Synthesis of (4R,15R,16R,21S)- and (4R,15S,16S,21S)-rollicosin

A convergent synthesis of (4R,15R,16R,21S)-rollicosin (1) and (4R,15S,16S,21S)-rollicosin (2) was accomplished. Hydroxy lactone 6a and/or 6b were synthesized from 4-pentyn-1-ol, and α,β-unsaturated lactone 7 was synthesized from γ-lactone 8 and 5-hexen-1-ol. Inhibitory activity of these compounds was examined with bovine heart mitochondrial complex I.     

(2S,5R/2R,5S)-Aminoethylpipecolyl aepip-aegPNA chimera: synthesis and duplex/triplex stability

This article reports the design and facile synthesis of novel chiral six-membered PNA analogues (2S,5R/2R,5S)-1-(N-Boc-aminoethyl)-5-(thymin-1-yl)pipecolic acid, aepipPNA IV that upon incorporation into standard aegPNA sequences effected stabilization of complexes with complementary target DNA. Substitution of aegPNA unit by the designed monomer at the C-terminus was more effective than substitution at N-terminus. The stabilizing behaviour improved with degree of substitution and was found to be dependent on their relative positions in the sequence. The six-membered piperidine ring in the design may freeze the rigid chair conformations and the relative stereochemistry of the substituents may in effect direct the complex formation with DNA/RNA by sequence-specific nucleobase recognition. In the present aepipPNA analogues, the l-trans stereochemical disposition of the substituents seems to lead to the favorable pre-organization of the PNA oligomers for complex formation with DNA. The results reported here further expand the repertoire of cyclic PNA analogues.     

Biotransformation of (+)-(1R,2S)-fenchol by the larvae of common cutworm (Spodoptera litura)

Biotransformation of (+)-(1R,2S)-fenchol by the larvae of Spodoptera litura was carried out. Substrate was converted to three new terpenoids, (+)-(1R,2S)-10-hydroxyfenchol, (+)-(1R,2R,3S)-8-hydroxyfenchol and (−)-(1S,2S,6S)-6-exo-hydroxyfenchol, and one known terpenoid, (−)-(1R,2R,3R)-9-hydroxyfenchol. These structures were established by NMR, IR, specific rotation and mass spectral studies.     

Solvent-induced dual chirality switching in the optical resolution of tropic acid via diastereomeric salt formation with (1R,2S)-2-amino-1,2-diphenylethanol

Solvent-induced chirality switching in the optical resolution of racemic tropic acid (TA) with (1R,2S)-2-amino-1,2-diphenylethanol has been demonstrated. Recrystallization of the diastereomeric salt mixture from i-PrOH or EtOH afforded the (S)-TA salt, while the (R)-TA salt was deposited from 1,4-dioxane and water-enriched alcohol solutions. Dual chirality switching was achieved by using two different types of solvents. The X-ray crystal structures of both diastereomeric salts showed that incorporation of the crystallization solvent played a crucial role in stabilizing each diastereomeric salt crystal. The mechanism of chirality switching has been discussed on the basis of the relative stability of the salt, as deduced from their structures.     

Synthesis of (+)-(1S,2R) and (−)-(1R,2S)-2-aminocyclobutane-1-carboxylic acids

(+)-(1S,2R) and (−)-(1R,2S)-2-aminocyclobutane-1-carboxylic acids have been prepared in >97% ee and in 33% and 20% overall yields starting from a single, chiral, bicyclic compound perceived as a chiral uracil equivalent. Construction of the cyclobutane ring is achieved via a [2+2] photocycloaddition reaction of this chiral precursor with ethylene.     

Chemomicrobial synthesis of (R)- and (S)-lavandulol

(R)- and (S)-Lavandulol are important compounds in the cosmetics industry and in pheromone research. We have developed syntheses of (R)- and (S)-lavandulol from (S)- and (R)-limonene, respectively, by microbial Baeyer-Villiger oxidation of the intermediate unsaturated hydroxy ketone. It has been found that the same strain of Acremonium roseum can be successfully used in the key step of the synthesis of both enantiomers of lavandulol.     

