Enantioselective syntheses of (S)- and (R)-8,9-dihydroxydihydromagnolol

8,9-Dihydroxydihydromagnolol 5 was synthesized in four steps in which the synthesis of magnolol 4 was improved and the absolute configuration of 5 was confirmed as (R).     

Enantioselective synthesis of (10S)- and (10R)-methyl-anandamides

For the development of novel endocannabinoid templates with potential resistance to hydrolytic and oxidative metabolism, we are targeting the bis-allylic carbons of the arachidonoyl skeleton. Toward this end, we recently disclosed the synthesis and preliminary biological data for the (13S)-methyl-anandamide. We report now the total synthesis of the (10S)- and (10R)-methyl-counterparts. Our synthetic approach is stereospecific, efficient, and provides the analogs without the need for resolution. Peptide coupling, P-2 nickel partial hydrogenation, and cis-selective Wittig olefination are the key steps.     

Enantioselective synthesis of phosphonate analogues of (R)- and (S)-homoserine

The enantioselective synthesis of (R)- and (S)-1-amino-3-hydroxypropylphosphonic acid, the phosphonate analogues of (S)- and (R)-homoserine, has been accomplished in four steps and good overall yield starting from diethyl (3R,5R)- or (3S,5S)-5-(hydroxymethyl)-2-[(S)-1-phenylethyl]isoxazolidinyl-3-phosphonate, respectively.     

Enantioselective Hydrogenation over Chiral Cobalt Complexes with (+)-(1S,2S,5R)-Neomenthyldiphenylphosphine and (-)-(R,R)-2,2-Dimethyl-4,5-bis(diphenylphosphinomethyl)-1,3-dioxolane

The optical yield in enantioselective hydrogenation of methyl -acetamidocinnamate over mono- and diphosphine cobalt(II) complexes CoX₂L₂ [where X = Cl or CF₃SO₃, L = (+)-(1S,2S,5R)-neomenthyl-diphenylphosphine or L2' = (-)-(R,R)-2,2-dimethyl-4,5-bis(diphenylphosphinomethyl)-1,3-dioxolane], which are generated in situ, in the presence of sodium tetrahydridoborate increases with rise in the phosphine-to-metal ratio and hydrogen pressure. The maximal optical yields of (+)-(S)-N-acetylphenylalanine methyl ester attain 40% (CoX₂L₂) and 42% (CoX₂L₂').     

Enantioselective synthesis of (R)- and (S)-alpha-alkylcysteines via phase-transfer catalytic alkylation

We reported efficient enantioselective synthetic methodologies for (R)-alpha-alkylcysteines and (S)-alpha-alkylcysteines. The phase-transfer catalytic alkylation of 2-phenyl-2-thiazoline-4-carboxylic acid tert-butyl ester and 2-o-biphenyl-2-thiazoline-4-carboxylic acid tert-butyl ester, in the presence of chiral catalysts (1 or 2), gave the corresponding alkylated products, which could be hydrolyzed to provide (R)-alpha-alkylcysteines (67->99% ee) and (S)-alpha-alkylcysteines (66-88% ee), respectively.     

Enantioselective Preparation of (2R)- and (2S)-Azetidine-2-carboxylic Acids

The enantiomerically pure amino ketones 13 and 31 were prepared starting from the commercially available amino diol 9 and D -serine ( 21 ), respectively. Irradiation afforded highly functionalized azetidinols 15 and 33 in a fully stereoselective manner and in high yields, whereas N-phenacylglycine 5 gave only the secondary products of a Norrish-Type-II cleavage. Compounds 15 and 33 were converted into (2R)- and (2S)-azetidine-2-carboxylic acids 20 and 37 , respectively, in several steps. The influence of H-bonds on efficiency, chemo-, and stereoselectivity of the photochemical cyclization of 5 , 13 , and 31 was discussed. It was shown that conformational analysis of corresponding triplet biradicals is often valuable in understanding the photochemistry of amino ketones.     

Enantioselective synthesis of (2R,3R)- and (2S,3S)-2- [(3-chlorophenyl)-(2-methoxyphenoxy)methyl]morpholine

The enantioselective synthesis of the (R,R)- and (S,S)-enantiomers of 1 from commercially available 3-chlorocinnamic acid is reported. The Sharpless asymmetric epoxidation was used to establish the stereocenters in the synthesis of both enantiomers of 1.     

Enantioselective synthesis of (+)(R)- and (-)(S)-nicotine based on Ir-catalysed allylic amination

The synthesis of nicotine with enantiomeric excess of >99% ee was accomplished by asymmetric Ir-catalysed allylic amination followed by ring closing metathesis and racemization-free double bond reduction.     

Enantioselective syntheses of (13)C-labeled (2R)- and (2S)-phytochromobilin dimethyl ester

(2R)- and (2S)-phytochromobilin dimethyl ester have been prepared in enantiomerically pure form, specifically (13)C-labeled at C(10) or C(15).     

