Activated diesters

The enzymatic synthesis of polyesters from activated diesters was achieved under mild reaction conditions. The polymerization of bis(2,2,2-trichloroethyl) glutarate and 1,4-butanediol proceeded in the presence of PPL at room temperature in diethyl ether to produce the polyesters with molecular weight of 8.2 x 10. Vacuum was applied to shift the equilibrium forward by removal of the activated alcohol formed, leading to the production of high molecular weight polyesters. The polycondensation of bis(2,2,2-trifluoroethyl) sebacate and aliphatic diols took place using lipases BC, CR, MM, and PPL as catalyst in diphenyl ether. Under the... 

Based on nucleophilic addition, racemic allenyl sulfones were partially resolved by reaction with a deficiency of optically active primary or secondary amines [243]. The reversible nucleophilic addition of tertiary amines or phosphanes to acceptor-substituted allenes can lead to the inversion of the configuration of chiral allenes. For example, an optically active diester 177 with achiral groups R can undergo a racemization (Scheme 7.29). A 4 5 mixture of (M)- and (P)-177 with R = (-)-l-menthyl, obtained through synthesis of the allene from dimenthyl 1,3-acetonedicar-boxylate (cf. Scheme 7.18) [159], furnishes (M)-177 in high diastereomeric purity in 90% yield after repeated crystallization from pentane in the presence of catalytic amounts of triethylamine [158], Another example of a highly elegant epimerization of an optically active allene based on reversible nucleophilic addition was published by Marshall and Liao, who were successful in the transformation 179 — 180 [35], Recently, Lu et al. published a very informative review on the reactions of electron-deficient allenes under phosphane catalysis [244]. 

The enzyme also effects the aminolysis of non-activated diesters with diamines, e.g. equation 106337. 

As an extension of these studies on the use of sulfoximines in asymmetric reductions, BlNOL-derived phosphino sulfoximines of the 105 type were tested in both rhodium-catalyzed hydrogenations (yielding optically active diesters 104 or amino acid derivatives Scheme 2.1.1.35) and palladium-catalyzed allylic alkylations (not shown) in collaboration with Reetz and Gais [81, 82]. Here, enantioselectivities of up to >99 and 66% ee, respectively, were achieved. 

Russell et al. [43] studied lipase-catalyzed polymerizations of activated diesters and fluorinated diols. The effects of reaction time, continuous enzyme addition, enzyme concentration, and diol chain length were studied to determine factors that might limit chain growth. Potential limiting factors considered were enzyme inactivation, enzyme specificity, reaction thermodynamics, hydrolysis of activated esters and polymer precipitation. The polymer molecular weight at 50°C steadily increased and then leveled off after 30h at Mw 1773. 

This paper describes results of the polycondensation of active diesters with diamines in the presence of various polymer matrices which are expected to interact with monomers or the resulting polyamides owing to hydrogen bonding or charge-transfer, and the effect of irradiation on the charge-transfer polycondensation was investigated. 

The polycondensation reaction of active diesters with diamines was carried out in the presence of various matrices under various conditions. The amount of matrix was added according to the concentration based on the repeating unit. The reaction rates were followed by titrating the residual amine in the reaction mixtures or by determining the amount of liberated alcohol in the solutions by gas chromatographic analysis. After a given polycondensation time the solutions were poured into excess acetone, the mixtures were refluxed, and the precipitate was filtered, washed with acetone and excess water, and dried. To remove the matrices from the product, the precipitate was extracted with excess hot water or methanol for 24 hr by using a Soxhlet extractor. 

With regards to new polymeric biomaterial, Gomurashvilli and co-workers (2) have developed new biodegradable and tissue-resorbable co-poly(ester amides) (PEAs) using a versatile Active PolyCondensation (APC) method which involves di-p-toluenesulfonic acid salts of bis-(L-a-amino acid)-a,(o-alkylene diesters and active diesters of dicarboxylic acids as monomers. A wide range of... 

