Primary Ester Research Articles

Synthesis of novel vasodilatory active nicotinate esters with amino acid function

A variety of N-[(ethyl-4,6-diaryl-3-pyridinecarboxylate)-2-yl]amino acid esters 6a– h were synthesized through the reaction of 2-bromonicotinates 4 with a number of primary amino acid ester hydrochlorides 5 in refluxing tetrahydrofuran in the presence of triethylamine as dehydrohalogenating agent. Similarly, reaction of 4 with N-glycylglycine ethyl ester hydrochloride 7 ‘as a representative example of dipeptide derivative’ afforded smoothly the corresponding N-[(ethyl-4,6-diaryl-3-pyridinecarboxylate)-2-yl]- N′-glycylglycine ethyl ester analogues 8. However, reaction of 4 with 5 in refluxing pyridine yielded the unexpected 2-aminonicotinate esters 9. Vasodilation activity screening for the synthesized nicotinate esters was investigated in vitro on the contractile response of vascular thoracic aorta smooth muscle from Wistar rats, where all the tested compounds exhibit considerable vasodilatory properties. In addition, few prepared compounds especially, 6b, 6h and 9b reveal remarkable vasodilation potency (IC 50).

Scorpion digestive lipase: Kinetic study using monomolecular film technique

Using the classical emulsified system and the monomolecular film technique, we compared the interfacial properties of the scorpion digestive lipase (SDL) with those of higher animals’. In the absence of bile slats, SDL does not hydrolyse efficiently pure tributyrin, as well as dicaprin films maintained at low surface pressure. The preincubation of bile salts with tributyrin seems to be a better substrate for SDL than the pure tributyrin. A kinetic study on the surface pressure dependency, stereospecificity and regioselectivity of SDL was performed using monomolecular films of either three dicaprin isomers or three pairs of didecanoyl-deoxyamino- O-methyl glycerol enantiomers (DDG) containing a single hydrolysable decanoyl ester bond. With all diacylglycerol isomers, SDL has a surface pressure threshold of about 15 mN m −1, below which enzymatic activity is undetectable. SDL seems to prefer vicinal ester groups of the diacylglycerol isomers, with preference for sn-1 position at both 15 and 23 mN m −1. Furthermore, the maximum SDL activity is measured with DDG having a primary ester bond ( 1,3DDG, SII). This shows that SDL has a preference for the sn-1 position of this diacylglycerol analogue. Moreover, this was in line with the fact that SDL is inactive on sn-2 position of both DDG isomers and a triacylglycerol. With diacylglycerol analogue isomers, SDL shows a preference for distal isomers contrary to what has been observed with diacylglycerol isomers. SDL interacts with egg-phosphatidyl choline (egg-PC) monomolecular films. The critical surface pressure value (13 mN m −1) is comparable to those of pancreatic lipases.

Study of sulfonic acid esters from 1→4‐, 1→3‐, and 1→6‐linked polysaccharides

AbstractSulfonic acid esters of differently linked polysaccharides including cellulose, dextran, lichenan, and pullulan were synthesized homogeneously applying N,N‐dimethylacetamide/LiCl as the solvent. The dependence of the degree of substitution (DS) on the molar ratio of repeating unit to sulfonic acid chloride and on the structure of the reagent (benzene‐, p‐toluene‐, 4‐chlorobenzene‐, 2,4‐dinitrobenzene‐, 2,4,6‐trimethylbenzene‐, and 2,4,6‐triisopropylbenzene sulfonic acid chloride), as well as on the polysaccharide, was studied. DS values in the range of 0.2–2.3 were obtained. Bulky and electron withdrawing substituents on the aromatic ring inhibited ester formation. None of the sulfonic acid chlorides applied showed distinct regioselectivity. The polysaccharide sulfonic acid esters were soluble in organic solvents depending on the type of substituent and the degree of substitution. The molecular structure of the new polymers was confirmed by elemental analysis, FTIR, and 13C‐NMR spectroscopy. Subsequently, nucleophilic displacement reactions were carried out, which showed that the reactivity of the primary sulfonic acid ester group was higher than that of the secondary ones. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 2142–2150, 2006

