Asymmetric synthesis of (−)-(S,S)-homaline

The asymmetric synthesis of (−)-(S,S)-homaline was achieved in 8 steps from commercially available starting materials using the diastereoselective conjugate addition of the novel lithium amide reagent lithium (R)-N-(3-chloropropyl)-N-(α-methyl-p-methoxybenzyl)amide to methyl cinnamate to install the correct stereochemistry. Subsequent functional group manipulation of the resultant β-amino ester and Sb(OEt)₃-mediated macrolactamisation was followed by homodimerisation to give (−)-(S,S)-homaline in 18% overall yield, representing the first asymmetric, and by far the most efficient synthesis of this natural product reported to date.     

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.     

Stereoselective synthesis of tetrahydroisoquinoline alkaloids: (−)-trolline, (+)-crispin A, (+)-oleracein E

Tetrahydroisoquinoline alkaloids, (S)-(−)-trolline, (R)-(+)-crispin A, and (R)-(+)-oleracein E, have been synthesized stereoselectively from the both enantiomers of common intermediate (S)-4 and (R)-4. The key step in the synthesis include a stereoselective Bi(OTf)₃-catalyzed intramolecular 1,3-chirality transfer reaction of chiral non-racemic amino allylic alcohols (S)-6 and (R)-6 to construct both enantiomers of (E)-1-propenyl tetrahydroisoquinoline 4.     

A concise enantioselective synthesis of l-(−)-733,061 and (2S,3S)-methyl 3-aminopiperidine-2-carboxylate using catalytic enantioselective aza-Henry reaction as key step

An efficient enantioselective synthesis of l-(−)-733,061 and (2S,3S)-methyl 3-aminopiperidine-2-carboxylate is accomplished by means of catalytic enantioselective aza-Henry reaction. A key feature of this protocol is organocatalysis as genesis of chirality to ensure high degree of distereo- and enantiocontrol.     

Synthesis and odor of optically active trans-2,2,6-trimethylcyclohexyl methyl ketones and their related compounds

The synthesis characterized by cationic olefin cyclizations accomplished using ketone enol esters and odor of novel (1R,6S)- and (1S,6R)-2,2,6-trimethylcyclohexyl methyl ketones (5) are described. The stereoselective syntheses of (E)-(1R,6S)- and (E)-(1S,6R)-1-(2,2,6-trimethylcyclohexyl)-2-buten-1-one (6) and (1R,6S)-ethyl 2,2,6-trimethylcyclohexylcarboxylate (7), useful raw materials for flavor and fragrance, starting from the (1R,6S)- and (1S,6R)-5 are also described.     

A convenient and efficient synthesis of (S)-lysine and (S)-arginine homologues via olefin cross-metathesis

A convenient five step synthesis of (S)-homolysine, incorporating a key olefin cross-metathesis step in the chain extension methodology, has been developed, together with a six step related synthesis of a new homologue of arginine, (S)-bishomoarginine.     

The substrate specificity of the heat-stable stereospecific amidase from Klebsiella oxytoca

The substrate specificity of the heat-stable stereospecific amidase from Klebsiella oxytoca was investigated. In addition to the original substrate, 3,3,3-trifluoro-2-hydroxy-2-methylpropanamide, the amidase accepted 2-hydroxy-2-(trifluoromethyl)-butanamide and 3,3,3-trifluoro-2-amino-2-methylpropanamide as substrates. Compounds with larger side chains and compounds where the hydroxyl group was substituted with a methoxy group, or in which the CF₃ group was substituted by CCl₃, were not accepted. The biotransformation is a new synthetic route to (R)-(+)-3,3,3-trifluoro-2-amino-2-methylpropanoic acid, and its related (S)-(−)-amide, and to (R)-(+)-2-hydroxy-2-(trifluoromethyl)-butanoic acid and its related (S)-(−)-amide.     

