Lipases-Promoted Enantioselective Syntheses of Monocyclic Natural Products

Abstract

This review is about using lipases as catalysts in organic synthesis. It provides some specific examples of stereoselective biotransformations used in our group to prepare non racemic chiral building blocks and the utilization of these intermediates to synthesize different target molecules by organic transformations.

Enantioselective Syntheses of the Proposed Structures of Kopeolin and Kopeolone

“…Initial disconnection reduced kopeolin (1) to intermediate 5 and to the commercially available umbelliferone. [8] As shown in Scheme 3, enone 11 was converted into enol ether 12 in 98 % yield by the 1,4-addition of lithium dimethyl cuprate in diethyl ether followed by quenching of the intermediate enolate with chlorotrimethylsilane (TMSCl) in the presence of hexamethylphosphoramide (HMPA) and N,N,N',N'-tetramethylethylenediamine (TMEDA). The latter would be prepared by Horner-Wadworth-Emmons (HWE) olefination from aldehyde 8.…”

Stereoselective Synthesis of Terpenoids through Lipase-Mediated Resolution Approaches

“…More in detail, enantioenriched acetates 93 [76] and 94 [77] were transformed in different γ-cyclogeraniol derivatives, which are synthetic precursors of a number of natural products, such as the marine terpenenes luffarin P (20) [26] and pallescensin-2 (98) [78]. Optically active alcohol 95 [79] was employed in the synthesis of many terpenes [10], of which the sesquiterpene (+)-dehydro-β-monocyclonerolidol (99) is reported as a representative example. Bicyclic esters 96 [80] and 97 [81] were used as starting compounds, to accomplish the first synthesis of the cytotoxic sesquiterpene (+)-glaucescenolide (100) and of the formal synthesis of the antitumor sesquiterpene (+)-confertin (101), respectively.…”

“…To this end, lipases have been successfully employed to catalyze the stereoselective hydrolysis or acylation of racemic starting materials, in order to accomplish the asymmetric synthesis of chiral building blocks. Since the stereoisomeric forms of a given compound usually show different biological activities, the industrial production of a number of active pharmaceutical ingredients (APIs), flavors, fragrances, natural products, and other bioactive chemicals [4][5][6][7][8][9][10][11][12] looks toward their stereoselective synthesis. In this context, the 'green' biocatalytic processes, and especially the approaches involving lipase-mediated resolution steps, have gained increasing relevance in the last forty years [13].…”

Optimization of the fermentation conditions and substrate specifity of mycelium-bound ester hydrolases of Aspergillus oryzae Cs007

“…Two typical and important classes of ester hydrolases are lipases (EC3.1.1.3, triacylglycerol hydrolases) and carboxylesterases (EC3.1.1.1, carboxyl ester hydrolases). 1,3,4,[7][8][9][10][11] Ester hydrolases widely exist in animals, plants and microorganisms. Furthermore, lipases prefer water-insoluble substrates, typically triglycerides composed of long-chain fatty acids, whereas carboxylesterases preferentially hydrolyze "simple" esters (e.g.…”