of β‐cyclodextrin in the mobile phase caused the disappearance of the first peak. The complete chiral separation of diazepam was not possible because of simultaneous interconversion. The plateau between two peaks of diazepam appeared in the whole range studied, any inhibitory effects of chromatographic conditions (pH of mobile phase, temperature, flow rate, ionic stre...

Acridin-9-yl hydrazine upon treatment with various isothiocyanates (RNCS, R = methyl, allyl, phenyl, p-methoxy phenyl, and p-nitro phenyl) yielded the corresponding thiosemicarbazides with acridine substituted on the carbazide-type side. The alkyl-substituted compounds were present in solution as equilibria consisting of the major H-10, H-12 tautomer (either E or Z or both about the C13-N14 bond) and the minor H-10, SH tautomer (either E or Z or both). The major species for the aromatic-substituted compounds was the H-10, H-12 E tautomer, with the evident minor species being the H-10, H-12 Z tautomer. The thiosemicarbazides were each quantitatively converted into the analogous semicarbazides upon treatment with mesitylnitrile oxide wherein all structures were present in solution as the H-10 tautomers with Z conformation about the C13-N14 bond. Methylation of the compounds with methyl iodide yielded S-methylated compounds wherein the Z configuration dominated in each case over the E configuration along the N12-C13 double bond. Treatment of the thiosemicarbazides with methyl bromoacetate resulted in the formation of 1′,3′-thiazolidin-4′-ones wherein the Z configuration predominated in each case over the E configuration along the N12C13 double bond. With bromoacetonitrile as the bifunctional electrophile, the initial 1′,3′-thiazolidin-4′-imines that formed spontaneously underwent Dimroth-type rearrangement to the regiosiomeric 1′,3′-thiazolidin-4′-imines.

This study presents the comparison of conformational behaviour of two similar push–pull ethylenes in which the possibility to form an intramolecular hydrogen bond exists. The IR, Raman and NMR spectroscopic studies as well as ab initio MP2 and DFT B3LYP theoretical calculations using 6-31G** basis set confirmed that the presence of intramolecular hydrogen bond has an important influence on conformational behaviour of such type compounds. 3-methylamino-2-acetyl propenenitrile (MAAPN) H 3 C NH CH C(CN)(COCH 3 ) was prepared as pure Z -isomer with intramolecular hydrogen bond while 3-methylamino-2-methylsulfonyl propenenitrile (MASPN) H 3 C NH CH C(CN)(SO 2 CH 3 ) as pure E -isomer. MAAPN in polar solutions partially underlies to the isomerization. Such process has not been observed for MASPN which exists in solution in two conformers with the anti and syn orientation of the methylamino group towards the C C double bond, anti conformer being about 2.0 ± 0.4 kJ mol −1 more stable. The vibrational spectra of studied molecules were assigned on the base of normal coordinate calculations and potential energy distribution (PED). The use of different polarizable continuum models (IPCM, PCM) included in SCRF theory leads to controversial results in ground-state energy calculations in solutions of various polarity.

The regio- and stereoselectivity of cycloadditions of the nitrone 1a and the chiral, sugar-derived nitrones 13a and 13b with 3-(prop-2-enoyl)-1,3-oxazolidin-2-one (2) depends on the nature of the Lewis acid catalyst used. Addition of Lewis acid reverses the regioselectivity of the cycloaddition, and improves the anti-diastereoselectivity in the case of chiral nitrones. The sterically favored isoxazolidin-5-yl-substituted adducts 3, 4, and 14–17 are produced as the major products in the absence of Lewis acid, while the electronically favored regioisomers with isoxazolidin-4-yl substituents (5, 6, and 18–21, respectively) are obtained as major products in the [Ti(OiPr)2Cl2] catalyzed reactions. The reactions of nitrone 13b with 2 in the presence of other Lewis acids such as ZnCl2, ZnBr2, ZnI2 and MgI2/I2 gave both regioisomeric pairs of the diastereoisomers, favoring the 4-substituted congeners. The diastereoisomeric isoxazolidines 3a–6a were reduced with NaBH4 in THF/H2O with subsequent desilylation to yield the separable diols 9–12. Reduction of the diastereoisomeric isoxazolidines 19a and 18a afforded the chiral alcohols 23 and 22, the latter of which was analyzed by X-ray crystallography.