Synthesis and regioselective substitution of C-6 alkoxy derivatives of (S)-nicotine

Enantiopure (S)-6-alkoxynicotine derivatives have been synthesized in two steps from (S)-nicotine via (S)-6-iodonicotine. Deprotonation and substitution at the C-5 position of the pyridine ring of (S)-6-methoxynicotine were achieved using mesityllithium as the base at 0 °C. Conditions for the C-4 lithiation/substitution of (S)-6-isopropoxynicotine and (S)-5-chloro-6-methoxynicotine were also developed.     

Stereoselective synthesis of (−)-tetrahydrolipstatin via a radical cyclization based strategy

An efficient and flexible approach for the total synthesis of (−)-tetrahydrolipstatin is described. The main features of the synthetic strategy are a stereocontrolled radical cyclization and the successful utilization of commercially available S-malic acid.     

Synthesis of (S)-2-amino-7-methoxytetralin and isoindolo[1,2-a]isoquinolinone derivatives from l-aspartic acid

This paper describes a new total synthesis for (S)-2-amino-7-methoxytetralin, (S)-7-MeO-AT, from l-aspartic acid in an overall yield of 10% over nine steps. The major loss was ascribed to a key intramolecular Friedel–Crafts cyclization step, which afforded up to 36% yield. Attempts to perform a Friedel–Crafts cyclization of an intermediate phthalimide protected amino alcohol 13 did not give the desired protected (S)-7-MeO-AT. On the other hand, two new isoindolo[1,2-a]isoquinolinone derivatives 14 and 15, were isolated in 21 and 11% yield, respectively. The yield of 15 was improved to 70%.     

Asymmetric Synthesis of （R）- and （S）-Moprolol

A simple and effective procedure for the enantioselective synthesis of （R）- and （S）-moprolol was described. The key step was the asymmetric synthesis of enantiopure （R）- and （S）-guaifenesin, which were synthesized from enantioenriched （R）-3-chloro-l,2-propanediol and （S）-epichlorohydrin via kinetics of hydrolysis resolution of racemic epichlorohydrin by chiral Salen-Co^Ⅲ complex. The e.e. values of both the optical compounds were above 98%, and the chemical structures of the target compounds were confirmed by ^1H NMR, ^13C NMR, IR, and MS.     

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).     

Two additional 1,9-diarylnonanoid 3-glucosides from Erica cinerea among which an unusual α-dione in conformational equilibrium

Continuation of the phytochemical analysis of Erica cinerea fresh aerial parts resulted in the isolation of two new compounds with a very close chromatographic behavior. On the basis of spectroscopic evidence (UV, MS and NMR), the structures were established as (−)-(3S,6E)-1,9-bis(p-hydroxyphenyl)-3-hydroxynon-6-en-5-one 3-O-β-d-glucoside named 6,7-anhydroericaone 3-O-β-d-glucoside and (−)-(3S)-1,9-bis(p-hydroxyphenyl)-3-hydroxynonan-5,6-dione 3-O-β-d-glucoside named α-ericadione 3-O-β-d-glucoside. Unanticipated by its α-alkadione type structure —a very unusual feature in the plant kingdom— the latter metabolite was found as a mixture of the minor s-cis and the major s-trans conformers. Moreover, the GC-MS analysis of the aglycone moieties of such glucosides, pointed out the permanent absence of the molecular ion and the constant hydroxybenzylium base peak, as well as the conversion of the α-dione into the major α-keto-enol tautomer.     

Stereocontrolled synthesis of piperidine alkaloids, (−)-241D and (−)-isosolenopsin

Highly diastereocontrolled synthesis of alkaloids, (−)-241D and (−)-isosolenopsin was achieved in 7.7% and 5.3% yields, respectively, using a Barbier-type allylation of a chiral imine and d-proline catalyzed aldol addition reaction of a β-amino aldehyde with acetone as the key steps. The synthesis involves a nine-step sequence using (S)-valinate imine in a Barbier-type allylation for the first time.     