An Efficient Synthesis of Optically Pure (R)- and (S)-2-(aminomethyl)alanine ((R)- and (S)-ama) and (R)- and (S)-2-(aminomethyl)leucine ((R)- and (S)-aml)

An efficient synthesis of enantiomerically pure (R)- and (S)-2-(aminomethyl)alanine ((R)- and (S)-Ama) 1a and (R)- and (S)-2-(aminomethyl)leucine ((R)- and (S)-Aml) 1b is described (Schemes 1 and 2). Resolution of the racemic amino acids was achieved using L -phenylalanine cyclohexylamide ( 2 ) as chiral auxiliary. The free amino acids 1a, b were converted to the N^α-Boc,N^γ-Z-protected derivatives 11a, b (Scheme 3) ready for incorporation into peptides. Based on the three crystal structures of the diastereoisomeric peptides 8a, 8b , and 9b , the absolute configurations in both series were determined. β-Turn type-I geometries were observed for structures 8b and 9b , whereas 8a crystallized in an extended backbone conformation.     

Enantioselective synthesis of (R)- and (S)-curcumene and curcuphenol: an efficient chemoenzymatic route

An efficient enantioselective synthesis of curcumene and curcuphenol is described. The key intermediates, substituted butanoates 7a and 7b and their acids 8a and 8b are obtained in high enantiopurity (>99% ee) by a lipase-catalyzed kinetic resolution process. The enantiopure intermediates thus obtained were utilized for the total synthesis of the target compounds.     

Enantioselective drug monitoring of (R)- and (S)- propranolol in human plasma via derivatization with optically active (R,R)-O,O-diacetyl tartaric acid anhydride

A sensitive high-performance liquid chromatographic method was developed for the stereoselective assay of (R)- and (S)-propranolol in human plasma. The method involves diethyl ether extraction of the drugs and a racemic internal standard, N-tert.-butylpropranolol, followed by derivatization of the compounds with the chiral reagent (R,R)-O,O-diacetyl tartaric acid anhydride. The resulting diastereomeric derivatives were separated isocratically on a reversed-phase column. Quantitation was achieved by the peak-height ratio method with reference to the internal standard. The assay was accurate and reproducible in the concentration range 1-100 ng of (R)- and (S)-propranolol per ml plasma, using fluorescence detection at lambda ex 290 nm and lambda em 335 nm. The applicability of this method was demonstrated for the determination of concentration-time profiles of propranolol enantiomers in the course of comparative pharmacokinetic studies.     

Chemoenzymatic Synthesis of (R) - and (S) - Atenolol and Propranolol employing Lipase Catalyzed Enantioselective Esterification and Hydrolysis

Chemoenzymatic synthesis of (R) - and (S) - atenolol and propranolol employing lipase catalyzed enantioselective esterification and hydrolysis is described     

First Enantioselective Synthesis of (2R,3R)-and(2S,3S)-2-(4-hydroxyphenyl)-3-hydroxymethyl-1,4-benzodioxan-6-carbaldehyde

Numerous lignans containing 1,4-benzodioxane nucleus represent a class of natural products with cytotoxic and hepatoprotective activities1,2. Recently we have reported the racemic total synthesis of sinaiticin, a flavonolignan of the 1,4-benzodioxane type which was isolated from sinaiticum leaves found in sinai region of Egypt, using 2-(4-hydroxyphenyl)-3-hydroxymethyl-1,4-benzodioxan-6-carbaldehyde as the key interme-diate3,4. This species exhibits significant inhibitory activity against the …     

Enantioselective synthesis of (R)-(−)-praziquantel (PZQ)

Praziquantel 8 (2-cyclohexylcarbonyl-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinoline-4-one), a powerful anti-worm drug, has been synthesized in its enantiopure form via asymmetric transfer hydrogenation according to the Noyori protocol. Initially, the reduction of prochiral imine 4 afforded product 5 in 62% ee, but a single crystallization amplified the enantiomeric purity to 98% ee. The final (R)-(−)-praziquantel 8 was prepared in three subsequent steps in 56% chemical yield.     

Enantioselective synthesis of (S)-(+)-pantolactone

[reaction: see text] The Prins reaction of a chiral alkylidene morpholinone derived from (1R,2S)-ephedrine and 3-methyl-2-oxobutanoic acid proceeds with good diastereoselectivity to generate a spiro bis-acetal. Lewis acid mediated diastereoselective reductive cleavage of the spiro acetal and subsequent removal of the ephedrine portion generates a alpha-hydroxy-gamma-methoxy carboxamide which is readily converted to (S)-(+)-pantolactone with high enantiomeric excess.     

Ultrasound-promoted Lipase-catalyzed Enantioselective Transesterification of (R,S)-Glycidol

Enantioselective transesterification of glycidol with vinyl butyrate as an acyl donor was investigated in the presence of Bacillus subtilis lipase(BSL2) as catalyst. Comparison studies demonstrate the advantage of ultrasound over the conventional shaking for the enzymatic reaction in non-aqueous media. The effects of reaction conditions(ultrasound power, temperature, water activity and pH) on the activity and enantioselectivity were also investigated. Under the optimum conditions, the synthetic activity of BSL2 was 2.95 μmol·min?1·mg?1 and the enantioselectivity(E value) was 52.2. Compared with conventional shaking, ultrasound made the synthetic activity and the enantioselectivity increase 9.5-fold and 1.4-fold, respectively. Furthermore, the repeated use of BSL2 for five cycles resulted in no obvious loss of enzyme activity, suggesting that the enzyme is stable under low power ultrasound conditions.