Concise and practical synthesis of (2S,3R,4R,5R) and (2S,3R,4R,5S)-1,6-dideoxy-1,6-iminosugars

The syntheses of (2S,3R,4R,5R) and (2S,3R,4R,5S)-1,6-dideoxy-1,6 iminosugars 1a and 1b, respectively, from d-glucose are described. The key transformations in this reaction sequence include regio-selective epoxide ring opening with N-benzylamine followed by intramolecular reductive amination of amino-aldehyde.     

A new titanate/(+)-(1R,2S)-cis-1-amino-2-indanol system for the asymmetric synthesis of (S)-tenatoprazole

Tenatoprazole, a substituted imidazopyridinyl derivative, is an irreversible proton pump inhibitor (PPI), which is used for the prevention and treatment of gastric acid-related diseases. A new highly efficient asymmetric oxidation using cumene hydroperoxide (CHP) as the oxidant in the presence of titanium tetraisopropoxide (Ti(OiPr)₄) and (+)-(1R,2S)-cis-1-amino-2-indanol, in a polar aprotic solvent at 0-20 °C, has been developed to prepare tenatoprazole with an enantiomeric excess of >99%, a chemoselectivity of >90% and a chemical yield of >90% from the corresponding sulfide. This procedure was successfully implemented on scales ranging from 100 mg to multiple kilograms. Detailed studies of the parameters controlling purity and yield for this reaction are presented.     

Chiral separation of (R,S)-2-phenyl-1-propanol through cellulose acetate butyrate membranes

As the cellulose acetate butyrate possessed multichiral carbon atoms in its molecular structure unit, enantioselective membrane was prepared using cellulose acetate butyrate as membrane material. The flux and permselective properties of membrane using aqueous solutions of (R,S)-2-phenyl-1-propanol as feed solution was studied. The top surface and cross-section morphology of the resulting membranes were examined by scanning electron microscopy. When the membrane was prepared with 15 wt.% cellulose acetate butyrate and 20 wt.% DMF in the casting solution, and the operating pressure and feed concentration of racemate were 2 kgf/cm² and 5 mmol/L, respectively, over 98% of enantiomeric excess (e.e.) was obtained. This is a report, for the first time, that the cellulose acetate butyrate is used as optical resolution membrane material for isolating the optical isomers of (R,S)-2-phenyl-1-propanol.     

A concise synthesis of (2S,4R)- and (2S,4S)-4-methylglutamic acid

A concise, multi-gram scale method for producing the bioactive and enantiomerically pure epimers, (2S,4R)- and (2S,4S)-glutamic acids, in a single synthetic scheme is described.     

Aza variant of intramolecular nucleophile-catalyzed aldol lactonization (NCAL): formal synthesis of (3S,4R) and (3R,4S) 4-(hydroxymethyl)pyrrolidin-3-ol

Aza variant of intramolecular catalytic, asymmetric nucleophile-catalyzed, aldol lactonization (NCAL) reaction has been explored to synthesize β-lactone fused nitrogen heterocycles as aza sugars’ precursors by employing achiral amino acids. The utility of these bicyclic β-lactones is presented by the formal synthesis of aza sugars, (3S,4R) and (3R,4S) 4-(hydroxymethyl)pyrrolidin-3-ol.     

The stereoselective total synthesis of (+)-18-(6S,9R,10R)-bovidic acid

An expedient stereoselective total synthesis of 18-carbon (+)-(6S,9R,10R)-bovidic acid, isolated from the pelage and skin of a gaur B. frontalis is described using l-proline catalysed sequential α-aminoxylation and Horner-Wadsworth-Emmons olefination of aldehyde, cross metathesis and tandem Sharpless asymmetric dihydroxylation-S_N2 cyclization reaction as the key steps.     

Transformation of esters into allyl halides via substituted cyclopropanols. Application in the synthesis of (2S,3R,7R/S)-3,7-dimethyltridec-2-yl acetate and propionate, sex attractants of pine sawfly Diprion pini

A convenient new approach to the synthesis of the acetate and the propionate of (2S,3R,7R/S)-3,7-dimethyltridecan-2-ol, sex attractants of Diprion pini L., using the cyclopropanation of the ethoxycarbonyl group in O-THP protected ethyl (S)-lactate with ethylmagnesium bromide in the presence of titanium(IV) isopropoxide followed by C-2-C-3 cyclopropane ring opening as the key steps has been performed.     

