Mandelic Esters Research Articles

Resolution of trans-2-azidocycloalkanols by separation of their mandelic acid esters

It is presented that resolution of (±)-trans-2-azidocylohexanol and (±)-trans-2-azidocyclooctanol can be effected with (R)-mandelic acid. (R)-Mandelate esters of these azido alcohols can be separated by column chromatography on silica gel in an efficient manner. Upon methanolysis (transesterification) of the diastereomerically pure (R)-mandelate esters by K2CO3, enantiomerically pure trans-2-azidocylohexanols and trans-2-azidocyclooctanols are obtained. Their synthetic relevance has been also demonstrated by subjecting them to some enantiospecific transformations, such as the Mitsunobu reaction and hydrogenolysis of the azide functionality. Notably, this is the first study reporting the preparation of enantiopure trans-2-azidocyclooctanols.

Synthesis of Optically Active N-(4-Hydroxynon-2-enyl)pyrrolidines: Key Building Blocks in the Total Synthesis of Streptomyces coelicolor Butanolide 5 (SCB-5) and Virginiae Butanolide A (VB-A)

AbstractStarting from 5-methylhexanal and (S)-configured N-propargylprolinol ethers, coupling delivered N-(4-hydroxynon-2-ynyl)prolinol derivatives as mixtures of C4 diastereomers. Resolution of the epimers succeeded after introduction of an (R)-mandelic ester derivative and subsequent HPLC separation. Alternatively, suitable oxidation gave the corresponding alkynyl ketone. Midland reagent controlled diastereoselective reduction afforded a defined configured propargyl alcohol with high selectivity. LiAlH4 reduction and Mosher analyses of the allyl alcohols enabled structure elucidation. The suitably protected products are used as key intermediates in enantioselective Streptomyces γ-butyrolactone signaling molecule total syntheses.

Modulating the properties of the lipase from Thermomyces lanuginosus immobilized on octyl agarose beads by altering the immobilization conditions

The lipase from Thermomyces lanuginosus (TLL) has been immobilized on octyl-agarose beads via interfacial activation under 16 different conditions (changing the immobilization pH, the ionic strength, the presence of additives like calcium, phosphate or glycerol) and using a low loading (1 mg/g support). Then, the properties of the different biocatalysts have been evaluated: stability at pH 7.0 and 70 °C and activity versus p-nitro phenyl propionate, triacetin and R- and S- methyl mandelate. Results clearly indicate that the immobilization conditions determine the final enzyme properties, altering enzyme stability (by 10 folds), activity (by 8 folds using R- methyl mandelate) and specificity (VR/VS changed from 0.7 to 2.3 using mandelate esters). For instance, the enzymes immobilized at pH 7.0 using 5 mM buffer were the most stable preparations, while the presence of 250 mM sodium phosphate greatly decreased the final enzyme stability. The biocatalyst stability of TLL increased with increasing NaCl in the immobilization buffer at pH 5. Fluorescence studies confirmed that the conformation of the different immobilized enzymes were different, despite being a physical and reversible immobilization method. Thus, the immobilization of TLL on octyl agarose beads under different conditions produced biocatalysts with different properties, the optimal condition depends on the studied reaction and condition.

Immobilization on octyl‐agarose beads and some catalytic features of commercial preparations of lipase a from Candida antarctica (Novocor ADL): Comparison with immobilized lipase B from Candida antarctica

Lipase A from Candida antarctica (CALA, commercialized as Novocor ADL) was immobilized on octyl-agarose, which is a very useful support for lipase immobilization, and coated with polyethylenimine to improve the stability. The performance was compared to that of the form B of the enzyme (CALB) immobilized on the same support, as both enzymes are among the most popular ones used in biocatalysis. CALA immobilization produced a significant increase in enzyme activity vs. p-nitrophenyl butyrate (pNPB) (by a factor of seven), and the coating with PEI did not have a significant effect on enzyme activity. CALB reduced its activity slightly after enzyme immobilization. Octyl-CALA was less stable than octyl-CALB at pH 9 and more stable at pH 5 and, more clearly, at pH 7. PEI coating only increased octyl-CALA stability at pH 9. In organic solvents, CALB had much better stability in methanol and was similarly stable in acetonitrile or dioxane. In these systems, the PEI coating of octyl-CALA permitted some stabilization. While octyl-CALA was more active vs. pNPB, octyl-CALB was much more active vs. mandelic esters or triacetin. Thus, depending on the specific reaction and the conditions, CALA or CALB may offer different advantages and drawbacks. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2735, 2019.