The isomers and conformers of six push–pull enamines: 3-dimethylamino-, 3-methylamino- and 3-amino-2-acetyl propenenitrile [(H 3 C) 2 N–CH C(CN)(COCH 3 ), H 3 C–NH–CH C(CN)(COCH 3 ) and H 2 N–CH C(CN)(COCH 3 )] and 3-dimethylamino-, 3-methylamino- and 3-amino-2-methylsulfonyl propenenitrile [(H 3 C) 2 N–CH C(CN)(SO 2 CH 3 ), H 3 C–NH–CH C(CN)(SO 2 CH 3 ) and H 2 N–CH C(CN)(SO 2 CH 3 )] have been studied experimentally by vibrational and NMR spectroscopy and theoretically by the ab initio calculations at MP2 level in 6-31G** basis set. The IR and Raman spectra of all compounds as a solid and solute in various solvents have been recorded in the region 4000–50 cm −1 . The NMR spectra were obtained in chloroform and DMSO at room temperature. All six compounds have been prepared by the same way. NMR spectra revealed that both dimethylamino compounds were prepared as a pure E isomers whereas in the case of methylamino compounds the 3-methylamino-2-methylsulfonyl propenenitrile was prepared also as a pure E isomer but 3-methylamino-2-acetyl propenenitrile as a pure Z isomer. Also 3-amino-2-methylsulfonyl propenenitrile was obtained as a pure the E isomer, but 3-amino-2-acetyl propenenitrile as a mixture of both E and Z isomers. Confomational possibilities of studied compounds are given only by the rotation of the acetyl and methylamino groups. Vibrational spectra revealed existence of two conformers with Z and E orientation of acetyl group for 3-dimethylamino-2-acetyl propenenitrile. Two conformers with anti or syn orientation of methylamino group for 3-methylamino-2-methylsulfonyl propenenitrile have been confirmed by vibrational and NMR spectra, but only one conformer with anti orientation of methylamino group for 3-methylamino-2-acetyl propenenitrile in chloroform solution and in solid phase was found. For latter compound the additional isomer/conformer was detected in more polar solvents (acetonitrile/DMSO). These experimental findings have been supported by ab initio solvent effect calculations.

Alkyl 1-(2-alkoxy-2-oxoethyl)-4-formyl-1H-pyrrole-2-carboxylates 3a and 3b (alkyl = Me, Et), prepared from the corresponding alkyl 4-formyl-1H-pyrrole-2-carboxylates 2a and 2b, have been modified to other derivatives of the same structural pattern. A series of β-pyrrolylalkenes 4–8 was obtained from pyrrole 3b and various C–acids. Derivatives 2 and 3 have been also used as synthons for polysubstituted 4-(1H-pyrrol-3-yl)-1,4-dihydropyridines 9–12 under the conditions of the standard and the modified Hantzsch’s dihydropyridine synthesis or by regioselective alkylation of the 1,4-dihydropyridine skeleton.

The understanding of thermo-mechanical degradation of poly(vinyl alcohol)s (PVAs) during thermoplastic processing is insufficient and deserves more attention due to the high potential of this technology. In this contribution the experimental data are provided revealing the effect of melt processing on properties of PVAs differing in degree of hydrolysis. NMR, FTIR, titration and size exclusion chromatography were used to demonstrate the effect of extrusion time on average length of the respective blocks and mutual ratio of vinyl acetate–vinyl alcohol monomer units, content of double bonds, amount of liberated acetic acid and molecular weight distribution. Partially hydrolysed PVAs are less resistant to degradation than fully hydrolysed PVAs, which primarily corresponds to the presence of vinyl acetate groups. Other factors, like microstructural heterogeneities and the presence of double bonds, may significantly influence the stability of partially hydrolysed samples. Addition of benzoic acid was used to prove that the mechanism of degradation involves the acidic catalysis by acetic acid liberated from vinyl acetate units.

