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A series of new thienyl ring containing analogues of nelfinavir and saquinavir with different substitution patterns were synthesized from suitable enantiopure diols. Their inhibitory activity against wild type recombinant HIV-1 protease was evaluated. In general thienyl groups spaced from the core by a methylene group gave products showing IC(50) in the nanomolar range, irrespective of the type and the substitution pattern of the heterocycle. The range of activity of the two most active compounds is substantially maintained or even increased against two commonly selected mutants, under drug pressure, such as V32I and V82A.

Regio- and stereocontrolled alkoxy mercuration of α,β-unsaturated esters allows direct access to 1,3-syn diols in good yields. Demercuration of adducts leads to 1,3 skipped dihydroxy esters, alcohols, and α-halo esters. The deprotection of acetonide with Amberlyst 15 on 1,3-syn-dihydroxy esters gives the corresponding δ-lactones.

Steam explosion of corn stalk in the presence of 3% sulphuric acid at 200 °C for 5 min gave the highest recovery of lignin. Lignin has Mw = 2640 and Mz = 93,994. In the UV spectrum absorptions at λ = 231 and 280 nm were recorded. 1H NMR spectrum of lignin showed signals attributable to cinnamaldehyde units, guaiacyl units, and syringyl units. Syringyl and guaiacyl units are in 1:1 ratio. 13C NMR spectrum showed signals for guaiacyl, syringyl, and p-hydroxyphenyl units. The spectrum showed a prevalence of guaiacyl units. The 13C NMR spectrum is in agreement with the presence of cinnamic units. The same characterization was performed on lignin from pine. The irradiation of lignin from pine from steam explosion process in the presence of oxygen, in conditions described for the formation of superoxide ion, for different irradiation time was followed isolating the lignin and determining the average molecular weight. The experiments showed that, until 8 h irradiation, Mn decreases, while Mw and Mz increases. After 8 h irradiation an inverse behaviour was observed, with an increase of Mn and a decrease of Mw and Mz. These results are in agreement with an initial polymerization process followed by a photoinduced degradation. Ozonization was carried out in acetonitrile–methanol solution. The reaction showed a zero-order kinetics. After 50 min the average molecular weight of lignin is the half. The reaction mixture was analyzed by using GC–MS. Oxalic acid was determined.

Lignin powder, obtained from an abundant and low-cost source, straw, through a low-environmental-impact process, steam explosion, was used for the preparation of blends with a biodegradable polyester, poly(e-caprolactone) (PCL), with an innovative technique, high-energy ball milling. Lignin strongly stabilized PCL against UV radiation. The modulus of the blends increased with the addition of lignin; nevertheless, the elongation at breaking decreased. Through thermal characterization (differential scanning calorimetry and dynamic mechanical analysis), lignin and PCL were found to be immiscible. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008

Starting from a single suitable functionalised epoxide, a highly efficient stereoselective synthesis of d - erythro -sphingosine and d - lyxo -phytosphingosine is described. The approach allows the formal preparation of all stereoisomers of these sphingoid structures.

Optimized conditions for the catalytic asymmetric dihydroxylation have been applied to thiophene and benzothiophene containing acrylates and crotonates to afford the corresponding diols in good overall yields and good to excellent enantiomeric excess. The products obtained were revealed to be useful intermediates in peptidomimetic synthesis.

A stereoselective synthesis of the C1-C11 fragment of macrolactin A, using original approaches for the introduction of the Z,E-diene stereochemistry and the C-7 stereogenic center, is reported. The adopted strategy has allowed us to build up the fragment by the assembly of three key intermediates via cross-metathesis, Still-Gennari, and Wittig olefinations. Opening of the commercially available chiral benzyl glycidol epoxide to the corresponding homoallylic alcohol introduced the C-7 chiral center. A cross-metathesis reaction was used to create the C5-C4 E double bond. The Still-Gennari reaction introduced the 2Z,4E-diene moiety and finally the Wittig reaction with a propargylic triphenylphosphorane introduced directly the 1,3-enyne unit in a highly efficient stereoselective fashion.

