Tetrahedron, asymmetry最新文献

Four novel isomers of norlignan glycoside were isolated from Cephalotaxus oliveri Mast.. Their structures were elucidated as 3S-4″-O-β-d-glucopyranosylnyasol 1, 3S-4′-O-β-d-glucopyranosylnyasol 2, 3S-4″-O-β-d-glucopyranosylhinokiresinol 3, 3S-4′-O-β-d-glucopyranosylhinokiresinol 4 by extensive spectroscopic methods including 1D and 2D NMR experiments (¹H, ¹³C, DEPT, ¹H–¹H COSY, HSQC, HMBC, ROESY) along with HR-ESIMS and comparison to literature data. Their absolute configurations were elucidated through CD spectra coupled with the quantum chemical CD calculations.

The enantiomers (up to 99% ee) of both geraniol- and nerol-derived 2-cyclohexyl-5,9-dimethyldeca-4,8-dienoic acid, the active ingredient of the wound healing medication Cygerol, were prepared via a low-temperature alkylation, basic hydrolysis, derivatization with (S)-4-benzyloxazolidin-2-one and chromatographic separation steps. The absolute configuration of stereocenters in the antipodes having an (E)- or (Z)-geometry of the internal double bond was determined based on characteristic ¹H NMR signals of the corresponding (S)-4-benzyloxazolidin-2-one-derived imides and on conversion to the known diethyl (S)-2-cyclohexylsuccinate and (S)-2-cyclohexylbutane-1,4-diol with reported specific rotations.

The asymmetric syntheses of the N-terminal α-hydroxy-β-amino acid components of microginins 612, 646 and 680 are reported. Conjugate addition of lithium (R)-N-benzyl-N-(α-methylbenzyl)amide to the requisite (E)-α,β-unsaturated ester followed by in situ enolate oxidation with (−)-(camphorsulfonyl)oxaziridne (CSO) gave the corresponding anti-α-hydroxy-β-amino esters. Sequential Swern oxidation followed by diastereoselective reduction gave the corresponding syn-α-hydroxy-β-amino esters. Subsequent N-debenzylation (i.e., hydrogenolysis for microginin 612, and NaBrO₃-mediated oxidative N-debenzylation for microginins 646 and 680) followed by acid catalysed ester hydrolysis gave the corresponding syn-α-hydroxy-β-amino acids, the N-terminal components of microginins 612, 646 and 680, in good yield. An analogous strategy for elaboration of the enantiopure anti-α-hydroxy-β-amino esters facilitated the asymmetric synthesis of the corresponding C(2)-epimeric α-hydroxy-β-amino acids.

Enantiomerically pure, chiral secondary and tertiary aziridine alcohols (including the aziridine analogue of ProPhenol—AziPhenol) have proven to be highly effective catalysts for enantioselective asymmetric reactions in the presence of zinc ions, including arylation of aromatic aldehydes, epoxidation of chalcone and addition of diethylzinc to aldehydes, leading to the desired chiral products in high chemical yields (up to 90%) and with ee’s up to 90%. A higher catalytic activity of Prophenol-type bis(aziridine alcohol) in the aforementioned asymmetric transformations has been demonstrated.

Racemic 1-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 1 and 1-methyl-1,2,3,4-tetrahydro-ß-carboline 3 were resolved through lipase-catalysed asymmetric acylation on the secondary amino group. High enantioselectivities (E >200) were observed when the acylation of racemic 1 was performed with phenyl allyl carbonate in the presence of Candida rugosa lipase in toluene at 40 °C or with Candida antarctica lipase B in tert-butyl methyl ether at 50 °C. Excellent enantioselectivity (E >200) characterised the CAL-B-catalysed acylation of racemic 3 with phenyl allyl carbonate in the presence of triethylamine in tert-butyl methyl ether at 50 °C. The product (R)-carbamates (ee >97%) were hydrolysed into the corresponding (R)-enantiomers of the free amines 1 and 3 (ee = 99%) with the use of Pd₂(dba)₃·CHCl₃ catalyst.

A simple and effective synthesis of enantiomerically pure 2-(N-aryl-, N-alkyl-aminomethyl)aziridines from (2S)-N-tritylaziridine-2-carboxylic acid methyl ester has been developed. Treating of this key ester with several primary and secondary amines in the presence of AlMe₃ provided the corresponding chiral N-trityl-2-carboxamides, and their reduction performed with different reagents resulted in the formation of the expected 2-(aminomethyl)aziridines. The choice of reaction conditions allows to either keep or leave the trityl substituent in the product. Such 2-(aminoalkyl)aziridines have shown very high catalytic efficiency in the asymmetric arylation of aldehydes and in other testing asymmetric reactions. On the other hand, homochiral N-trityl-2-carboxamides are interesting building blocks for the synthesis of various biologically active compounds.

In a route towards enantiomerically enriched 1-(β-hydroxypropyl)indoles, which are potentially useful building blocks for high value-added chemicals synthesis, a kinetic resolution approach by means of lipase-catalyzed enantioselective acylation as well as hydrolysis/methanolysis has been elaborated for the first time. The enzymatic resolution of chiral N-substituted indole-based sec-alcohols was successfully accomplished, yielding both enantiomeric forms of the employed derivatives with up to >99% enantiomeric purity via an enantioselective transesterification under mild reaction conditions. The most selective resolutions were obtained using fungal (CAL-B and TLL) and bacterial (PFL and BCL) lipases and vinyl acetate as the acyl group donor. The synthetic protocol described herein is very simple, user-friendly and efficient, thus paving the way for future access towards more complex compounds of this type. The absolute configurations of novel enantiomeric derivatives, and thus stereoselectivity of the described enzymatic reactions were confirmed by application of CDA-based NMR methodology and single-crystal X-ray diffraction analysis.