1,3-Dipolar cycloadditions of chiral nitrones to Baylis-Hillman adducts (β-hydroxy-α-methylene esters) proceed with complete regioselectivity in good yields to afford the corresponding diastereomeric 3,5,5-trisubstituted isoxazolidines. Attack of the dipole from the less sterically hindered side of the dipolarophiles affords C-3/C-5 cis isoxazolidines as the predominant isomers. The strong preference for the C-3/C-5 cis isoxazolidines provided more sterically demanding O-tert-butyldimethylsilylsubstituted nitrone 2. Addition of Lewis acids accelerates the reaction and increases the portion of C-3/C-5 trans isoxazolidines. Microwave irradiation accelerates the reaction, but it produces only a small effect on the diastereoisomeric product ratio.

Chiral nitrones derived from l -valine react with methyl acrylate to afford the corresponding diastereomeric 3,5-disubstituted isoxazolidines. The dibenzylsubstituted nitrone gave also 3,4-disubstituted isoxazolidine in 4% yield, additionally. The stereoselectivity was dependent on the steric hindrance of the nitrone and reaction conditions. High pressure decreased the reaction time of the cycloadditions. The major products were found to have the C-3/C-6 erythro and C-3/C-5 trans relative configuration. The major cycloadduct undergoes N–O cleavage and deprotection to a chiral diaminodiol derivative.

The new chiral terminal alkenes derived from cyclic acetals of D-erythrose 1-3 and D-threose 5, 6 were prepared. The alkenes 1, 2 and 5 react with chiral nitrones to afford the corresponding diastereomeric isoxazolidines 19-21. The stereoselectivity was dependent on the steric hindrance of the nitrone. In all cases the cycloadditions are endo-selective. The major products were found to have the C-3/C-4 erythro- and C-3/C-3a cis-configuration. Its formation can be rationalized by a less hindered endo-attack of the (Z)-nitrone in an antiperiplanar manner with respect to the largest group of the cyclic acetal.

2-Alkoxy-3-(arylaminomethylene)chroman-4-ones and 3-(aryliminomethyl)chromones were prepared by acid catalyzed reaction of 3-formylchromones with aromatic amino carboxylic acids in alcoholic reaction media. The results of the kinetic study have confirmed that 3-(aryliminomethyl)chromones are formed from 2-alkoxy-3-(arylaminomethylene)chroman-4-ones. The dependence of the reaction rate on reactant structure, the reaction media and the concentration of catalyst has been studied. In contrast to the alcoholic media reaction, the same reaction in dry aprotic reaction media yielded only 2-hydroxy-3-(arylaminomethylene)chroman-4-ones. No 3-(aryliminomethyl)chromones were isolated in that case.

1,3-Dipolar cycloadditions between the D-erythrose and D-threose derived nitrones and methyl acrylate proceed in a regiospecific manner to afford the corresponding 3,5-disubstituted diastereomeric isoxazolidines in good yields. The stereoselectivity was dependent on the steric hindrance of the nitrone. The major products were found to have the C-3/C-4' erythro and C-3/C-5 cis relative configuration. Its formation can be rationalized by less hindered endo attack of the Z-nitrone in an antiperiplanar manner with respect to the largest group of the cyclic acetal.

Stereoselectivity of the reaction of N-benzyl-C-ethoxycarbonyl nitrone (3) with (S)-5-hydroxymethyl-2(5H)-furanone (2a) and its 5-alkoxy substituted derivatives 2b-f was investigated. The reaction proceeds in a highly face-selective manner, the products 4–6 resulting from approach anti to the hydroxymethyl or alkoxymethyl group of the dipolarophile. The exo-stereoselectivity increases as the size of protective group attached to lactone (2b-f) increases. Endo-exo diastereoselectivity is affected significantly by the solvent. Microwave irradiation strongly accelerates the reaction with little effect on the diastereoselectivity to give the syn adduct 8a in addition to anti cycloadducts 4a–6a.