Immobilization of Eversa Lipase on Octyl Agarose Beads and Preliminary Characterization of Stability and Activity Features

Eversa is an enzyme recently launched by Novozymes to be used in a free form as biocatalyst in biodiesel production. This paper shows for first time the immobilization of Eversa (a commercial lipase) on octyl and aminated agarose beads and the comparison of the enzyme properties to those of the most used lipase, the isoform B from Candida antarctica (CALB) immobilized on octyl agarose beads. Immobilization on octyl and aminated supports of Eversa has not had a significant effect on enzyme activity versus p-nitrophenyl butyrate (pNPB) under standard conditions (pH 7), but immobilization on octyl agarose beads greatly enhanced the stability of the enzyme under all studied conditions, much more than immobilization on aminated support. Octyl-Eversa was much more stable than octyl-CALB at pH 9, but it was less stable at pH 5. In the presence of 90% acetonitrile or dioxane, octyl-Eversa maintained the activity (even increased the activity) after 45 days of incubation in a similar way to octyl-CALB, but in 90% of methanol, results are much worse, and octyl-CALB became much more stable than Eversa. Coating with PEI has not a clear effect on octyl-Eversa stability, although it affected enzyme specificity and activity response to the changes in the pH. Eversa immobilized octyl supports was more active than CALB versus triacetin or pNPB, but much less active versus methyl mandelate esters. On the other hand, Eversa specificity and response to changes in the medium were greatly modulated by the immobilization protocol or by the coating of the immobilized enzyme with PEI. Thus, Eversa may be a promising biocatalyst for many processes different to the biodiesel production and its properties may be greatly improved following a suitable immobilization protocol, and in some cases is more stable and active than CALB.

Cinchona-catalysed, Enantioselective Synthesis of β-Peroxycarboxylic Acids, β-Peroxyesters and β-Peroxyalcohols

A cinchona-catalysed, enantioselective oxa-Michael reaction of α,β-unsaturated aldehydes with either tert-butyl hydroperoxide or cumene hydroperoxide was developed. The reaction was optimised by screening of solvents, modification of the catalyst framework and variation of the acid co-catalysts. A strong relationship was noted between the pKa of the acid co-catalyst and the degree of selectivity. Enantioselective peroxidation of α,β- unsaturated aldehydes with tert-butyl hydroperoxide afforded β-peroxyaldehydes with good enantioselectivities. In situ oxidation of the latter compounds furnished β-peroxycarboxylic acids in high yields. Enantiomeric excesses were determined by derivitisation to their mandelate esters and subsequent separation by chiral high performance liquid chromatography. Peroxidation with cumene hydroperoxide was similarly successful with the products being isolated as stable β-peroxyalcohols. These latter β-peroxyalcohols offer a direct route to 5-membered, chiral cycloperoxides via a silver-mediated cyclisation. This reaction proceeds by trapping of the oxygen lone pair by the incipient carbocation followed by loss of the cumyl or tert-butyl group and formation of the cycloperoxide product. Keywords: Organocatalysis, cinchona, peroxidation, peroxyacids, peroxyesters, peroxyalcohols, cycloperoxides.

ChemInform Abstract: Kinetic Resolution of Mandelate Esters via Stereoselective Acylation Catalyzed by Lipase PS‐30.

Abstract By using lipase PS-30 as catalyst, the kinetic resolution of a series of racemic mandelate esters has been achieved via stereoselective acylation. The value of kinetic enantiomeric ratio (E) reached up to 197.5. Substituent effect is briefly discussed.

ChemInform Abstract: Concise Stereoselective Total Synthesis of Leiocarpin C.

A simple and highly concise strategy has been developed for the stereoselective total synthesis of leiocarpin C starting from commercially available mandelic ester. The strategy utilizes the OsO4-catalyzed cis-hydroxylation and selective reduction with K-Selectride as key steps.

Kinetic resolution of mandelate esters via stereoselective acylation catalyzed by lipase PS-30

By using lipase PS-30 as catalyst, the kinetic resolution of a series of racemic mandelate esters has been achieved via stereoselective acylation. The value of kinetic enantiomeric ratio (E) reached up to 197.5. Substituent effect is briefly discussed.

Concise Stereoselective Total Synthesis of Leiocarpin C

AbstractA simple and highly concise strategy has been developed for the stereoselective total synthesis of leiocarpin C starting from commercially available mandelic ester. The strategy utilizes the OsO4‐catalyzed cis‐hydroxylation and selective reduction with K‐Selectride as key steps.

Regio‐ and Diastereoselective CC Coupling of α‐Olefins and Styrenes to 3‐Hydroxy‐2‐oxindoles by Ru‐Catalyzed Hydrohydroxyalkylation

Regio‐ and Diastereoselective CC Coupling of α‐Olefins and Styrenes to 3‐Hydroxy‐2‐oxindoles by Ru‐Catalyzed Hydrohydroxyalkylation

Synthesis of the Aminocyclitol Units of (−)-Hygromycin A and Methoxyhygromycin from myo-Inositol

Concise and efficient syntheses of the aminocyclitol cores of hygromycin A (HMA) and methoxyhygromycin (MHM) have been achieved starting from readily available myo-inositol. Reductive cleavage of myo-inositol orthoformate to the corresponding 1,3-acetal, stereospecific introduction of the amino group via the azide, and resolution of a racemic cyclitol derivative as its diastereomeric mandelate esters are the key steps in the synthesis. Synthesis of the aminocyclitol core of hygromycin A involved chromatography in half of the total number of steps, and the aminocyclitol core of methoxyhygromycin involved only one chromatography.