Determination of the absolute configuration of the male aggregation pheromone, 2-methyl-6-(4′-methylenebicyclo[3.1.0]hexyl)hept-2-en-1-ol, of the stink bug Erysarcoris lewisi (Distant) as 2Z,6R,1′S,5′S by its synthesis

Lipase-catalyzed asymmetric acetylation of a mixture of (6R,1′S,4′S,5′R)- and (6R,1′R,4′R,5′S)-7′-norsesquisabinen-4′-ol (3) afforded a separable mixture of the recovered former and the acetate of the latter. The recovered alcohol was oxidized to (6R,1′S,5′R)-sesquisabina ketone (2), whose absolute configuration could be assigned by its CD comparison with (1R,5S)-sabina ketone (4). Conversion of (6R,1′S,5′R)-sesquisabina ketone (2) to the bioactive pheromone revealed the stereostructure of the male aggregation pheromone of the stink bug Erysarcoris lewisi (Distant) to be (2Z,6R,1′S,5′S)-2-methyl-6-(4′-methylenebicyclo[3.1.0]hexyl)hept-2-en-1-ol (sesquisabinen-1-ol, 1).     

An efficient synthesis of protected (2R,3R,4S)-4,7-diamino-2,3-dihydroxyheptanoic acid, a constituent of callipeltins A and D

An efficient and stereoselective synthesis of protected (2R,3R,4S)-4,7-diamino-2,3-dihydroxyheptanoic acid, a constituent of the depsipeptides, callipeltins A and D, from d-ribose is described.     

A total synthesis of (R,S)S-glucoraphanin

A total synthesis of (R,S)_S-glucoraphanin (GRP) has been completed by a novel, simple and convenient method in high overall yield (17% over seven steps). The study describes a method for the synthesis of natural and unnatural (methylsulfinyl)alkyl glucosinolates (GLs) and also opens useful pathways to synthesize GRP as well as other sulfinyl GLs.     

Formation of chiral 21-helical columnar host system with phenylacetylene unit by using (1R,2S)-2-amino-1,2-diphenylethanol

A tunable supramolecular phenylacetylene host system with a chiral channel-like cavity is developed by using (1R,2S)-2-amino-1,2-diphenylethanol. This host system possesses a chiral 2₁-helical columnar structure; chiral cavities are constructed by the self-assembly of the 2₁-helical column, and guest molecules are included by varying the packing of this column.     

Biomimetically inspired total synthesis of (12S)-12-hydroxymonocerin and (12R)-12-hydroxymonocerin

A concise asymmetric total synthesis of (12S)-12-hydroxymonocerin (1) and (12R)-12-hydroxymonocerin (2) were efficiently achieved from the known 4-bromo-2,6-dimethoxyphenol. The synthetic approach was inspired by our biomimetic synthesis of (+)-monocerin (3) and 7-O-demethylmonocerin (4). The cis-fused furobenzopyranones of 1 and 2 was efficiently constructed via an intramolecular nucleophilic trapping of a quinonemethide intermediate, which was obtained by benzylic oxidation of compound 10 using 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ).     

(1R,2R)-DPEN-derived triazolium salts for enantioselective oxodiene Diels-Alder reactions

Enantioselective oxodiene Diels-Alder reactions catalyzed by (1R,2R)-DPEN-derived triazolium salts were realized successfully. With 0.5 mol % of (1R,2R)-DPEN-derived triazolium salt C and 150 mol % of Et₃N, the reactions of various α-chloroaldehydes (α-bromoaldehyde) with substituted enones led to 3,4-dihydropyridinones and their derivatives in good yields, diastereoselectivities, and enantioselectivities (up to 97% ee).     

An efficient asymmetric synthesis of (S)-2-cyclohexyl-2-phenylglycolic acid, the acid segment of oxybutynin

An innovative and facile synthesis of the title compound has been developed starting from (R)-cyclohexylidene glyceraldehyde. The key step in the synthesis is a chiral template-driven Grignard addition with absolute diastereocontrol. The other attractive features are the operational simplicity and the use of inexpensive compounds/reagents.