248 Acid stable amylolytic enzymes and lipase as components of pancreatic enzyme replacement in Cystic Fibrosis

Difficulties of pancreas enzyme substitution are known in CF notwithstanding the intake of sometimes high doses. For the digestion in the duodenum, the acid gastric content must be brought by means of pancreatic bicarbonate to a considerably higher pH value, because the pH optimum of pancreatic enzymes is situated in the range between 6 and 9. In pancreatic insufficiency, shortage of bicarbonate impairs this neutralisation of pH. Postprandial duodenal pH may remain under a pH of 5 and can reduce the performance of the pancreatin therapy on several ways: (1) pancreas lipase and amylase are irreversibly inactivated at pH4; (2) bile salt precipitatin. (3) enzymes from pancreatin are too far from their respective pH optima; (4) enteric coated pancreatin may dissolve too late while the absorption of nutrients chiefly takes place in the first part of the duodenum-jejunum. Screening of a large variety of microorganisms resolved a source of Aspergillus niger amylase capable to resist acid treatment (pH 2.5, 37°C, 30 rain) and was selected for biochemical and clinical characterisation. The selection of an appropriate replacement of human lipases is not only to be focused on activity and stability in function of pH but also on a compatible isomeric specificity. Lipases from Aspergillus niger and Rhizopus javanicus were found to restrict lipolytic activity to primary ester linkages (similar to human pancreas lipase) and to be stable in a broad pH zone. Since the Aspergillus niger source was found to be lower in lipolytic activity compared to Rhizopus javanicus, the last was selected for further characterisation and clinical evaluation in function of therapeutic substitution in poor responders. 6. Gastroenterology

Selective deacetylation using iodine–methanol reagent in fully acetylated nucleosides

Selective deprotection of primary acetyl ester in nucleosides and carbohydrates using 1% iodine–methanol solution (w/v) was described and the mechanism was also discussed.

Biodegradable films of partly branched poly(l-lactide)-co-poly(epsilon-caprolactone) copolymer: modulation of phase morphology, plasticization properties and thermal depolymerization.

We report on the modulation of phase morphology, plasticization properties, and thermal stability of films of partly branched poly(l-lactide)-co-poly(epsilon-caprolactone) copolymer (PLLA-co-PCL) with additions of low molecular weight compounds, namely, triethyl citrate ester, diethyl phthalate, diepoxy polyether (poly(propylene glycol) diglycidyl ether), and with epoxidized soybean oil (ESO). The PLLA-co-PCL/polyether films showed significant stability against thermal depolymerization, high film flexibility, and good plasticizing properties, probably due to cross-linking and chain branching formation between diepoxy groups with both the end carboxyl and hydroxyl groups of the PLLA copolymer (initially present or generated during the degradation process) to produce primary ester and ether bonds, respectively. Diethyl phthalate and triethyl citrate ester were found to be efficient plasticizers for PLLA copolymer in terms of glass transition and mechanical properties, but the more water-soluble plasticizer triethyl citrate induced a dramatic loss in the molecular weight of the copolymer. Although ESO cannot play the role of a plasticizer, it substantially stabilizes and retards thermal depolymerization of the PLLA copolymer matrix, possibly because of a reaction between epoxy groups with the end carboxyl and hydroxyl groups of the PLLA copolymer. The presence of ESO in PLLA-co-PCL/ESO/triethyl citrate blends enhanced the compatibility and miscibility of the plasticizer with the PLLA copolymer matrix, considerably improved the mechanical properties (elongation at break), and substantially stabilized the copolymer against thermal depolymerization. It seems likely that the epoxy groups interact not only with the end hydroxyl and carboxyl group of the copolymer but as well with the hydroxyl group of triethyl citrate plasticizer to produce a new ether bond (C-O-C) as the cross-linking unit. On the other hand, for PLLA-co-PCL/ESO/polyether blends, (80/10/10) epoxidized oil distorts the compactness of the blend by diminishing the proposed entanglements between carboxyl, hydroxyl, and diepoxy groups of polyether and reduces the high elongation properties otherwise observed in the PLLA-co-PCL/polyether films. The multicomponent approach toward modulating poly(l-lactide)-co-poly(epsilon-caprolactone) copolymer films using epoxy compounds and plasticizers and the insight into the nature of various PLLA matrixes presented here offer advantages to a broad engineering of PLLA copolymer films having desirable physical properties and multiphase behavior for efficient uses in future technical applications.

