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The aim of this study was to develop a drug eluting stent that prevents vein restenosis. For this, we selected argatroban as the study drug and poly(lactic acid) (PLA) as the matrix. To enhance the release of argatroban from PLA film, the addition of hydroxylesters (additives) was investigated. The additives investigated were diethyl tartrate (DET), diethyl malate (DEM), and triethyl citrate (TEC). Marked enhancement of drug release was observed in DET-added film, while TEC- or DEM-added film showed little enhancement. To clarify the effect of DET, the release profile based on the contents of the drug and DET in the film and the effect of alkyl chain length of tartrate were studied. Tartrates used were dimethyl, di-i-propyl, and di-n-butyl esters (DMT, DiPT, and DnBT, respectively), and the enhancement order was DMT ≅ DET ≫ DiPT ≅ DBT ≅ PLA alone. The reasons for enhancement were discussed from the viewpoint of drug release behavior, degradation of PLA, water uptake within the film, and SEM observations. It was concluded that enhancement of drug release was due to large amounts of water uptake within the film which resulted in the formation of open pores at its surface. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008

A convenient route to enantiopure azetidine-2,3-diones is described. The chiral ketene generated from commercially available L-(+)-diethyl tartrate on Staudinger cycloaddition with different imines gave spiro-P-lactams in good yields. These spiro-p-lactams were transformed into azetidine-2,3-diones in excellent yields in a two-step process.

In the present study, a less known polyester based on tartaric acid was characterized with respect to its degradation mechanism. Poly(2,3-(1,4-diethyl tartrate)-co-2,3-isopropyliden tartrate) (PTA) differs from commonly used biodegradable polyesters, such as poly(lactides-co-glycolides) (PLGA) by the presence of additional cleavable bonds in the polymer side chains. This modification results in different polymer properties and influences polymer degradation. The hydrolytic degradation of PTA was studied in parallel to PLGA using disc-shape matrices, which were obtained by compression-molding. The discs were incubated in pH 7.4 phosphate buffer solution at 37 degrees C. The degraded samples were characterized for percentage mass loss, water absorption, decay of molecular weight and change in glass transition temperature. The results demonstrate that the degradation of PTA proceeds via bulk erosion similar to PLGA. However, the degradation of PTA implants is characterized by a rapid mass loss within a short period of time appearing after a definite lag phase without remarkable mass loss. This makes the polymer promising for pulsatile drug release systems.

A novel synthetic approach has been devoleped to incorporate donor-acceptor substituted π-conjugated segments and chiral centres in main-chain polymeric systems. A series of optically active main-chain polyesters were synthesized by high-temperature polycondensation from biphenolic azo chromophores, (2R,3R)-(+)-diethyl tartrate, and terephthaloyl chloride. The biphenolic chromophores were bis(4-hydroxyphenylazo)-2,2′-dinitrodiphenylmethane and bis(4-hydroxyphenylazo)-2,2′-dinitrodiphenylsulfone. The effects of solvent, reaction time, and temperature on the polymerization were investigated. The optical activity of the polymers showed that the introduction of a substantial amount of chiral groups in the polymer chain leads to the formation of non-centric configurations. The chiral order was found to be thermally stable. The polyesters showed glass transition temperatures in the range 100–190°C and were thermally stable up to 350°C. All polyesters showed positive solvatochromism in UV–visible absorption spectra.

Nonlinearity in the diastereoselectivity of epoxidation of allylic alcohols with mixtures of titanium isopropoxide, tertbutyl hydroperoxide, and diethyl tartrate was observed. Racemic and enantiomerically pure alcohols E-2-methyl-4-hexen-3-ol and E-1-methoxy-5-(O-tertbutyldimethylsilyloxy)-2-penten-4-ol were prepared. Epoxidation reactions were carried out with Ti(OPri)4 and ButOOH accompanied by diethyl tartrate of varying enantiomeric purity. The simplest explanation of these results is that a dimeric epoxidation reagent is involved, with significantly different reactivity for the homochiral and racemic forms. Chirality 12:496–504, 2000. © 2000 Wiley-Liss, Inc.

The Simmons-Smith reaction starting from allylic alcohols using (R,R)-diethyl tartrate as a chiral auxiliary was found to proceed enantioselectively; i.e., the treatment of allylic allylic alcohols with diethylzinc and diethyl tartrate, followed by the reaction with diethylzinc and diiodomethane, afforded the corresponding cyclopropylmethyl alcohols in optically active form

A facile asymmetric synthesis of the D-myo-inositol derivative was achieved from diethyl 2,3-O- isopropylidene- d -tartrate in 7 steps. The two carboxylate groups of diethyl tartrate were converted simultaneously into dialdehyde to afford a key intermediate (1) for the synthesis of various protected D-myo-inositols.