The reaction between an iminophosphorane with furan-2-carbaldehyde, thiophene-2-carbaldehyde, furan-3-carbaldehyde, and thiophene-3-carbaldehyde at 60 degrees C gives the corresponding trans imines in 53-84% yields, while the same reaction at 100 degrees C gives a mixture of the corresponding trans and cis imines. Whether the iminophosphorane reacted with 5-nitrofuran-2-carbaldehyde or 5-nitrothiophene-2-carbaldehyde only the trans imines were obtained in 85-89% yields. The irradiation of the imines obtained from thiophene-2-carbaldehyde and thiophene-3-carbaldehyde gave the corresponding photocyclization products. Cis/trans stereochemistry of the imines can be assigned simulating the UV-vis spectra. In the case of the imine from furan-2-carbaldehyde the computed spectra are characterized by an intense absorption at 361 and 357 nm respectively for the trans-1 and trans-2 structures. No other absorptions of comparable intensity have been predicted: the agreement with the experimental spectrum can be considered good. Furthermore, the experimental weak peaks at 280 and 270 nm can be associated to the computed transitions at 278 and 260 nm for the trans-1 isomer. Several minima of the energy surface can be assigned to the cis isomer, and they all present a very similar energy. The structures of the cis-1 and cis-2 isomers present quite coincident computed electronic spectra. In both cases, the computed spectrum shows two principal features. For the cis-1 structure, the first characteristic absorption is located at 414 nm and the second one at 284 nm. For the cis-2 structure, the first feature is located at 412 nm and the second one at 286 nm. The second transition is computed somewhat more intense. The experimental spectrum could be the consequence of similar populations of the planar cis structure (cis-3) and nonplanar cis structures (cis-1, cis-2, and their enantiomers).

A benzothiazolyl TMS-propargylic sulfone was subjected to one-pot Julia olefinations with a variety of aliphatic and aromatic aldehydes. Predominant Z-selectivity up to 98:2 and good chemical yields were obtained in a facile route to the desired 2-1,3-enyne moieties.

Amberlyst 15 is an efficient catalyst for the reaction of aryl-substituted oxiranes with acetone to prepare 2,2-dimethyl-1,3-dioxolanes in high yields. trans-2,3-Diaryloxiranes afford trans-acetonides enantiospecifically at room temperature, and the use of enantiopure 2,3-diaryloxiranes results in no loss of stereochemical integrity in the resulting trans-acetonides. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

The stereocontrolled condensation of methyl ketones to trans alpha,beta-aziridine aldehydes creates functionalized aldols, valuable precursors for different amino hydroxylated structures, such as amino alcohols, amino diols, alpha-tetrahydrofuryl amides, and alpha-furyl amides.

Lignin, obtained through steam explosion from straw, was completely characterized via elemental analysis, gel permeation chromatography, ultraviolet and infrared spectroscopy, and 13 C and 1 H nuclear magnetic resonance spectrometry. Polyurethanes were obtained by treating steam-exploded lignin from straw with 4,4'-methylenebis(phenylisocyanate), 4,4'-methylenebis(phenylisocyanate) -ethandiol, and poly(1,4-butandiol)tolylene-2,4-diisocyanate terminated. The obtained materials were characterized by using gel permeation chromatography, infrared spectroscopy, and scanning electron microscopy. Differential scanning calorimetry analysis showed a T g at -6°C, assigned to the glass transition of the poly(1,4-butandiol) chains. The presence of ethylene glycol reduced the yields of the polyurethanes. The use of the prepolymer gave the best results in polyurethane formation. Steam-exploded lignin was used as the starting material in the synthesis of polyesters. Lignin was treated with dodecanoyl dichloride. The products were characterized by using gel permeation chromatography, infrared spectroscopy, 13 C and 1 H nuclear magnetic resonance spectrometry, and scanning electron microscopy.