Kinetic properties of turkey pancreatic lipase: A comparative study with emulsified tributyrin and monomolecular dicaprin

Using the classical emulsified system and the monomolecular film technique, we compared several interfacial properties of turkey pancreatic lipase (TPL) and human pancreatic lipase (HPL). TPL, like HPL, presented the interfacial activation phenomenon when vinyl ester was used as substrate. In the absence of colipase and bile salts, using tributyrin emulsion or monomolecular films of dicaprin at low surface pressure, TPL, unlike HPL, hydrolyzes pure tributyrin emulsion as well as dicaprin films maintained at low surface pressures. TPL was also able to hydrolyze triolein emulsion in the absence of any additive and despite the accumulation of long-chain free fatty acids at the interface. The difference of behaviors between TPL and HPL can be explained by the penetration power of each enzyme. The enzyme that presents the maximal pi(c) (TPL) interacts more efficiently with interfaces, and it is not denaturated at high interfacial energy. Turkey pancreatic lipase is more active on rac-dicaprin than HPL; a maximal ratio of 9 was found between the catalytic activities of the two lipases measured at their surface pressure optima (20 mN m(-1)). A kinetic study on the surface pressure dependency, stereospecificity, and regioselectivity of TPL was performed using enantiopure diglyceride (1,2-sn-dicaprin and 2,3-sn-dicaprin) and a prochiral isomer (1,3-dicaprin) that were spread as monomolecular films at the air-water interface. At low surface pressure (15 mN m(-1)), TPL acts preferentially on primary carboxylic ester groups of the diglyceride isomers (1,3-dicaprin), but at high surface pressure (23 mN m(-1)), this enzyme prefers both adjacent ester groups of the diglyceride isomers (1,2-sn-dicaprin and 2,3-sn-dicaprin). HPL prefers adjacent ester groups of the diglyceride isomers (1,2-sn-dicaprin and 2,3-sn-dicaprin). Furthermore, TPL was found to be markedly stereospecific for the sn-1 position of the 1,2-sn-enantiomer of dicaprin at low surface pressure (15 mN m(-1)), while at high surface pressure (23 mN m(-1)), this lipase presents a stereopreference for the sn-3 position of the 2,3-sn-enantiomer of dicaprin. HPL is stereospecific for the sn-1 position of the 1,2-sn-enantiomer of dicaprin both at 15 and 23 mN m(-1).

Safety assessment of polymeric additives for food packaging: Hydrolysis of polymeric plasticizers by digestive fluids

AbstractThe in vitro hydrolysis of poly(1,2‐propylene adipate) by digestive fluid liquids was studied to assess the safety of polymeric plasticizers that could migrate into food. A high extent of hydrolysis was obtained with freshly prepared intestinal fluid solutions. High performance size exclusion chromatography analysis indicated that the bulk plasticizer completely disappeared and that low molecular weight oligomers were formed within 4 h. Hydrolysis did not result in a significant conversion to the free monomers, like adipic acid, as was shown by gas‐phase chromatography. Measurements by NMR indicated that the cleavage selectively occurred at primary ester linkages. Fractionation of the hydrolysis products on silica gel gave six oligomeric fractions, which were recovered and analyzed. The absolute molecular weight of the plasticizers and the average molecular weight of the hydrolysis products were evaluated using proton NMR. Hydrolysis did not take place (<2%) under simulated gastric and saliva conditions. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 83: 956–966, 2002

