Optically active bisbibenzyls from Bazzania trilobata: isolation and stereochemical analysis by chromatographic, chiroptical, and computational methods

Bazzanin S, a new chlorinated bisbibenzyl of the isoplagiochin D type, as well as isoplagiochin D itself were isolated from the liverwort Bazzania trilobata. The structure of bazzanin S was elucidated based on extensive NMR spectral evidence and by mass spectrometry. Both macrocyclic compounds, bazzanin S and isoplagiochin D, as well as previously reported bazzanins exhibit optical activity, but are not enantiopure in nature. The enantiomeric ratios of a broad array of different cyclic bisbibenzyls, isoplagiochin D, bazzanins A-C and F-J, and bazzanin S, were determined by HPLC on a chiral phase. Exemplarily for the halogen-free parent compound isoplagiochin D, elucidation of the absolute configuration was achieved by quantum chemical CD calculations.     

The first total synthesis of acutifolone A, a pinguisane-type sesquiterpenoid isolated from the Japanese liverwort Porella acutifolia subsp. tosana

The first total synthesis of acutifolone A, a sesquiterpenoid carrying the bicyclo[4.3.0]nonane structure 1, was successfully achieved from the intermediate 6 produced by the intramolecular Diels-Alder reaction.     

Studies toward the total synthesis of nakiterpiosin: construction of the CDE ring system by a transannular Diels-Alder strategy

The transannular Diels-Alder (TADA) reaction was applied to the synthesis of the CDE ring system of nakiterpiosin (1). Tetracyclic compound 25 may be a key intermediate in the total synthesis of 1.     

Studies directed toward the synthesis of terreulactone A: rapid construction of the A, B, C rings

[structure: see text]. An efficient, rapid synthesis of the A, B, C rings of terreulactone A is described. Key steps in the synthesis include a diastereoselective benzylic acid rearrangement to create the desired quaternary center at C2 and a mild bromolactonization to assemble the lactonic ring A.     

Studies toward the synthesis of pinnatoxins: the B,C,D-dispiroketal fragment

A stereoselective synthesis of the tricyclic B,C,D-dispiroketal fragment of pinnatoxins is described. Both products of an efficient enzymatic resolution reaction are used to set the stereochemistry of C12 and C23, which have opposite configuration. The configuration of the ketal centers is established upon an optimized thermodynamically controlled spiroketalization.     

Studies toward a synthesis of C3-epimauritine D: construction of the macrocycle

We successfully synthesized a 14-membered cyclic enamide of C3-epimauritine D from the cis-2,3-pyrrolidinediol derivative. Treatment of the pyrrolidinediol with nitrobenzonitrile in an S_NAr reaction efficiently installed the desired aryl-alkyl ether linkage on the N-heterocyclic system. Macrocyclization was successfully achieved by the use of TFFH as the peptide coupling reagent in the presence of HOAt.     

Studies directed toward the synthesis of hamigeran B: a catalytic oxidative cyclization

An approach to the synthesis of hamigeran B is described. Key steps include a Tius-Nazarov cyclization and a palladium-catalyzed oxidative cyclization of an α-hydroxyenone.     

The total synthesis of sevanol,a novel lignan isolated from the thyme plant (Thymus armeniacus)

Recently, a novel lignan sevanol was isolated from the thyme plant Thymus armeniacus. During structure-functional elucidation it showed significant biological activity on ASIC3 acid sensing channels. Herein we describe the first synthesis of sevanol with a 3% overall yield. The construction of a dihydronaphthalene ring by oxidative dimerization of a protected dihydroxycinnamic acid ester in the presence of ferric chloride (III) is a key step in this first total synthesis of sevanol.     

Synthetic studies toward nortriterpenoids of schisandraceae family. Approach to the construction of functionalized C/D and A/B ring units of micrandilactone C and rubrifloradilactone B

Construction of 6/7 fused bicycles featuring C/D rings of micrandilactone C and rubrifloradilactone B is reported through IMDA reaction of properly designed substrates. Also a route to the construction of a tricycle having A/B ring of nortriterpenoids of schisandra family is reported using RCM and a bromonium ion initiated cycloetherification reaction as the key steps.     

A modified Prins reaction for the facile synthesis of structurally diverse substituted 5-(2-hydroxyethyl)-3,3-dihydrofurane-2(3H)-ones

Furanones are important synthetic intermediates commonly found in natural products, receptor ligands, and drug molecules. Unacceptable yields of substituted furanones obtained using a previously reported Prins reaction led to the development of a modified approach. Readily prepared substituted allylic esters were reacted under Prins reaction conditions catalyzed by a protic acid to provide structurally diverse substituted furanones in modest to good yields. The reaction goes through a protected caprolactone intermediate that was isolated and characterized for selected compounds. The approach supplies an efficient, versatile, and higher yield method for the synthesis of these important heterocyclic intermediates.     

A concise synthesis of d,l-brevianamide B via a biomimetically-inspired IMDA construction

A concise synthesis of brevianamide B has been accomplished using a biomimetically-inspired intramolecular Diels-Alder reaction to diastereoselectively form the characteristic bicyclo[2.2.2]diazooctane core.     