Singlet oxygen mediated degradation of lignin was performed on lignin from steam exploded straw, organosolv lignin and alkali lignin. The kinetics of singlet oxygen degradation were obtained following the gel permeation chromatograms in the presence of an external standard. This procedure can not be used for alkali lignin considering its insolubility. In the case of steam exploded and organosolv lignins, the reactions follow zero order kinetics for the first 4–8 h; then, the reactions slow down and follow slower zero order kinetics. This behaviour can be explained assuming that easily degradable structures in the outer sphere of lignins are degraded in the first period, while the core lignin is degraded in the second one. The degradation in organosolv lignin is faster than in steam exploded lignin. Molecular weight distribution and the absence of guaiacyl units in steam exploded lignin can give rise to this behaviour. A similar behaviour was obtained performing singlet oxygen degradation on the pulp of steam exploded straw. Four-hour irradiation of steam exploded lignin from straw in the presence of singlet oxygen gave in low yield a lactone. A sample of lignin from pine was treated with singlet oxygen. Column chromatography of the residue showed the presence of six compounds: trans -sinapyl alcohol, 4-hydroxy-3,5-dimethoxybenzaldehyde, 4-hydroxy-3,5-dimethoxyphenylacetone, 4-hydroxy-3-methoxybenzaldehyde, cis -sinapyl alcohol, and sinapyl aldehyde. We obtained only compounds deriving from syringyl units in lignin in agreement with the hypothesis that guaiacyl units are more easily oxidable. The photochemical oxidation of lignin models in the presence of singlet oxygen was studied by using ab initio calculations. The treatment of the non-phenolic β- O -4 aryl ether derivatives (4-ethoxy-3-methoxy-2-(2-methoxyphenoxy)-acetophenone, 1-(4-ethoxy-3-methoxyphenyl)-2-(2-methoxyphenoxy)-3-hydroxy-1-propanone, 1-(4-hydroxy-3-methoxyphenyl)-2-(2-methoxyphenoxy)-3-hydroxy-1-propanol) gave products deriving from a formal β-C–O cleavage formation. The reaction occurred in low yields when a 2,6-dimethoxyphenol derivative is used. When the phenoxy part of the molecule showed a lower reactivity towards singlet oxygen (1-(4-hydroxy-3-methoxyphenyl)-2-(2,6-dimethoxyphenoxy)-3-hydroxy-1-propanol), the oxidation of the phenol moiety can occur. These results can be interpreted assuming a frontier orbitals control between the HOMO of the lignin model and the LUMO of singlet oxygen.

The convergent synthesis of the C12-C24 fragment (lower part) of macrolactin A is described. The adapted strategy allowed building up the lower moiety by the assembly of three key intermediates via organometallic addition. One hydroxylic stereogenic center was introduced by the application of chiral sulfoxides methodology on fragment C19-C24. The preparation of the versatile 1,3-anti diol synthon C12-C16 was achieved via opening of chiral epoxide and subsequent oxidation to a hydroxy ketone. Finally, reductive elimination of the appropriate allylic dibenzoate with Na/Hg introduced directly the C16-C19 (E,E)-diene unit, in a highly efficient stereoselective fashion.

Lignin powder, obtained from an abundant and low cost source, straw, through a low environmental impact process, the steam explosion, is used for the preparation of blends with low-density polyethylene (LDPE), linear low-density polyethylene (LLDPE), high-density polyethylene (HDPE) and atactic polystyrene (PS). The obtained blends are processable through the conventional techniques used for thermoplastics; the modulus slightly increases for most lignin-polymer blends, while the tensile stress and elongation reduce. Moreover, lignin acts as a stabilzer against the UV radiation for PS, LDPE and LLDPE.