Substrate specificity and effects of water-miscible solvents on the activity and stability of extracellular lipase from Streptomyces rimosus

Substrate specificity, regioselectivity and transesterification activity of purified extracellular lipase from Streptomyces rimosus were investigated. The enzyme showed pronounced lipolytic activity toward a number of triacylglycerols and oils of vegetable and animal origin. It hydrolyzed most efficiently medium chain length fatty acid glycerol esters (C8–C12). There was preference for the esters of C16 and C18 unsaturated fatty acids over C16 and C18 saturated fatty acid esters, as well as for triacylglycerol substrate with cis double bond (triolein) versus trans double bond (trielaidin). Streptomyces rimosus lipase hydrolyzed primary and secondary ester bonds in triacylglycerols (triolein and 2,3-dimercapto-1-propanol tributyrate). The lipase catalyzed the hydrolysis of poly(oxyethylene) sorbitan monoesters (Tween 20–80) with rate comparable for that determined with triacylglycerols and oils. Several water-miscible solvents enhanced the lipase activity. 1,4-Dioxane activated the enzyme in a broad concentration range, up to 4-fold. Lipase was stable in solvent mixtures containing 50% (v/v) ethanol, 1,4-dioxane, acetonitrile or acetone. Tetrahydrofuran and N,N-dimethylformamide (both 50%) inactivated the enzyme with t 1/2 of 5 min and t 1/2 of 2 h, respectively. Transesterification of racemic 1-phenyl ethanol with vinyl acetate, catalyzed by extracellular lipase from Streptomyces rimosus in n-hexane, proceeded with partial R-enantioselectivity.

Preparation of hyperbranched polymers by self-condensing vinyl radical polymerization

A novel acrylic AB * monomer, 2-(2-chloroacetyloxy)-ethyl acrylate (CAEA), was prepared from 2-hydroxyethyl acrylate with chloroacetyl chloride in the presence of triethylamine. The self-condensing vinyl polymerization of CAEA and CAEA with styrene catalyzed by the complex of CuCl/2,2 ′-bipyridyl has been studied. Hyperbranched polymers and copolymers containing ester groups in the main chain were prepared from radical polymerization. All the polymerization products were characterized by 1 H -NMR. It has been proved that CAEA exhibits distinctive polymerization behavior. During the initial stage of the polymerization, molecular weight of the polymer formed increases exponentially with polymerization time, and then the increase rate slows down. However, a significant amount of monomer remains present throughout the polymerization consistent with typical chain polymerization. Also, if a much longer polymerization time was used, the polymerization system became gel. As a result of the unequal reactivity of the primary ester halide and the secondary ester halide, the polymerization is different from an ideal self-condensing vinyl polymerization: the branch structures of polymers prepared depend dramatically on the ratio of 2,2 ′-bipyridyl to CAEA. Hyperbranched polymers and copolymers exhibit improved solubility in organic solvent. However, they have some lower thermal stability compared with their linear analogs.

Determining the regioselectivity of immobilized lipases in triacylglycerol acidolysis reactions