Chemistry of xanthorrhizol: synthesis of several bisabolane sesquiterpenoids from xanthorrhizol

(−)-Xanthorrhizol (1) isolated from the rhizomes of Curcuma xanthorrhiza has been transformed to several bisabolane-type sesquiterpenoids, in a stereoselective manner. 10R- and 10S-10,11-dihydro-10,11-dihydroxyxanthorrhizols (2, 3), (−)-curcuquinone (4), (−)-curcuhydroquinone (5), helibisabonol A (7) and allylic alcohol 8 have been prepared from xanthorrhizol in optically active forms. All the routes involved a Sharpless AD to introduce the stereogenic centre at C-10.     

Synthesis and characterization of polybinaphthalene incorporating chiral (R) or (S)-1,1′-binaphthalene and oxadiazole units by Heck reaction

Chiral conjugated polymers P-1 and P-2 were synthesized by the polymerization of (R)-3,3′-diiodo-2,2′-bisbutoxy-1,1′-binaphthalene ((R)-M-1) and (S)-3,3′-diiodo-2,2′-bisbutoxy-1,1′-binaphthalene ((S)-M-1) with 2,5-bis(4-vinylphenyl)-1,3,4-oxadiazole (M-2) under Pd-catalyzed Heck coupling reaction, respectively. Both monomers and polymers were analysed by NMR, MS, FT-IR, UV, DSC-TG, fluorescent spectroscopy, GPC and CD spectra. The chiral conjugated polymers exhibit strong Cotton effect in their circular dichroism (CD) spectra indicating a high rigidity of polymer backbone. CD spectra of polymers P-1 and P-2 are almost identical and have opposite signs for their position. These polymers have strong blue fluorescence.     

Synthesis of all the stereoisomers of 6-methyl-2-octadecanone, 6,14-dimethyl-2-octadecanone, and 14-methyl-2-octadecanone, the components of the female-produced sex pheromone of a moth, Lyclene dharma dharma

All of the stereoisomers of the components of the female-produced sex pheromone of a moth, Lyclene dharma dharma, were synthesized. They are (R)- and (S)-6-methyl-2-octadecanone, (6R,14R)-, (6R,14S)-, (6S,14R)-, and (6S,14S)-6,14-dimethyl-2-octadecanone, and (R)- and (S)-14-methyl-2-octadecanone. Enantiomers of citronellal and methyl (S)-3-hydroxy-2-methylpropanoate were the starting materials, and olefin cross metathesis was employed as the key reaction.     

Isolation, structural elucidation and synthesis of a novel antioxidative pseudo-di-peptide, Hanasanagin, and its biogenetic precursor from the Isaria japonica mushroom

The entomogenous ‘Hanasanagitake’ mushroom, Isaria japonica, is used as a folk medicine and as a traditional health food choice in Japan. A search for naturally occurring antioxidative compounds from the mushroom led to the isolation of a novel pseudo-di-peptide, named Hanasanagin, and a possible biogenetic precursor. The structures of the pseudo-di-peptides were determined as (R)-3,4-diguanidinobutanoyl-(S)-DOPA and (R)-3,4-diguanidinobutanoyl-(S)-tyrosine by spectral analysis, chemical synthesis and enzymatic conversion.     

Stereoselective total synthesis of (+)-varitriol

Stereoselective total synthesis of (+)-varitriol, an antitumor natural product, was accomplished by two versatile strategies starting from the commercially available d-(−)-ribose and ethyl (S)-lactate. The key steps involved in the synthesis of the target molecule are epoxidation, cyclization, dihydroxylation and Diels-Alder reaction.     

Synthesis of derivatives of (S)-2-alkanols, components of pheromones ofDrosophila mulleri andRhyzopertha dominica, from (S)-(+)-3,7-dimethylocta-1,6-diene

Effective routes for the synthesis of (S)-2-acetoxytridecane, the sex pheromone of the fruit flyDrosophila mulleri, and (S)-1-methylbutyl 2-methyl- and 2,4-dimethylpent-2E-enoates, components of the aggregation pheromone of the lesser grain borerRhyzopertha dominica, were developed on the basis of (S)-4-methylhex-5-en-1-yl tosylate accessible from (S)-(+)-dihydromyreene. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1929–1931, November, 2000.