Improved synthesis of the enantiomers of propafenone using chiral building blocks

Summary A short and efficient synthesis of the enantiomers of the antiarrhythmic drug propafenone (1) is described using both (R)-isopropylideneglycerol tosylate and (S)-glycidyl tosylate as chiral building blocks. The key step of the high yield synthesis is the acetalization of the carbonyl group in 1-(2-hydroxyphenyl)-3-phenyl-1-propanone (2) which allows application of mild reaction conditions in the subsequent alkylation of the phenolic hydroxy group.With our best wishes dedicated to Prof. Dr.H. Achenbach on the occasion of his 65^th birthday     

Asymmetric synthesis of both the enantiomers of trans-3-hydroxypipecolic acid

Both the enantiomers of trans-3-hydroxypipecolic acid have been synthesized employing the Sharpless asymmetric dihydroxylation and epoxidation as the key steps starting from a commercially available starting material 1,4-butanediol.     

Asymmetric synthesis of alkaloids using polyfunctionalized chiral building blocks

Enantiopure N‐sulfinyl‐δ‐amino‐β‐ketoesters and isoquinolones, prepared from sulfinimines (N‐sulfinyl imines) are a new class of polyfunctionalized chiral building blocks. These building blocks provide easy access to enantiomerically pure, functionalized piperidines and tetrahydroisoquinolines with a minimum of chemical manipulation and protecting‐group chemistry. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:486–492, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10090     

Asymmetric synthesis of both the enantiomers of antidepressant venlafaxine and its analogues

Chemoenzymatic asymmetric synthesis of antidepressant agent venlafaxine and its analogue have been reported in this communication. The main highlight of the reported synthesis is the stereoselective synthesis of cyanohydrins by (S)-hydroxynitrile lyase (Hevea brasiliensis) followed by lipase catalyzed kinetic resolution.     

Enantioselective synthesis of cis-1,2-dialkyl substituted cyclopentanoid and isoprostane building blocks via 6-exo-trigonal radical cyclizations

Two different 6-exo-trigonal cyclizations of enantiomerically enriched 6-heptenyl radicals readily afforded versatile synthetic precursors of cis-1,2-dialkyl substituted cyclopentane derivatives. Starting from one of these intermediates, we accomplished an enantiospecific formal synthesis of two important isoprostanes, namely 15-F_2c-IsoP and ent-15-F_2c-IsoP.     

Asymmetric hydrolysis of enol esters with two esterases from Marchantia polymorpha

Two esterases participating in the asymmetric hydrolysis of α-alkylated enol acetates to α-chiral ketones were isolated from the cultured cells of Marchantia polymorpha. These two esterases had opposite enantioselectivities and both of them reversed the stereoselectivity of protonation into the enol intermediate in the hydrolysis when the chain length and the bulkiness of α-substituents were increased.     

Efficient ytterbium triflate catalyzed microwave-assisted synthesis of 3-acylacrylic acid building blocks

The derivatives of 4-(hetero)aryl-4-oxobut-2-enoic acid are useful as building blocks in the synthesis of biologically active compounds. An efficient general protocol for the synthesis of these building blocks was developed. This method combines microwave assistance and ytterbium triflate catalyst and allows the fast preparation of the target acids starting from different (hetero)aromatic ketones and glyoxylic acid monohydrate giving pure products in 52-75% isolated yields.     

Asymmetric synthesis of suitably protected γ-hydroxy-aza-β3-homothreonine building blocks

An efficient and easily applicable method for the enantioselective synthesis of γ-Hydroxy aza-β³-homothreonine (aza-β³-Hyht) has been established. The method involves stereoselective reductive amination of glyoxylic acid and the corresponding Fmoc protected chiral hydrazine. A stereoselectivity of 99% was achieved for each step using (R)-2,3-O-isopropylideneglyceraldehyde as the chiral auxiliary. This new synthetic monomer is a useful building block for the solid-phase synthesis of new peptidomimetics.     

Asymmetric synthesis of serinol-monoesters catalyzed by amine transaminases

The asymmetric synthesis of serinol-derivatives was investigated employing different amine transaminases as biocatalysts. Under the optimized conditions conversions up to 92% and excellent enantiomeric excesses up to 99% ee were obtained providing access to both, the (R)- and (S)-configurations of the serinol-monoester (2-amino-3-hydroxypropyl hexanoate).     

