Lipase succinic anhydride

Hog pancreas lipase Succinic anhydride Diethyl ether, room temp, 48 h E 12... 

Polymerization of oxiranes with succinic anhydride proceeded in the presence of PPL at 60 °C or 80 °C [63]. The ring-opening of the oxirane might proceed by a carboxylic acid catalyst, which is formed by the reaction of succinic anhydride with serine residue of the lipase catalyst. 

By screening a variety of lipases in organic solvent for their ability to acylate the racemic hydroxynitrile with succinic anhydride, Novozym 435 was found to yield the best results, affording product in 94-95 % ee at conversions of 47 9 % (Scheme 1.34). After optimization, the reaction was successfully run at 22 kg scale. The immobilized catalyst could be easily isolated by filtration and reused. 

S)-N-(tert-butoxycarbonyl)-hydroxymethylpiperidine (8) is a key intermediate in the synthesis of a potent tryptase inhibitor (Scheme 7.5). It was synthesized from (R,.S)-3-hydroxyrnethylpiperidine via fractional crystallization of the corresponding L(-)dibenzoyl tartrate salt followed by hydrolysis and acylation [17]. The lipase from Pseudomonas cepacia (PS-30) immobilized on polypropylene accurel PP catalyzed the esterification of racemic 6 with succinic anhydride and toluene, giving the (S)-hemisuccinate ester (7). This was easily separated and hydrolyzed by base to the (S)-Boc-protected 3-hydroxymethylpiperidine (8). Using this repeated esterification procedure gave a 32% yield (maximum theoretical yield = 50%) and 98.9% . 

Figure 57 Some of the biocatalytic steps using lipase developed at BASF Lipase-catalyzed kinetic resolution of a) phenyl ethanol 18 using succinic anhydride, b) Secondary amine 120 using ethyl methoxyacetate as acyl...

Polymerization of oxiranes with succinic anhydride proceeded in the presence of PPL catalyst.207 Under appropriate conditions, Mw reached 1 x 104. During the polymerization, the enzymatically formed acid group from the anhydride may open the oxirane ring to give a glycol, which is then reacted with the anhydride or acid by lipase catalysis, yielding polyesters. 

Bogel-Lukasik R, Lourenco NMT, Pedro V et al (2008) Lipase catalysed mono and diacylation of secondary alcohols with succinic anhydride in organic media and ionic liquids. Green Chem 10 243-248... 

As a typical procedure, crude lipase from Pseudomonas sp. (AK) (100 mg) was added to a mixture of flake guar (0.5 g) and succinic anhydride (0.2 g) in 2 mL of dimethylformamide (DMF) at 50°C, and the mixture was stirred for 24 h. The solid residue was washed three times with isopropanol and dried under vacuum to give 0.49 g of product in 98% yield. An IR spectrum of the product showed the presence of a strong ester bond at 1745 cm , whereas the spectrum of the control sample (without enzyme under the same conditions) gave the same band at 1745 cm but at much less intensity. 

Similar to this, Matsumura et al. [112] studied copolymerizations of succinic anhydride with oxiranes (glycidyl phenyl ether and benzyl glycidate). Copolymerization between succinic anhydride and glycidyl phenyl ether, using porcine pancreatic lipase as catalyst, in bulk reactions at 80 °C for 7 days resulted in a polyester in 80% yield (Mw = 4900 Mw/M = 2.4). 

Matsumura, S., Okamoto, T., Tsukada, K., and Toshima, K. (1998) Novel lipase-catalyzed ring-opening copolymerization of oxiranes and succinic anhydride forming polyesters bearing functional groups. Macromol. Rapid Commun., 19 (6), 295-298. 

Anhydrides. Ring-opening poly(addition-condensation) of cyclic acid anhydrides with glycols proceeded through lipase catalysis (135). The polymerization of succinic anhydride with 1,8-octanediol proceeded using lipase PF catalyst at room temperatime to produce the polyester with M of 3x 10 . 

KINETIC RESOLUTION OF A SECONDARY ALCOHOL (1-INDANOL) BY LIPASE-CATALYZED SUCCINYLATION WITH SUCCINIC ANHYDRIDE... 

To a flame-dried round bottom flask containing racemic 1 -indanol (2 mmol, 270 mg) dissolved in diethyl ether (10 mL) was added succinic anhydride (2 mmol, 200 mg a twofold excess since only one enantiomer reacts), followed by immobilized C. antarctica lipase B (Novozym 435, 300 mg can be reduced to 6 mg). The suspension was stirred at room temperature for 22-24 h to reach -50% conversion (44% in this example) as determined by HPLC of the mixture on a Chiralcel OD-H capillary column. The reaction was stopped by filtration to remove the immobilized enzyme that was washed with ethyl ether, dried at room temperature in air and saved for reuse up to seven times. The reaction rate decreases with subsequent uses, but the enantiose-lectivity remains high. The combined filtrates were extracted with aqueous sodium carbonate (1 M, 3 X 5 mL) and water (1x5 mL) to remove the succinate. The remaining ethyl ether solution containing unreacted 1 -indanol was concentrated by rotary evaporation and purified by chromatography on silica gel eluted with hexane/ethyl acetate 80 20 - 48% isolated )deld of (S)-l-indanol, 79% ee. Enantiomeric purity was measured after acetylation of the alcohol (Ac O, DMAP, NEt ) by HPLC on a Chiralcel OD-H capillary column. To recover the fast-reacting enantiomer, the combined aqueous extract (—20 mL) was extracted with ethyl ether (2x5 mL). Sodium hydroxide (2 g, 50 mmol) was added to the aqueous phase and stirred for 6 h at room temperature. The solution was extracted with dichloromethane (3X5 mL), the combined extracts washed with water (5 mL), dried over Na SO, concentrated by rotary evaporation and purified by silica gel chromatography 25% isolated yield (R)-l-indanol, >99% ee. 

M.S. Rasalkar, M.K. Potdar, M.M. Salunkhe, Pseudomonas cepacia lipase-catalysed resolution of racemic alcohols in ionic liquid using succinic anhydride role of triethylamine in enhancement of catalytic activity, J. Mol. Gatal. B Enzym. 27 (2004) 267-270. 

N. Bouzemi, H. Debbeche, L. Aribi-Zouioueche, J.-C. Fiaud, On the use of succinic anhydride as acylating agentfor practical resolution of aryl-alkyl alcohols through lipase-catalyzed acylation, Tetrahedron Lett. 45 (2004) 627-630. 

When an anhydride such as succinic anhydride is reacted with a racemic alcohol in organic solvent with a lipase, an enantioselective resolution can be achieved [89]. The enantioselective opening of racemic or meso cyclic anhydrides can constitute a good method for the preparation of nearly optically pure esters [90-93]. Examples of these reactions are depicted in Scheme 13. 

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