The new nitrones derived from cyclic acetals of D-erythrose (2a-c) and D-threose (8) react with styrene to afford the corresponding 3,5-disubstituted diastereomeric isoxazolidines 3-6 and 9-12. The stereoselectivity was dependent on the steric hindrance of the nitrone. The major products 3a-c (55-58 %) and 9 (73 %) were found to have the C-3/C-4' erythro and C-3/C-5 cis relative configuration by X-ray analysis. Its formation can be rationalized by less hindered endo attack of the Z-nitrone in an antiperiplanar manner with respect to the largest group of the cyclic acetal. (C) 1999 Elsevier Science Ltd. All rights reserved.

The infrared absorption bands of the C*O stretching vibration and the 13C NMR chemical shifts were measured for a series of nine substituted 3,4-diphenyl-cyclobut-3-ene-1,2-di-ones in CHCl3, CDCl3, and partially in CCl4. The AM1 charge densities, bond orders, and valence angles were calculated for the optimized geometry. Good to satisfactory mutual correlations were found between the arithmetic means of the wave numbers of symmetric and asymmetric C*O stretching vibrations, Hammettσ constants, rate coefficients, and enthalpies of activation of the base-catalyzed ring fission as well as the AM1 oxygen charge densities and bond orders at the carbonyl groups. The results show that the factors controlling the reactivity of these compounds and the structural and IR spectroscopic properties of the C*O groups must be the same. The correlation between the wave numbers of symmetric and asymmetric C*O stretching vibrations affords a slope of a=1.069 which points to the existence of a strong cross-conjugation effect in the cyclobutenedione ring. The correlation of the wave number separation of the absorption bands of symmetric and asymmetric C*O stretching vibrations (Δv(C*O)) for various cyclic diketones enabled the prediction of the angle γ=83° between the bond vectors of the two carbonyl groups in the cyclobutenedione rings, which is in satisfactory agreement with the value calculated by the semiempirical AM1 method.

A new compound was isolated from the reaction mixture after O-demethylation of 6-O-acetyl-10α-acetoxycodeine with boron tribromide. The structure of this compound, 10α-hydroxy-β-isomorphine, was elucidated by spectral data, and its spatial arrangement was deduced from an NOE experiment. Capillary zone electrophoresis was used for separation of morphine and its 10-hydroxy analogues.

Triton B catalyzed Michael addition of nitromethane on esters of α,β-unsaturated acids 1 has been studied. The course and regioselectivity of the reaction is discussed in the view of structure of products 2a-g, 3a-g, 4g, f, 5g, f, assessed by GC/MS, NMR and IR spectroscopy and by MOPAC 6 (AM1) calculations, respectively.

[2E,7E]-4,9-dioxo-2,7-decadienoic, [2E,7E]-9-oxo-2,7-decadienoic and [2Z,4E]-2-methyl-2,4-hexadienoic acids were isolated from the filtrate ofPenicillium vermiculatum Dang. The presence of [2E,2′E,7S,7′E]-4,9-dioxo-7-(4′,9′-dioxo-2′,7′-decadienoyloxy)-2-decenoic acid was confirmed by chromatography. HPLC was used for the determination of these acids in the cultivation medium.

The reduction of condensed imides 1 with sodium borohydride proceeds regio- and stereoselectively to yield the hydroxylactams 2, 3 and 4. AM1 calculations of the reactants and products reveal that the regiochemistry of the reductions seems to be controlled by both electronic and steric effects. The regio- and stereoselectivity of the reductions are dramatically improved by the presence of magnesium perchlorate. This is interpreted in terms of a chelate complex formation between the carbonyl group, isoxazoline oxygen atom and magnesium ion. The presence of p-toluenesulfonic acid (p-TsOH) also improves the regioselectivity, but lowers the chemoselectivity.

Synthesis of β-chloroferroceneacroleins and β,β′-dichloroferrocenediacroleins starting from acetyl-, 1,1′-diacetyl, 1-phenylacetyl- and 1,1′-diphenylacetylferrocene is described. The α-phenyl derivatives of β-chloroferroceneacroleins were prepared as the mixture of E,Z; E,E and Z,Z isomers. All ferroceneacroleins were isolated in pure state and their configuration was elucidated by means of 1H- and 13C NMR spectroscopy and also confirmed by quantum chemical calculations. The acid catalysed E/Z isomerisation of the α-phenyl-β-chloroferroceneacroleins and diacroleins was observed and briefly studied.