Pd-Catalyzed Deoxygenation of Mandelate Esters

A new approach to the synthesis of phenylacetic acids and esters has been developed via the palladium-catalyzed deoxygenation of mandelate esters.

Suzuki–Miyaura Coupling Reaction of Boronic Acids and Ethyl Glyoxylate: Synthetic Access to Mandelate Derivatives

AbstractThe palladium‐catalyzed coupling reaction of arylboronicacids with ethyl glyoxylate provides a straightforward method for the synthesis of mandelic esters. Pd2(dba)3·CHCl3 in combination with 2‐di‐tert‐butylphosphanylbiphenyl as the catalytic system and Cs2CO3 as the base were used. The reaction tolerates a wide range of functionalized boronicacids. Mandelic esters were isolated in good‐to‐excellent yields with a variety of neutral, slightly electron‐rich, and slightly electron‐poor substituents.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Simple and Efficient Synthesis of Racemic Substituted Mandelic Acid Esters from Nonactivated Arenes and Ethyl Glyoxylate

Direct synthesis of racemic aromatic α-hydroxyacetic acid esters via Friedel-Crafts reaction of nonactivated, simple arenes with ethyl glyoxylate promoted by SnCl 4 or AlCl 3 is described. The use of SnCl 4 opens a fast access to various alkyl- and aryl-substituted mandelic acids esters at room temperature within two hours in good yield (>80%) and with high regioselectivity. The procedure was successfully employed also for the alkylation of compounds with condensed aromatic rings. Alternative hydroxyalkylations with AlCl 3 require longer reaction time and higher temperature to get a good yield.

Reversal of enantioselectivity in the hydroformylation of styrene with [2S,4S-BDPP]Pt(SnCl3)Cl at high temperature arises from a change in the enantioselective-determining step.

Deuterioformylation of styrene catalyzed by [(2S,4S)-BDPP]Pt(SnCl(3))Cl at 39 degrees C gave 3-phenylpropanal (3) and 2-phenylpropanal (2) (n:i = 1.8, 71% ee (S)-2) with deuterium only beta to the aldehyde carbonyl and in the formyl group. Small amounts of deuterium were also found in the internal (2.8%), cis terminal (1.4%), and trans terminal (1.3%) vinyl positions of the recovered styrene. Deuterioformylation of styrene at 98 degrees C gave 3- (3) and 2-phenylpropanal (2) (n:i = 2.3, 10% ee (R)-2) with deuterium both alpha and beta to the aldehyde carbonyl and in the formyl group. Deuterium was also found in the internal (20%), cis terminal (12%), and trans terminal (12%) vinyl positions of the recovered styrene. These deuterioformylation results establish that platinum hydride addition to styrene is largely irreversible at 39 degrees C but reversible at 98 degrees C. Hydroformylation of (E)- and (Z)-beta-deuteriostyrene at 40 degrees C, followed by oxidation of the aldehydes to acids, and subsequent derivitization to the (S)-mandelate esters confirmed that 84% of 2-phenylpropanal (2) arises from platinum hydride addition to the si-face of styrene, while 73% of 3-phenylpropanal (3) arises from platinum hydride addition to the re-face of styrene. At 100 degrees C, the effect of variable H(2) and CO pressure on n:i, % ee, and TOF of hydroformylation of styrene was investigated. The results are consistent with enantioselectivity not being fully determined until the final hydrogenolysis of a platinum acyl intermediate.

A General and Simple Synthesis of Phenylglyoxylic Esters via the Oxidation of Mandelic Esters with Ammonium Chlorochromate Adsorbed on Alumina

A general method for preparation of phenylglyoxylic esters by oxidation of mandelic esters with readily available ammonium chlorochromate adsorbed on alumina is described.

Chiral enol ethers in carbohydrate chemistry: De novo synthesis of protected L-2-deoxy hexoses

(3,4,6)Tri- and (3,4,)-di-O-benzyl-2-deoxy-L-glucose 8 and 12 have been de novo synthesized in a convergent seven-step sequence involving asymmtric endo heterocycloaddition of the new heterodiene, methyl (E)-benzyloxylmethylene pyruvate 2b with the O-vinyl mandelic ester (R)-(−)- 3.

Separation and structural studies of manganese(II), cobalt(II), nickel(II), copper(II) and cadmium(II) complexes of benzilic and mandelic esters

Solid metal complexes of benzilic and mandelic esters have been prepared and their structure elucidated using vis., i.r., n.m.r. and e.s.r. spectra. The results of elemental analysis are commensurate with the proposed formulae. Spectral studies indicate that the Ni complexes are octahedral, whereas the Co and Cu analogoues are distorted octahedral.

PLE catalyzed hydrolyses of α-substituted α-hydroxy esters: The influence of the substituents.

The enzymatic hydrolyses of a variety of α-substituted mandelic and lactic esters using pig liver esterase (PLE) have been investigated. High to moderate enantioselectivity was found for various α-substituted mandelic esters, whereas PLE showed low to no enantioselectivity for α-substituted lactic esters. We observed that the enantioselectivity of PLE depends strongly on the length and nature of the substituent at the α-position. Some consequences for an active site model of PLE are discussed.