The Smiles rearrangement was successfully applied to 4-hydroxybenzo[b]thiophene furnishing a facile entry to the 4-amino derivative. The rearrangement was extended to 5-methoxy-4-methoxycarbonyl[1]benzothieno[2,3-b]pyridine obtained via aza-Wittig/electrocyclization reaction of novel N-(4-methoxybenzothiophen-2-yl)iminomethyldiphenylphosphorane with methyl trans-4-oxo-2-pentenoate. The preparation of a novel 5-amino-4-methoxycarbonyl[1]benzothieno[2,3-b]pyridine, which is of interest as a potential secondary peptide structure mimic, was successfully achieved.

Peptidic aminopeptidase inhibitors, bestatin, phebestin and probestin have been prepared by stereo- and regiocontrolled reactions from a common α,β-epoxy ester precursor.

The synthesis of copolymers between lignin and electron poor alkenes is described. Lignin from steam-exploded pine, from steam-exploded straw, and organosolv were used as starting materials. Beforehand, lignins were fully characterized by using elemental analysis, ultraviolet spectroscopy, gel permeation chromatography (GPC), Fourier transform infrared (FTIR), and both1H and 13C nuclear magnetic resonance (NMR) spectroscopy. The synthesis of copolymers was performed using a previously described procedure utilizing calcium chloride and hydrogen peroxide as reagents. FTIR of copolymers showed absorptions due to the presence of both lignin and the electron withdrawing group on the alkene. GPC analysis showed the presence of fractions with high molecular weights: the Mz of lignin from pine was 3729 while the copolymer with methyl acrylate showed Mz = 383790. Differential calorimetry showed the presence of glass transitions in the range of −9 to 4.5°C due to the presence of grafted polyalkene chains. When acrylonitrile was used as starting material DSC analysis of the product showed a glass transition at 119°C, which can be attributed to grafted polyacrylonitrile chain. Lignin from steam explosion could be a good raw material in the preparation of graft copolymers. Furthermore, lignin from pine gave better results than that from straw. Finally, lignin from steam explosion gave better results than organosolv lignin. These results can be explained on the basis of the structural properties of used lignins. Both UV and 13C NMR spectra showed that lignin from pine contained a consistent amount of double bonds. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1163–1171, 2003

anti Ethyl β-thienyl-β-amino-α-hydroxy propionate was obtained regio- and diastereo-selectively in three steps and 45% overall yield, while 95% syn ethyl β-chloro-β-thienyl-α-hydroxy ester was obtained regio-selectively in two steps and 50% overall yield, both from 2-thienyl aldehyde.

Steam-exploded lignin from beech was obtained from a bench apparatus and fully characterized. The treatment of this lignin with hydrogen peroxide and ferrous sulfate (1.5, 5.8, 11.65, and 31.32 mmol of the reagent) induces an extensive degradation in the native lignin. The reaction was monitored using ultraviolet spectroscopy and the registered spectra showed that typical absorptions of lignin at 207, 230, and 276 nm disappeared. The analysis of the residue through gel permeation chromatography showed that lignin was extensively degraded. The treatment with 5.8 mmol of the reagent induced the formation of a trace of both polymeric material and small molecular weight degradation products. The treatment of recycled paper where 27% lignin was present gave extensive degradation of lignin.

The stereocontrolled synthesis of a C15C24 fragment of dolabelides is reported. The C19 and C21 hydroxyl-bearing stereocenters were installed using ruthenium-mediated asymmetric hydrogenations of cyclic hemiketal 4 and β-keto ester 7 . The C25C30 portion of dolabelides was prepared as well by ring opening of chiral epoxy alcohol 12 to set up the C27 stereogenic center.

A study on the addition of boron enolates of methyl ketones to trans α,β-epoxy aldehydes is reported. The reaction proceeds with an excellent anti stereoselectivity, consistent with the Felkin–Ahn model, toward the synthesis of hydroxylated compounds with defined stereochemistry.