Oxidation of aryl vinyl sulfides into aryl vinyl sulfoxides in the Bu1OOH−Ti(OPri)4−(R,R)-diethyl tartrate system was studied. The process afforded low optical yields (no more than 5%). A model of the oxidation was proposed that allows interpreting the dependence of the reaction enantioselectivity on the structure of a substrate.

A series of polymeric herbicides has been prepared by polycondensation of a range of diamines of different structures with diethyl tartrate derivatized with a conventional herbicide (2,4-dichlorophenoxy acetic acid and 2-methyl-4-chlorophenoxy acetic acid). The effects of hydrophilicity of the mainchain, and pH and the temperature of the aqueous environment on the rate of release of herbicides have been studied.

The Simmons-Smith reaction starting from allylic alcohols using (R,R)-diethyl tartrate as a chiral auxiliary was found to proceed enantioselectively; i.e., the treatment of allylic allylic alcohols with diethylzinc and diethyl tartrate, followed by the reaction with diethylzinc and diiodomethane, afforded the corresponding cyclopropylmethyl alcohols in optically active form

The reaction of secondary alcohols 1 with chlorodimethylsilane (HSiMe2Cl) proceeded in the presence of a catalytic amount of GaCl3/diethyl tartrate to give the corresponding organic chlorides 3. In the catalytic cycle, the reaction of diethyl tartrate 4a with HSiMe2Cl 2 gives the chlorosilyl ether 5 with generation of H2. Alcohol-exchange between the formed chlorosilyl ether 5 and the substrate alcohol 1 affords alkoxychlorosilane 6, which reacts with catalytic GaCl3 to give the chlorinated product 3. The moderate Lewis acidity of GaCl3 facilitates chlorination. Strong Lewis acids did not give product due to excessive affinity for the oxy-functionalities. Although tertiary alcohols were chlorinated by this system even in the absence of diethyl tartrate, certain alcohols that are less likely to give carbocationic species were effectively chlorinated using the GaCl3/diethyl tartrate system.

Structures of three dialkyl tartrates, namely, dimethyl tartrate, diethyl tartrate, and diisopropyl tartrate, in CCl4, dimethyl sulfoxide (DMSO)/DMSO-d6, and H2O/D2O solvents have been investigated using vibrational absorption (VA), vibrational circular dichroism (VCD), and optical rotatory dispersion (ORD). VA, VCD, and ORD spectra are found to be dependent on the solvent used. Density functional theory (DFT) calculations are used to interpret the experimental data in CCl4 and DMSO. The trans-COOR conformer with hydrogen bonding between the OH group and the C=O group attached to the same chiral carbon is dominant for dialkyl tartrates both in vacuum and in CCl4. The experimental VA, VCD, and ORD data of dialkyl-D-tartrates in CCl4 correlated well with those predicted for dimethyl-(S,S)-tartrate molecule as both isolated and solvated in CCl4. In DMSO solvent, dialkyl tartrate molecules favor formation of intermolecular hydrogen bonding with DMSO molecules. Clusters of dimethyl-(S,S)-tartrate, with one molecule of dimethyl-(S,S)-tartrate hydrogen bonded to two DMSO molecules, are used for the DFT calculations. A trans-COOR cluster and a trans-H cluster are needed to obtain a reasonable agreement between the predicted and experimental data of dimethyl tartrate in DMSO solvent. VA, VCD, and optical rotations are also measured for dialkyl tartrate-cyclodextrin complexes. It is noted that these properties are barely affected by complexation of dialkyl tartrates with cyclodextrins, indicating weak interaction between tartrates and cyclodextrin. Binding constants of alpha-CD and beta-CD with diethyl L-tartrate in both H2O and DMSO have been determined using isothermal titration calorimetry technique. The smaller binding constants (less than 100) confirmed the weak interaction between tartrates and cyclodextrin in the solution state.

Oxidation of aryl vinyl sulfides into aryl vinyl sulfoxides in the Bu1OOH−Ti(OPri)4−(R,R)-diethyl tartrate system was studied. The process afforded low optical yields (no more than 5%). A model of the oxidation was proposed that allows interpreting the dependence of the reaction enantioselectivity on the structure of a substrate.

A diastereomeric mixture at C-3 of panaxytriol (1) was synthesized starting from L-(+)-diethyl tartrate, and the absolute configurations at C-9 and C-10 of 1 were confirmed to be 9S and 10S, respectively. The absolute configuration at C-3 of 1 was reconfirmed to be R by the application of Mosher's method.