AbstractLipase regioselectivity is the ability to distinguish between primary (i.e., sn‐1,3) and secondary (sn‐2) ester functionalities in a triacylglycerol molecule, which is of importance in the manufacture of structured lipids. Unlike existing methods of assessment, which utilize hydrolysis reactions, an alternative technique to assess the regioselectivity of lipases in triacylglycerol transesterification reactions has been developed. An acidolysis reaction is performed between triolein and decanoic, lauric, or stearic acids under conditions that minimize acyl migration, and products are analyzed by silver‐ion complexation liquid chromatography, enabling detection of specific triacylglycerol positional isomers. From the rate of formation of these isomers the relative selectivity of the lipase for sn‐2 and sn‐1,3 ester bonds is determined. With lipases known to lack regioselectivity, the rate of reaction at sn‐2 was similar to that at sn‐1,3 from the start of the reaction. With sn‐1,3 selective lipases, the formation of triacylglycerol isomers with decanoic acid in the secondary position was not detected at any point in the reaction. Regioselectivity as a function of reaction progress was monitored. Two lipases from the genus Pseudomonas exhibited activity toward all positions, but the rate at sn‐2 was much reduced, and no incorporation of decanoic acid into this position was detectable until a high degree of conversion had been achieved.

Rapid esterification of nucleosides to solid-phase supports for oligonucleotide synthesis using uronium and phosphonium coupling reagents.

Nucleosides can be esterified to solid-phase supports using uronium or phosphonium coupling reagents and a coupling additive, such as 1-hydroxybenzotriazole (HOBT), 7-aza-1-hydroxybenzotriazole (HOAT), N-methylimidazole (NMI), or 4-(dimethylamino)pyridine (DMAP). However, DMAP was far superior to other additives and high nucleoside loadings (up to 60 micromol/g) and rapid coupling reactions (< or = 10 min) were possible. Hydroxyl-derivatized CPG was attached to nucleosides with 3'-succinyl or 3'-hydroquinone-O, O'-diacetic acid (HQDA or Q-Linker) carboxyl groups through a primary ester linkage. Alternatively, supports derivatized with succinic acid or the Q-Linker were attached directly to the 3'-OH group of nucleosides through a secondary ester linkage. Uronium reagents (HATU or HBTU) gave the best results with the HQDA linker arm, while the bromophosphonium (BrOP or PyBrOP) reagents were best with the succinyl linker arm. In all cases, the coupling reactions were much faster than previous methods using carbodiimide coupling reagents. The ease and speed of the reaction make this support derivatization procedure suitable for automated in situ couplings on DNA synthesizers.

Chemical Depolymerization Studies Of The Molecular Architecture Of Lime Fruit Cuticle

The chemical deprotecting reagent iodotrimethylsilane has been used to achieve controlled breakdown of ester bonds in cutin, an insoluble protective biopolymer obtained from the fruit of Citrus aurantifolia (limes). Four soluble products that preserve essential features of the cuticular molecular architecture have been isolated chromatographically and identified by multidimensional NMR and liquid secondary-ion mass spectrometry, whereas the insoluble residue has been characterized by solid state 13C NMR spectroscopy. The building blocks of the two dimers and one tetramer include the major Citrus cutin monomers 16-hydroxy-10-oxo-hexadecanoic acid and 10,16-dihydroxyhexadecanoic acid, which are joined by primary ester linkages. The CPMAS 13C NMR spectra of the unreacted residue implicate a heterogeneous reaction in which esters of primary alcohols within the cross-linked cutin network are preferentially cleaved. These studies offer a direct and definitive description of molecular connectivities within the protective polyesters of fruit cuticles.

Isolation and molecular structure of an oligomer produced enzymatically from the cuticle of lime fruit