Lignin obtained from steam explosion of pine was fully characterized. Elemental analysis, GPC, and ultraviolet and 1H and 13C NMR spectra revealed that the obtained lignin contains both guaiacyl and syringyl units. Lignin was dissolved in acetonitrile–ethanol and treated with visible light in the presence of both oxygen and Rose Bengal for different irradiation times. Column chromatography of the residue showed the presence of six compounds: trans-sinapyl alcohol, 4-hydroxy-3,5-dimethoxybenzaldehyde, 4-hydroxy-3,5-dimethoxyphenylacetone, 4-hydroxy-3-methoxybenzaldehyde, cis-sinapyl alcohol, and sinapyl aldehyde. The total amount of fine chemicals increases with the irradiation time. However, it increases rapidly during the first eight hours, but increases slowly after this period. The most important compounds obtained were sinapyl alcohol and 4-hydroxy-3,5-dimethoxybenzaldehyde, but sinapyl alcohol was obtained in the highest amounts after eight hours' irradiation, while the highest amounts of 4-hydroxy-3,5-dimethoxybenzaldehyde were obtained after irradiation for 4 h. After 48 h irradiation comparable amounts of sinapyl aldehyde were obtained. We obtained only compounds derived from the syringyl units in lignin in agreement with the hypothesis that the guaiacyl units are more easily oxidised.

A study of the organometallic addition to α,β-epoxy aldehydes in “non-chelation controlled” conditions is reported. The conditions able to give the best stereoselectivities are used to prepare the Abbott amino diol. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Novel N-(2-benzo[b]thienyl)iminophosphoranes react with α,β-unsaturated aldehydes and ketones to give benzo[b]thieno[2,3-b]pyridines in an aza-Wittig/electrocyclic-ring closure process. The diphenylmethyliminophosphorane reacts with aromatic and heteroaromatic aldehydes to give iminic products: upon UV irradiation, two imines furnish cyclization products in acceptable yields.

Opening of epoxides with LiAlH4, MgBr2·2OEt2 (solution in Et2O), MgBr2·OEt2 (suspension in Et2O), and NaBr/Amberlyst-15 has been studied. While 2-pyridyl epoxide 1 opens with complete regioselectivity, ortho-fluorophenyl epoxide 2 does not, but affords mixtures. Moreover, while the anti isomer (100−80%) is in all cases the major product with epoxide 1, epoxide 2 affords the anti isomer as major product with MgBr2 and the syn isomer as major product with NaBr/Amberlyst-15. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Four-hour irradiation of steam-exploded lignin from straw in the presence of singlet oxygen gave product showing high molecular weights. The only product obtained in low yield was the lactone 1. Irradiation of the same lignin sample for longer times allowed to obtain higher quantity of the same compound. The largest amount of the lactone was obtained after 24 h irradiation. This behaviour can be explained considering that lignin from straw can be easily oxidised by singlet oxygen and that 1 can be obtained from the singlet oxygen oxidation of 5–5′ units in the lignin.

New structurally simple indolic non peptidic HIV Protease inhibitors were synthesized from (S)- glycidol by regioselective methods. Following the concept of targeting the protein backbone, different substitution patterns were introduced onto the common stereodefined isopropanolamine core modifying the type of functional group on the indole, the position of the functional group on the indole and the type of the nitrogen containing group (sulfonamides or perhydroisoquinoline), alternatively. The systematic study on in vitro inhibition activity of such compounds confirmed the general beneficial effect of the 5-indolyl substituents in presence of arylsulfonamide moieties, which furnished activities in the micromolar range. Preliminary docking analysis allowed to identify several key features of the binding mode of such compounds to the protease.

‘One pot’ organometallic addition and subsequent ring opening of α,β-aziridine aldehydes is reported to afford anti–syn 3-bromo-1,2-amino alcohols in high chemical yield and stereoselectivity. The sequence allows the stereoselective preparation of syn 1,2-amino alcohols.

Biocatalytic resolution of the 7-benzyloxy-3,5- anti -dioxolan-1,3,5,7-tetrol and the 7-benzyloxy-3,5- syn -dioxolan-1,3,5,7-tetrol was found to be highly enantioselective leading to differently functionalized chiral tetrols with significantly high e.e.

The results obtained in the MgBr2-mediated opening of 2,3-bifunctionalized epoxides are reported. The studies showed that the chelation control of MgBr2 between different functionalities can in some cases be selective.