The PEAs reported in this work were prepared in a simple way by solution or interfacial polycondensation, where di-p-toluenesulfonic acid salts of bis-(a-amino acid)-a,co-alkylene diesters react with chlorides of dicarboxylic acids (interfacial polycondensation) or their active diesters (Active Polycondensation, APC). The APC method involves the condensation of two partners (I) bis-electrophilic, activated dicarboxylic acids, and (II) bis-nucleophilic, acid salts of bis-(a-amino acid)-a,(0-alkylene diesters in combination with di-p-toluenesulfonic acid salts of L-lysine benzyl ester. This reaction proceeds under mild conditions in common organic solvents and leads to polymer of high molecular weight (up to 300 KDa). A detailed review of the APC method has been recently summarized by Katsarava (7). 

It was expected that incorporation of less-toxic aromatic CPP fragments in the PEA backbone would increase mechanical strength, Tg and thermal stability, as well as decrease hydrophilicity. For these reasons an active diester of CPP was prepared according to Scheme 4 ... 

Perhaps the most extensively studied catalytic reaction in acpreous solutions is the metal-ion catalysed hydrolysis of carboxylate esters, phosphate esters , phosphate diesters, amides and nittiles". Inspired by hydrolytic metalloenzymes, a multitude of different metal-ion complexes have been prepared and analysed with respect to their hydrolytic activity. Unfortunately, the exact mechanism by which these complexes operate is not completely clarified. The most important role of the catalyst is coordination of a hydroxide ion that is acting as a nucleophile. The extent of activation of tire substrate througji coordination to the Lewis-acidic metal centre is still unclear and probably varies from one substrate to another. For monodentate substrates this interaction is not very efficient. Only a few quantitative studies have been published. Chan et al. reported an equilibrium constant for coordination of the amide carbonyl group of... 

Enzymatic acylation reactions offer considerable promise in the synthesis of specific ester derivatives of sucrose. For example, reaction of sucrose with an activated alkyl ester in /V, /V- dim ethyl form am i de in the presence of subtilisin gave 1 -0-butyrylsucrose, which on further treatment with an activated fatty acid ester in acetone in the presence of Hpase C. viscosum produced the 1, 6-diester derivative (71,72). 

The product is a mistuie of various polyoxyethylene chain lengths (29—31). Glycol diesters ate used as vinyl plasticizers the monoesters as surface-active agents and viscosity modifiers for alkyd resins (qv). 

PLE catalyzes the hydrolysis of a wide range of meso-diesters (Table 2). This reaction is interesting from both theoretical and practical standpoints. Indeed, the analysis of a large range of kinetic data provided sufficient information to create a detailed active site model of PLE (31). From a practical standpoint, selective hydrolysis of y j (9-cyclo-I,2-dicarboxylates leads to chiral synthons that are valuable intermediates for the synthesis of a variety of natural products. 

Oxo esters are accessible via the diastereoselective 1,4-addition of chiral lithium enamine 11 as Michael donor. The terr-butyl ester of L-valine reacts with a / -oxo ester to form a chiral enamine which on deprotonation with lithium diisopropylamide results in the highly chelated enolate 11. Subsequent 1,4-addition to 2-(arylmethylene) or 2-alkylidene-l,3-propanedioates at — 78 °C, followed by removal of the auxiliary by hydrolysis and decarboxylation of the Michael adducts, affords optically active -substituted <5-oxo esters232 (for a related synthesis of 1,5-diesters, see Section 1.5.2.4.2.2.1.). In the same manner, <5-oxo esters with contiguous quaternary and tertiary carbon centers with virtually complete induced (> 99%) and excellent simple diastereoselectivities (d.r. 93 7 to 99.5 0.5) may be obtained 233 234. 

The cyclopropane cyclizations by elimination of triflinic acid (CF3S02H) are readily effected by basic treatment of triflones (trifluoromethyl alkyl sulfones) with activated /-protons (equations 46 and 47)39. The cyclopropane diesters 45 are formed on treatment of 44 with potassium hydride in DMSO or sodium methoxide in methanol (equation 48). In contrast, the monoester 46 failed to give the desired cyclopropane40. Addition of carbanions derived from /f, y-unsaturated phenyl sulfones to a, /i-unsaturated carboxylic esters and subsequent elimination of benzenesulfinate ion give cyclopropanes possessing the unsaturated side chain and the ester function in trans positions (equation 49)41. 