The selective enzymatic cleavage of primary ester linkages with porcine pancreatic lipase has been used to investigate the structural framework of Citrus aurantifolia (lime) cutin, a cross-linked protective biopolymer obtained from the outer fruit skins. Among the soluble oligomeric products isolated from this reaction is a novel 1307-amu pentamer based on C 16 fatty acids and hydroxyfatty acids and assembled solely with linkages between the esters of secondary alcohols. This compound was isolated by high-performance preparative thin-layer chromatography, and a structure was proposed using evidence from electron-impact mass spectrometry supported by solution-state NMR spectroscopy. The building blocks of the pentamer include 10,16-dihydroxyhexadecanoic acid, hexadecanoic acid, 10-hydroxyhexadecanoic acid, and 1,7,16-trihydroxyhexadecanol, which can participate in polymer chain elongation as well as the formation of cross-link structures. Three of the four building blocks of the pentamer are among the major monomeric constituents of citrus cutins, but ω-hydroxyoxo acid monomers are absent from the soluble oligomers produced by enzymatic reaction. The resistance of fruit cutins to these breakdown procedures suggests that despite a predominance of primary ester linkages, a support network of secondary ester cross-links may limit the accessibility of interior ester bonds to the lipase enzyme. The selective enzymatic cleavage of primary ester linkages with porcine pancreatic lipase has been used to investigate the structural framework of Citrus aurantifolia (lime) cutin, a cross-linked protective biopolymer obtained from the outer fruit skins. Among the soluble oligomeric products isolated from this reaction is a novel 1307-amu pentamer based on C 16 fatty acids and hydroxyfatty acids and assembled solely with linkages between the esters of secondary alcohols.

Reworkable Epoxies: Thermosets with Thermally Cleavable Groups for Controlled Network Breakdown

A series of new cycloaliphatic epoxies were synthesized which have either secondary or tertiary ester bonds between cross-link sites. Thermal analysis data shows that the anhydride-cured epoxies with tertiary ester bonds can decompose at ∼220 °C, while those with primary ester links decompose at ∼340 °C. Dynamic mechanical analysis reveals that these new thermosets retain moduli comparable to the non-reworkable commercial thermosets with similar structure.

FACTORS THAT INFLUENCE VOLATILE ESTER BIOSYNTHESIS IN ‘DELICIOUS’ APPLES

We studied the influence of the intensity of light reaching fruit surfaces, cultivar, and maturity on amounts of the principal aroma and flavor volatiles (acetate esters) emitted from 'Delicious' apple fruits, and the relationship between anthocyanin accumulation and acetate ester emission. Light treatments of full sun (FS), 53% FS, 19% FS, and <1% FS were created by season-long bagging of 'Starkrimson' and 'Topred' fruit with shade cloth. Anthocyanin levels decreased with decreased light exposure, with 'Topred' fruits generally accumulating more anthocyanin than 'Starkrimson'. Contents of all flavonoid classes were also reduced as light level decreased. Volatile ester emissions were strongly affected by light exposure, with maxima occurring below 100% FS. Ester emission from 'Starkrimson' fruit at 179 days after full bloom (DAFB) was roughly twice that from 'Topred' in both years. The primary ester of both strains at all light exposures was 2-methyl butyl acetate, accounting for 50 to 75% of total ester content, with butyl and hexyl acetates as secondary components. Fruit position on the canopy also affected color and aroma/flavor of fruit. Western and southern aspect fruit generally emitted more esters than northern and eastern aspect fruit; anthocyanin accumulation was maximal in fruit from northern and eastern aspects. Differences in ester, anthocyanin, and flavonoid content due to light exposure were as seen in the main study. These data suggest that anthocyanin accumulation and volatile ester formation increase together with increasing light exposure, but at higher light exposures, continued increases in anthocyanin production come at the expense of acetate ester biosynthesis. For these strains, this happened between 53% FS and FS. Results suggest that 'Delicious' apples managed for maximum color have less volatile content and less potential for volatile development.

Model compound study for acrylic latex crosslinking reactions with cycloaliphatic epoxides

Cyclohexene oxide, methanol, and acetic acid were used as model compounds to study the competitive crosslinking of cycloaliphatic diepoxides with hydroxyl and carboxyl functionalized acrylic copolymers. Model reactions were performed as a function of molar ratio, pH, and temperature. At a 2:1:1 molar ratio of epoxide: hydroxyl: carboxyl, the formation of the primary ether and ester linkages were found to be the major crosslinking reactions. By increasing the molar ratio to 3:1:1, the formation of both the ether and ester oligomer products were significantly enhanced. As the pH of the media decreased, the rate of the crosslinking reactions increased, and generally ester products were formed preferentially to ether products. A temperature dependence of the rate of reactions were generally more pronounced at higher pH.