Selective ring opening and subsequent organometallic addition to α,β-epoxy aldehydes is found to afford anti-syn 3-bromo-1,2-diols in high stereo and chemical yield. This sequence is utilized for the enantioselective synthesis of (2S,3R,4R)-2-amino-1-cyclohexyl-6-methylheptane-3,4-diol (an isomer of the Abbott amino diol).

The novel N-(3-benzo[b]thienyl)iminophosphoranes 1b–d react with α,β-unsaturated aldehydes and ketones 2a–e to give varying mixtures of the regioisomeric benzothieno[3,2-b]pyridines 3a–d and 4a–d as a result of preferential attack of either imino nitrogen or α-thienyl carbon at the enone carbonyl group. The findings indicate that the progressive replacement of phenyl with methyl P-substituent greatly enhances the reactivity of the phosphorane 1 and concomitantly enhances the propensity of the phosphorane itself for addition to the enone by the α-thienyl carbon.

The steam exploded lignin from beech obtained with log R0 = 3.42 was characterized by using elemental analysis, UV, and NMR spectroscopy. The irradiation of this lignin in acetonitrile–ethanol 1 : 1 in the presence of both oxygen and Rose Bengal gave a residue that was chromatographed on silica gel and then analyzed through GC–MS. The analysis of the fractions showed the presence in the residue of small molecules deriving from lignin such as vanilline and sinapyl alcohol. Furthermore, palmitic acid and 2,5-dimethoxyhydroquinone were detected. Finally, some phenylalkanes, mainly deriving from tridecane, were detected in the last fraction deriving from the column chromatography.

The C(4–14) polyolic segment of antifungal macrolide strevertenes has been synthesized for the first time in protected form, incorporating four stereogenic centers. The synthetic strategy developed is based on the connection of two subunits prepared starting from the same chiral building block.

The lignins obtained from steam explosion of straw and beech at log R 0 3.94 and 4.45 were characterised. Elemental analysis, gel permeation chromatography, UV, 1 H and 13 C NMR spectra allow defining the characteristics of the lignins used. Pulps obtained from the steam explosion process were used as starting materials. The amount of lignin in the pulps was determined by using the Klason lignin determination. The lignins in pulp were irradiated with a visible light in the presence of Rose Bengal and oxygen in water suspension for 24 h. Extensive degradation of the lignin in the pulps was observed. In fact, the amount of lignin in the pulps dropped from 22–24% to 3–7%. The pulps from beech seem to be more sensitive to the process than that from straw. The same result was obtained by using cardboard. The irradiation with visible light of cardboard in water suspension with Rose Bengal in the presence of oxygen induced the reduction of the amount of lignin from 24% to 13%.

Chiral 3-substituted N-Boc-2,3-aziridino alcohols are opened in a regio and stereoselective fashion by MgBr 2 ; the obtained 3-bromo derivatives can be reduced and deprotected under mild conditions to the corresponding 1,2-amino alcohols.

Mild thermal reaction of indol-2-yl triphenyl- and methyldiphenyl-phosphorane derived from 2-azido-1-methylindole with enones provides a novel entry to 9-methyl-9H-pyrido[2,3-b]indoles through a tandem aza-Wittig-electrocyclization process.

By means of semi-empirical quantum-mechanical computations the minimum energy conformations of several β-substituted carbonyl compounds have been examined. On the basis of a unified model with different β-substituents, two of the possible six conformers are found to be the most probable as reactant-like transition state structures, in a non-chelating nucleophilic addition, offering the same π face of the carbonyl group. The applicability of a single model for tsuch reaction has been examined. The conformational models proposed well correlate the diastereoselection of the experimental reactions for most of the cases examined.

Regio and stereoselective opening of three membered rings by metal halides was utilized for the enantioselective synthesis of (2 S ,3 R )-3-amino-2-hydroxydecanoic acid and (3 R )-3-aminodecanoic acid.