These anionic surfactants are based on the petrochemically gained maleic acid anhydride. Sulfosuccinates are surface-active metal (mostly sodium) salts of either monoester or diesters of sulfosuccinic acid. 

This chapter will cover sulfosuccinate monoesters and diesters. The monoesters are best used in cosmetics and toiletries the diesters—especially those based on 2-ethylhexanol—play an important role in, for example, the textile industry due to their outstanding wetting activities [5]. Sulfosuccinamates and sulfosuccinamides are consumed in technical fields like emulsion polymerization. The next section discusses the historical development of the sulfosuccinates. 

Normally in the production of diesters great effort is spent in obtaining high yields. Catalytic support of the esterification reaction and azeotropic distillation to remove reaction water yields diesters near 100% purity. The amount of unreacted educt material is usually very small. Following sulfation, in the presence of a hydrotrope to reduce viscosity, a 65% active content product with virtually no byproducts is obtained. 

A divergent synthesis of tropane alkaloid ferruginine was reported by Node and coworkers [59]. The P-ketoester intermediate was prepared by a novel PLE-catalyzed asymmetric dealkoxycarbonylation (hydrolysis followed by a decarboxylation) of a symmetric tropinone-type diester (Figure 6.12). Dimethyl sulfoxide was added to the phosphate buffer pH 8 (1 9) to reduce the activity of PLE and prevent over-deal-koxycarbonylation leading to tropinone. 

Like similarly activated carboxylate esters, these aromatic phosphonate diesters 30 were readily hydrolyzed to GLYH3 in good yield and purity under typical strongly acidic or basic conditions, or in a stepwise fashion under extremely mild conditions via the zwitterionic monoaryl esters 32 (44). Products such as 32 or 33 readily precipitated after a few hours at room temperature from aqueous acetone. 

Other interesting examples of proteases that exhibit promiscuous behavior are proline dipeptidase from Alteromonas sp. JD6.5, whose original activity is to cleave a dipeptide bond with a prolyl residue at the carboxy terminus [121, 122] and aminopeptidase P (AMPP) from E. coli, which is a prohne-specific peptidase that catalyzes the hydrolysis of N-terminal peptide bonds containing a proline residue [123, 124]. Both enzymes exhibit phosphotriesterase activity. This means that they are capable of catalyzing the reaction that does not exist in nature. It is of particular importance, since they can hydrolyze unnatural substrates - triesters of phosphoric acid and diesters of phosphonic acids - such as organophosphorus pesticides or organophosphoms warfare agents (Scheme 5.25) [125]. 

Phosphotriesterase from P. diminuta (PTE) was found to exhibit high hydrolytic activity towards various types of tetracoordinated phosphorus acid esters. Apart from the phosphonothionate 92, phosphoric acid triesters 94 (Equation 45), °" benzenephosphonic acid diester 95 (Equation 46) ° and methyl-phenylphosphinic acid ester 96 (Equation 47) were also stereoselectively hydrolysed under kinetic resolution conditions. Of course, in the case of the latter three kinds of substrates, half of the reacting ester was irreversibly lost due to the formation of achiral phosphorus acids. 

Enzymatic synthesis of aliphatic polyesters was also achieved by the ringopening polymerization of cyclic diesters. Lactide was not enzymatically polymerized under mild reaction conditions however, poly(lacfic acid) with the molecular weight higher than 1 x 10" was formed using lipase BC as catalyst at higher temperatures (80-130°C). Protease (proteinase K) also induced the polymerization however, the catalytic activity was relatively low. 

PPF catalyzed an enantioselective polymerization of bis(2,2,2-trichloroethyl) tra 5-3,4-epoxyadipate with 1,4-butanediol in diethyl ether to give a highly optically active polyester (Scheme 9). °° The molar ratio of the diester to the diol was adjusted to 2 1 to produce the (-) polymer with enantiomeric purity of >96%. The polymerization of racemic bis(2-chloroethyl) 2,5-dibromoadipate with excess of 1,6-hexanediol using lipase A catalyst produced optically active trimer and pentamer. The polycondensation of 1,4-cyclohexanedimethanol with fumarate esters using PPL catalyst afforded moderate diastereoselectivity for the cis/trans monocondensate and markedly increased diastereoselectivity for the dicondensate product. 

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