Studies toward the total synthesis of gambieric acids: convergent synthesis of the GHIJ-ring fragment having a side chain

A stereocontrolled synthesis of the GHIJ-ring fragment having a side chain of gambieric acids, which are potent antifungal polycyclic ether natural products, has been achieved. The synthesis features convergent assembly of the tetracyclic polyether skeleton by using aldol coupling and stereoselective construction of the J-ring side chain by a cerium chloride-promoted Julia-Kocienski reaction.     

Studies toward the total synthesis of angelmicin B (hibarimicin B): synthesis of a model CD-D' arylnaphthoquinone

[structure: see text] A synthesis of arylnaphthoquinone 22 corresponding to the CD-D' unit of angelmicin B via the Suzuki coupling of the D' arylboronic acid 15 with the CD bromonaphthoquinone 21 is described. The mild conditions for the Suzuki cross-coupling leading to 22 may prove to be useful for the eventual late-stage coupling of the two highly functionalized halves of angelmicin B.     

Diethoxyphosphinyl acetic acid hydrazide: a uniquely versatile reagent for the preparation of fused [5,5]-, [5,6]-, and [5,7]-3-[(E)-2-(arylvinyl)]-1,2,4-triazoles

Diethoxyphosphinyl acetic acid hydrazide is a unique reagent that provides a convenient and efficient process to prepare fused [5,5]-, [5,6]-, and [5,7]-3-[(E)-2-(arylvinyl)]-1,2,4-triazoles from aldehydes and alkoxyimines. The process involves three steps without isolation of any intermediates to afford 1,2,4-triazoles in modest to excellent overall yield.     

Studies toward the total synthesis of di- and sesterterpenes with a dicyclopenta[a,d]cyclooctane skeleton. Construction of a versatile A/B ring building block via a ring-closing metathesis reaction and carbocationic rearrangement

The cyclopentacyclooctane derivative 1, chosen as the key building block in a synthesis of terpenoid ophiobolates and fusicoccins, has been prepared from 2-methylcyclo-pent-2-en-1-one 5. Cyclization of the intermediate 1,9-diene of l,u configuration 10 under metathesis conditions (Grubbs’ catalyst 15) afforded the eight-membered ring product 13, whereas cyclization of the l,l diastereomer 9 produced a seven-membered ring analog 12. Cationic rearrangement of epoxide 26 occurred with methyl group migration to give ketone 27 as the major product.     

Studies directed toward the synthesis of rhizopodin: stereoselective synthesis of the C1-C15 fragment

A stereoselective synthesis of the C1-C15 fragment of a G-actin binding natural macrodiolide, rhizopodin was achieved using, as key steps, highly stereoselective acetate aldol reactions to build the C1-C7 fragment, one pot oxazole synthesis and an asymmetric Keck allylation reaction to build the C8-C15 fragment and finally, a Stille reaction to couple both the fragments.     

A new (R)-hydroxynitrile lyase from Prunus mume: asymmetric synthesis of cyanohydrins

A new hydroxynitrile lyase (HNL) was isolated from the seed of Japanese apricot (Prunus mume). The enzyme has similar properties with HNL isolated from other Prunus species and is FAD containing enzyme. It accepts a large number of unnatural substrates (benzaldehyde and its variant) for the addition of HCN to produce the corresponding cyanohydrins in excellent optical and chemical yields. A new HPLC based enantioselective assay technique was developed for the enzyme, which promotes the addition of KCN to benzaldehyde in a buffered solution (pH=4.5).     

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.     

Total synthesis of (R)-tylophorine by using an asymmetric hydrogenation of the allyl alcohol

An efficient synthesis of naturally occurring (R)-tylophorine is described. The alkaloid was prepared in seven steps from a known phenanthryl aldehyde with an overall yield of 14.2%. Asymmetric hydrogenation of an allyl alcohol was employed as a key step for installing a stereogenic center with good enantioselectivity (77% ee), and the ee value of the ω-chloro alcohol was improved to 95% by recrystallization. After azidation and oxidation of the enantio-enriched ω-chloro alcohol to the precursor of the Schmidt reaction, the chirality transfer in the stereospecific 1,2-migration furnished the chiral carbon in the alkaloid. Finally, a one-pot deformylation/Pictet-Spengler cyclization completed the total synthesis of (R)-tylophorine.     

An effective synthesis of N,N-dimethylamides from carboxylic acids and a new route from N,N-dimethylamides to 1,2-diaryl-1,2-diketones

Carboxylic acids were heated at 150 °C in DMF in the presence of 1.25 equiv of thionyl chloride to give corresponding N,N-dimethylamides in good yields. Tandem chlorination and amidation reactions occurred in the one-pot procedure. Dicarboxylic acids needed prolonged reaction time to produce bisamides in good yields. Some benzamides were efficiently converted into corresponding 1,2-diaryl-1,2-diketones (benzils) under acyloin condensation conditions in the presence of 4,4′-di-tert-butylbiphenyl (DBB) in THF. Ultrasonic irradiation effectively accelerates the reaction, but it is not critical. However, the presence of DBB is fatal to the reaction. Although a few synthetic methods for benzils from benzoic acids have been reported so far, this method is one of the most convenient and highly reproducible procedures.