Modeling the catalytic activity and kinetics of lipase (glycerol-ester hydrolase)

In order to design industrial scale reactors and proceises for multi-phase biocatalytic reactions, it is essential to understand the mechanisms by which such systems operate. To illustrate how such mechanisms can be modeled, the hydrolysis of the primary ester groups of triglycerides to produce fatty acids and monoglycerides by lipase (glycerol-ester hydrolase) catalysis has been selected as an example of multiphase biocatalysis. Lipase is specific in its behavior such that it can act only on the hydrolyzed (or emulsified) part of the substrate. This follows because the active center of the enzyme is catalytically active only when the substrate contacts it in its hydrolyzed form. In other words, lipase acts only when it can shuttle back and forth between the emulsion phase and the water phase, presumably within an interphase or boundary layer between these two phases. In industrial applications lipase is employed as a fat splitting enzyme to remove fat stains from fabrics, in making cheese, to flavor milk products, and to degrade fats in waste products. Effective use of lipase in these processes requires a fundamental understanding of its kinetic behavior and interactions with substrates under various environmental conditions. Therefore, this study focuses on modeling and simulating the enzymatic activity of the lipase as a step towards the basic understanding of multi-phase biocatalysis processes.

Enzymatic synthesis of some Wax‐esters

AbstractThe Mucor miehei lipase, immobilized on a macroporous anion‐exchange resin (Lipozyme TM), was used to catalyze esterification and interesterification for the synthesis of wax‐esters. The first series of saturated esters, from 20 to 28 carbon atoms, were obtained with more than 80% yield. These esters are liquid up to 24 carbon atoms. Monounsaturated wax‐esters from 28 to 36 carbon atoms, were synthesized with yields greater than 70%. With few exceptions all these compounds are liquid up to 34 carbon atoms. Attempts of alcoholysis involving the ricinoleyl chain, revealed the remarkable selectivity of Lipozyme. Primary esters were found to be the sole reaction products (yields from 79 to 81,5%). It was possible to prepare diesters from octanediol and suberic acid with good yields (84–92%). Unfortunately yields were moderate in the synthesis of monoesters. 1,2‐alkanediol monolaurates were easily and selectively synthesized, but with a low yield. A fair amount of secondary ester was found besides the expected primary ester. A mechanism involving an equilibrium between both esters via a cyclic intermediate accounted for the acyl migration.

Imino Diels-Alder-Based Construction of a Piperidine A-Ring Unit for Total Synthesis of the Marine Hepatotoxin Cylindrospermopsin.

The synthesis of a piperidine A-ring precursor to the alkaloid cylindrospermopsin (1) is described. The initial approach to the A-ring precursor focused on the imino Diels-Alder reaction of diene 8 with ethyl (N-tosylimino)acetate (9) to form the cycloadduct 10 as a single stereoisomer. However, all attempts to convert ester 10 to a requisite diene such as 5 were unsuccessful. An alternative strategy involved the Diels-Alder cycloaddition of N-tosylimine 9 with oxygenated diene 19 under either thermal or Lewis acid-catalyzed conditions to produce a mixture of cis and trans enones 20 and 21. Although the undesired cis-enone 20 was the major product under all reaction conditions, it could be converted to the desired trans enone 21 by acid-catalyzed isomerization. Copper-mediated conjugate addition of vinylmagnesium bromide to cis-enone 20 followed by stereoselective ketone reduction with L-Selectride produced alcohol 23, whose structure was confirmed by X-ray crystallography. Similarly, trans-enone 21 was converted to alcohol 25 whose structure and stereochemistry were also established by X-ray analysis. Alcohol 25 was then protected as the silyl ether 26, which was hydroborated at the terminal olefin to produce primary alcohol ester 28having the stereochemistry and functionality needed for cylindrospermopsin.