Asymmetric synthesis of both enantiomers of syn-(3-trifluoromethyl)cysteine derivatives

The use of several chiral trifluoromethylated building blocks 1a, 1b, 9a and 9b was attempted to synthesize of syn-(3-trifluoromethyl)cysteine. A novel and efficient enantioselective synthesis of both enantiomers of syn-(3-trifluoromethyl)cysteine derivatives 12a and 12b was successfully achieved.     

Asymmetric synthesis of both enantiomers of anti-4,4,4-trifluorothreonine and 2-amino-4,4,4-trifluorobutanoic acid

A short and efficient enantioselective synthesis of both enantiomers of anti-4,4,4-trifluorothreonine and 2-amino-4,4,4-trifluorobutanoic acid was successfully developed. Trifluoromethylation of benzyl-protected bromoalkene 4 provided key intermediate trifluoromethylated trans-disubstituted alkene 2 in good yield. The sequence then involved Sharpless asymmetric dihydroxylation, nucleophilic opening of cyclic sulfate with NaN(3), palladium-catalyzed selective hydrogenation, and oxidation.     

Asymmetric synthesis of propargylic alcohols catalyzed by (−)-MITH

This investigation describes that in the presence of 2.5 mol % of (?)-2-exo-morpholinoisobornane-10-thiol (MITH) 1, catalytic asymmetric alkynylation of aldehydes gives enantioenriched propargylic alcohols with good enantioselectivities.     

Design and synthesis of macromolecular structures from self-assembling building blocks

The self-assembling properties of a variety of building-blocks are used to generate different types of nanostructures, e.g. molecular golfballs, molecular tubes, and molecular braids.     

Asymmetric synthesis of spiroketal, spiroether, and oxabicycle building blocks via stereoselective spiro- and bicycloannulation of 2-hydroxy dihydropyrans

A modular asymmetric synthesis of spiroketal, spiroether, and oxabicycle building blocks is described based on the spiro- and bicycloannulation of alpha-hydroxy dihydropyrans, which were obtained from sulfoximine-substituted homoallylic alcohols. Key steps of the syntheses are stereoselective Ferrier-type O- and C-glycosidation, ring-closing metathesis, and stereoselective Prins cyclization.     

Asymmetric synthesis by enzymatic hydrolysis of prochiral dienol diacetate.

Enzymatic hydrolysis of prochiral dienol diacetate 1 by Candida cylindracea lipase (C C L) leads to the keto enol acetate 2 in high yield with an enantiomeric excess> 98 %. The S configuration of the asymmetric center was assigned.     

Asymmetric synthesis of both enantiomers of α-methyl-α-methoxyphenylacetic acid from l-(+)-tartaric acid: formal enantioselective synthesis of insect pheromone (−)-frontalin

Both antipodes of α-methyl-α-methoxyarylacetic acid derivatives were prepared from a common chiralpool precursor l-(+)-tartaric acid. The key step involves the addition of Grignard reagents to 1,4-diketones derived from tartaric acid. The utility of this strategy was applied in the formal enantioselective synthesis of pine beetle pheromone (−)-frontalin.     

Total synthesis of both enantiomers of the macrocyclic lactone citreofuran

Both enantiomers of the polyketide-derived lactone citreofuran (4) have been prepared. The enantiopure building blocks were obtained on a chemoenzymatic route ((S)-6) and by a chiral pool synthesis ((R)-6). The crucial step in the synthesis, a macrolactonization, was accomplished under Mitsunobu conditions.     

Rapid synthesis of polyamide dendrimers from unprotected AB2 building blocks

A rapid synthetic method for the preparation of polyamide dendrimer without protection and deprotection steps has been developed. A symmetrically branched third-generation polyamide dendrimer was prepared by a convergent method involving activation of focal point with a condensing agent, diphenyl (2,3-dihydro-2-thioxo-3-benzoxazolyl)phosphonate (DBOP), followed by condensation of the active amide with the diaminocarboxylic acid 3,5-bis(4-aminophenoxy)benzoic acid as an AB2 building block.