A route has been developed for the synthesis of enantiomerically and diastereomerically pure trihydroxylated pyrrolizidines. A chiral sugar derived nitrone undergoes diastereoselective dipolar cycloaddition with methyl acrylate to afford erythro-cis isoxazolidine a suitable cycloadduct undergoes N-O cleavage and recyclization to (1S.2R.6R.7aS)-trihydroxylated pyrrolizidine

The reduction of condensed imides 1 with sodium borohydride proceeds regio- and stereoselectively to yield the hydroxylactams 2, 3 and 4. AM1 calculations of the reactants and products reveal that the regiochemistry of the reductions seems to be controlled by both electronic and steric effects. The regio- and stereoselectivity of the reductions are dramatically improved by the presence of magnesium perchlorate. This is interpreted in terms of a chelate complex formation between the carbonyl group, isoxazoline oxygen atom and magnesium ion. The presence of p-toluenesulfonic acid (p-TsOH) also improves the regioselectivity, but lowers the chemoselectivity.

Stereoselectivity of the reaction of N-benzyl-C-ethoxycarbonyl nitrone (3) with (S)-5-hydroxymethyl-2(5H)-furanone (2a) and its 5-alkoxy substituted derivatives 2b-f was investigated. The reaction proceeds in a highly face-selective manner, the products 4–6 resulting from approach anti to the hydroxymethyl or alkoxymethyl group of the dipolarophile. The exo-stereoselectivity increases as the size of protective group attached to lactone (2b-f) increases. Endo-exo diastereoselectivity is affected significantly by the solvent. Microwave irradiation strongly accelerates the reaction with little effect on the diastereoselectivity to give the syn adduct 8a in addition to anti cycloadducts 4a–6a.

Oxidation of furan-2-carboximidamides 8 by (dicarboxyiodo)benzenes gives N1-acyl-N1-(2-furyl)ureas 9via rearrangement to a carbodiimide. Thermolysis of eleven ureas 9 gave the corresponding 2-acylaminofurans 10, which cannot be made from the free amines owing to their high instability. When oxidation of the corresponding benzo[b]furan derivatives 12 was investigated a new type of product was isolated, in addition to the expected ureas 14, and these were shown to be benzo[4,5]furo[2,3-d]pyrimidine derivatives 15. The mechanism of formation of these products must involve reaction of the carbodiimide intermediate with the amidine precursor and cyclisation of the resulting guanidine derivatives 19. The corresponding tetraphenylguanidine 21 was prepared and underwent thermal cyclisation but the quinazoline derivative formed 23 was shown to occur via an alternative cyclisation mechanism. The structures of cyclisation products 15 and 23 were confirmed by X-ray crystallography. N-(2-Furyl)acetamide 10a readily undergoes cycloaddition reactions with electron-deficient alkynes to give phenols after spontaneous ring opening. Observed regioselectivity is in agreement with the results of AM1 molecular orbital calculations. Reaction of the amide 10a with Lawesson’s reagent gave the thioamide 26.

The antiradical activity, protective effect against lipid peroxidation of liposomal membrane, and inhibitory effect on whole blood reactive oxygen species (ROS) liberation of Glycyrrhiza glabra crude extract and glycyrrhizin, its major compound, were assessed. The liquorice extract showed significant activity in all the three assay systems used in a dose dependent manner. It displayed remarkable reactivity with free stable 1,1'-diphenyl-2-picrylhydrazyl (DPPH) radical, inhibitory efficacy in peroxidatively damaged unilamellar dioleoyl phosphatidylcholine (DOPC) liposomes, and inhibition of ROS chemiluminescence, generated by whole blood, induced by both receptor-bypassing stimuli (PMA) and receptor operating stimuli (Opz) in the ranking order of stimuli PMA> Opz. These activities may be attributed to phenolic antioxidants involving isoflavan derivatives, coumarins and chalcones. Nonetheless, triterpene saponin glycyrrhizin exhibited no efficacy in the system of DPPH reaction and peroxidation of liposomal membrane, and negligible inhibition of chemiluminescence generated by inflammatory cells. These results indicate that the mechanism of anti-inflammatory effect of glycyrrhizin most probably does not involve ROS and this major constituent is not responsible for the inhibition effects of liquorice extract on neutrophil functions.