Chiral media for asymmetric solvent inductions. (S,S)-( + )-1,4-Bis(dimethylamino)-2,3-dimethoxybutane from (R,R)-( + )-diethyl tartrate intermediate: (R,R)-( + )-N,N,N′,N′-Tetramethyltartaric acid diamide reactant: 450 mL (7 mol) of liquid, anhydrous, cold (− 78°C) dimethylamine intermediate: (R,R)-( + )-2,3-Dimethoxy-N,N,N′,N′-tetramethylsuccinic acid diamide product: (S,S)-( + )-1,4-Bis (dimethylamino)-2,3-dimethoxybutane (DDB) reactant: (R,R)-( + )-diethyl tartrate reactant: (R,R)-( + )-tartaric acid (Firma Benckiser, D-Ludwigshafen, or Firma Boehringer, D-Ingelheim) Keywords: acylation; alkylation, O-alkylation; reduction, CONR2 CH2NR2; dimethylamine, recovered from 40% aqueous solution; tetrahydrofuran; dimethyl sulfate, poison

In 1986 Kagan, Agami et al.1 published a remarkable paper in the Journal of the American Chemical Society. The Freneh groups had studied asymmetric oxidation and aldol reactions* and they reported unique non-linear relationships between the enantiomerie excess (ee) of a chiral auxiliary and the ee of the product obtained in these reactions.1 In the titanium-mediated Sharpless epoxidation of geraniol (1) using diethyl tartrate (DET) as the ehiralligand (Seheme 2.1), the optieal purities of the epoxide (2) were signifieantly higher than the values calculated by assuming a linear relationship between tartrate and epoxide enantiomeric excesses (Figure 2.1, eurve b). In the asymmetric oxidation of methyl-p-tolyl sulfide (3) and in the proline-catalysed Robinson annulation of triketone (5) (Hajos-Parrish reaetion) (Seheme 2.1), negative deviations from linearity were observed (Figure 2.1, curve c).

The reaction of secondary alcohols 1 with chlorodimethylsilane (HSiMe(2)Cl) proceeded in the presence of a catalytic amount of GaCl(3)/diethyl tartrate to give the corresponding organic chlorides 3. In the catalytic cycle, the reaction of diethyl tartrate 4a with HSiMe(2)Cl 2 gives the chlorosilyl ether 5 with generation of H(2). Alcohol-exchange between the formed chlorosilyl ether 5 and the substrate alcohol 1 affords alkoxychlorosilane 6, which reacts with catalytic GaCl(3) to give the chlorinated product 3. The moderate Lewis acidity of GaCl(3) facilitates chlorination. Strong Lewis acids did not give product due to excessive affinity for the oxy-functionalities. Although tertiary alcohols were chlorinated by this system even in the absence of diethyl tartrate, certain alcohols that are less likely to give carbocationic species were effectively chlorinated using the GaCl(3)/diethyl tartrate system.

A facile asymmetric synthesis of the D-myo-inositol derivative was achieved from diethyl 2,3-O- isopropylidene- d -tartrate in 7 steps. The two carboxylate groups of diethyl tartrate were converted simultaneously into dialdehyde to afford a key intermediate (1) for the synthesis of various protected D-myo-inositols.

The reaction of dillyltin dibromide, readily prepared from allyl bromide and tin powder, with aldehydes in the presence of monosodium-(+)-diethyl tartrate affords the corresponding homoallylic alcohols in good yields with enantiomeric excesses in the range 42 to 71%.

The induced circular dichroism (CD) spectra of 21 achiral or racemic cobalt(III) complexes have been measured in a chiral medium containing (+)589-diethyl tartrate in the region of the first d-d transition bands. The absolute value of the molar circular dichroism (Δe) observed for these complexes is in the range of about 0.04–0.3 cm−1 mol−1 dm3. The induced CD spectra of the racemic complexes show a different pattern from the natural CD spectra of their resolved enantiomers. The observed induced CD spectra have been discussed in relation to the stereochemistry of the complexes.

The reaction of dillyltin dibromide, readily prepared from allyl bromide and tin powder, with aldehydes in the presence of monosodium-(+)-diethyl tartrate affords the corresponding homoallylic alcohols in good yields with enantiomeric excesses in the range 42 to 71%.

A quite simple procedure to synthesize optically active secondary homoallylic alcohols from the reaction between aldehydes and allylic tin(IV) complexes containing (+)-diethyl tartrate as chiral auxiliary ligand is reported.