Methyl‐branched octanoic acids as substrates for lipase‐catalyzed reactions

Abstract

Hydrolyses of racemic methyl-branched octanoic acid thiolesters are described using six commercial lipases as catalysts. Branching at positions 2, 4 and 5 greatly reduced activity; branching at the 3-position virtually eliminated activity. The reactivities of the racemic branched thiolesters relative to the unbranched ester were very similar for each lipase preparation examined. In reactions involving configurationally pure 2-methyloctanoic acids, the S-enantiomer reacted faster both in esterification of aliphatic alcohols and in hydrolyses of aliphatic alcohol esters with all of the lipases examined. Stereobiases in hydrolyses of the octanoic acid esters branched at other positions were low and variable. In sharp contrast to the hydrolyses of the thiolesters of 2-methyloctanoic acid, two aryl esters of 2-methyloctanoic acid catalyzed by R. miehei lipase hydrolyzed with a bias for the R-configuration. A view of the ester-enzyme complex is offered to explain the relative rates of reaction of the racemic esters.

Autopoietic Self-Reproduction of Chiral Fatty Acid Vesicles

“…The enantiomeric excess of ( R )-(−)-2-methyldodecanoic acid ( 4(R) ) (99% e.e.) was determined via 1 H-NMR spectroscopy in the presence of Eu(hfc) 3 as chiral shift reagent, and confirmed through the conversion of compound 4(R) into the corresponding diastereoisomeric ( RR ) and ( RS ) amides 5 via reaction of its acyl chloride with enantiomerically pure α-phenylethylamine (see Experimental Section) . The overall process is highly stereoselective and its stereochemical course is in line with the formation of chelated ( Z )-enolate such as 6 (Scheme ), in the creation of a diastereofacial bias in the acylation reaction .…”

Lipase-catalyzed hydrolysis: effect of alcohol configuration on the stereobias for 2-methyloctanoic acid

“…The following enzyme preparations were employed (company, location, brand name, source, gift/purchase): Enzyme Development Co., New York, NY, Lipase R, Candida rugosa, purchase; Amano, Co., Troy, VA, GC-20, Geotrichum candidum, gift; Amano, Lipase P, Pseudomonas sp., gift; Tanabe Co., Marlborough, NJ, Rhizopus delemar, purchase; Gist-Brocades, Charlotte, NC, GB-S, Mucor miehei, gift; Amano, LPL, lipoprotein lipase, gift; Sigma Co., St. Louis, MO, porcine pancreatic lipase, purchase. These materials were employed directly; their protein content varied from 1.26 to 7.78% (Sonnet and Baillargeon, 1991). All organic solvents were of HPLC grade, roc-2,3-Isopropylidene glycerol (IPG) and the S-enantiomer were synthesized according to known procedures (Eibl, 1981), and (R)-and (S)-glycidol were purchased from Aldrich Chemical Co., Milwaukee, WI, and used directly; each is known to be 94-96% configurationally pure.…”

“…is critical to their industrial adoption. Pertinent to this are methods for resolving 2-methyl-substituted acids and their esters, compounds that are important naturally occurring flavor substances (Maarse and Visscher, 1987), but their reactivity with lipases is markedly reduced by the steric bulk of the substituent (Sonnet and Baillargeon, 1991).…”

Chemoenzymatic Synthesis of Nucleopeptides

“…This observation is in line with findings that lipases can not or can only just accommodate substrates in their active sites, which have a branching point in b position to the ester CO group. [18] Papain does not have this disadvantage, transformations proceed smoothly, yielding the desired selectively unmasked nucleoamino acids 11 and the phosphoamino acid 12 in much higher yield ( Table 1). The conditions of the enzymatic transformations are so mild that no undesired side reaction is observed; the acid-labile purine nucleosides remain intact, and a b elimination of the nucleotide, which readily occurs under weakly basic conditions (vide supra), does not occur.…”