Novel Chemoenzymatic Strategy for the Synthesis of Enantiomerically Pure Secondary Alcohols with Sterically Similar Substituents

Abstract

A novel chemoenzymatic strategy for the synthesis of enantiomerically pure secondary alcohols with sterically similar substituents is described. The key step is the kinetic lipase-catalyzed resolution of racemic mixtures of substituted propargylic alcohols. The efficiency of this new approach was tested in the preparation of the corresponding enantiomers of 1,11-hexadecandiol derivatives ((R)-5 and (S)-5). Two strategies were tested. In the first one, the racemic intermediate 1-octyn-3-ol (1) was resolved enzymatically and then elongated with 1-bromo-9,11-dioxadodecane. Alternatively, the racemic 1 can be elongated to the corresponding racemic 17,19-dioxa-7-eicosyn-6-ol (3) first and then resolved biocatalytically. Twelve commercially available lipases were screened for the kinetic resolution of these intermediates. Among them, Candida antarctica lipase (CAL-B) and Humicola lanuginosa lipase (HLL) were the best biocatalysts for the resolution of 1 (S enantiomer 90% ee, E = 35), and 3 (R enantiomer 90% ee, E = 34), respectively.

Lipase-catalysed selective monoacylation of 1,n-diols with vinyl acetate

“…The reactions were carried out in diisopropyl ether (DIPE) using the lipases immobilised onto a polypropylene support (Accurel EP100) as catalysts. 18 The progress of mono and diacetylated products was monitored by glc under the conditions described below.…”

Synthesis and Absolute Configuration of 6‐Hydroxylated New Ceramides in Human Skin, Ceramides B, 4, 7 and 8

“…90 % ee). [21][22][23] It must be added that asymmetric hydrolysis of the acetates of (±)-1-alkyn-3-ols with Bacillus subtilis esterase gave optically active acetates and alcohols of only mediocre enantiomeric purity. [24] Because substantical amounts of the enantiomers of 1-pentadecyn-3-ol (C = 18) were necessary to synthesize 1-4, we searched for a simple method which could afford both the enantiomers of 18 efficiently.…”

“…The alkynol (R)-18 was treated with 2.2 equiv. of n-butyllithium in THF to afford the corresponding dianion, to which was added (S)-Garner's aldehyde (21) at -40°C under argon. The product (4S,1ЈR,4ЈR)-22 was rather unstable to preclude chromatographic purification on silica gel.…”

Conformational Engineering of Lipases via Directed Immobilisation: Improving the Resolution of Chiral Drugs

“…For example, it was employed as optimum biocatalyst in the kinetic lipase-catalysed resolution of racemic intermediate, 1-octyn-3-ol, in organic solvents with high ee [74] in a novel chemoenzymatic strategy for the synthesis of enantiomerically pure secondary alcohols with sterically similar substituents (Scheme 3). Moreover, it has been employed in the deacetylation and oligomerisation of lactonic sophorolipids in isopropyl ether or toluene at high temperatures [75], as biocatalyst in the hydrolysis of the 5'-levulinate esters, furnishing 3'-Olevulinyl-2'-deoxynucleosides in >80% isolated yields [76].…”