Trichoderma viride was capable of growth and conidiation in the presence of high concentrations of the uncoupler 3,3′,4′,5-tetrachlorosalicylanilide (up to 100 µmol·L–1) and of the respiration inhibitor mucidin (up to 100 µmol·L–1) in both submerged and surface cultivation. When vegetative mycelia were cultivated on the solid Czapek-Dox medium with yeast autolysate under an anaerobic and CO2-containing atmosphere, the growth was observed only rarely but the microorganism survived as long as 3 months under these conditions. Major products of metabolism of both aerobic and anaerobic submerged mycelia were identified by means of1H-NMR measurements. Major products excreted to the medium under aerobic conditions were succinic and citric acids. Major metabolites present in the submerged mycelia were γ-aminobutyric (and glutamic) acid and alanine. Under anaerobic conditions, citric acid was not excreted into the medium but ethanol appeared. Its production could not be increased upon increasing the sugar concentration. The appearance of secondary metabolites was found to be modified by oxygen availability during the mycelial growth. Results suggest that the vegetative form of T. viride is capable of fermentative metabolism characterized by the production of ethanol and succinate and that the excretion of carboxylic acids is developmentally regulated and modified by oxygen availability.Key words: Trichoderma, mycelia, anaerobiosis, citrate, succinate, ethanol, GABA.

1,3-Dipolar cycloadditions of chiral nitrones to Baylis-Hillman adducts (β-hydroxy-α-methylene esters) proceed with complete regioselectivity in good yields to afford the corresponding diastereomeric 3,5,5-trisubstituted isoxazolidines. Attack of the dipole from the less sterically hindered side of the dipolarophiles affords C-3/C-5 cis isoxazolidines as the predominant isomers. The strong preference for the C-3/C-5 cis isoxazolidines provided more sterically demanding O-tert-butyldimethylsilylsubstituted nitrone 2. Addition of Lewis acids accelerates the reaction and increases the portion of C-3/C-5 trans isoxazolidines. Microwave irradiation accelerates the reaction, but it produces only a small effect on the diastereoisomeric product ratio.

The stereoselectivity of nitrone cycloaddition with enol ethers (2 and 4) depends upon the nature of the Lewis acid. The 1,3-dipolar cycloaddition of nitrones (1, 6 and 8) with enol ether (2) under the catalysis of AlMe 3 and Et 2 AlCl proceeded diastereoselectively; whereas nitrone substitution with TBDPS reverses the diastereoselectivity of the cycloaddition. The oxidative ring-opening of isoxazolidines (3 and 9) with the treatment of benzyl bromide results new β-amino acid esters (11, 13 and 15).

Oxidation of furan-2-carboximidamides 8 by (dicarboxyiodo)benzenes gives N1-acyl-N1-(2-furyl)ureas 9via rearrangement to a carbodiimide. Thermolysis of eleven ureas 9 gave the corresponding 2-acylaminofurans 10, which cannot be made from the free amines owing to their high instability. When oxidation of the corresponding benzo[b]furan derivatives 12 was investigated a new type of product was isolated, in addition to the expected ureas 14, and these were shown to be benzo[4,5]furo[2,3-d]pyrimidine derivatives 15. The mechanism of formation of these products must involve reaction of the carbodiimide intermediate with the amidine precursor and cyclisation of the resulting guanidine derivatives 19. The corresponding tetraphenylguanidine 21 was prepared and underwent thermal cyclisation but the quinazoline derivative formed 23 was shown to occur via an alternative cyclisation mechanism. The structures of cyclisation products 15 and 23 were confirmed by X-ray crystallography. N-(2-Furyl)acetamide 10a readily undergoes cycloaddition reactions with electron-deficient alkynes to give phenols after spontaneous ring opening. Observed regioselectivity is in agreement with the results of AM1 molecular orbital calculations. Reaction of the amide 10a with Lawesson’s reagent gave the thioamide 26.