Highly efficient total synthesis of Δ-PGJ2, 15-deoxy-Δ-PGJ2, and their analogues

Palladium-catalyzed reaction of TBS ether of 4-cyclopentene-1,3-diol monoacetate (>95% ee) with an anion derived from methyl malonate and a base such as t-BuOK and LDA proceeded highly efficiently and reproducibly. The product obtained in >90% isolated yield was transformed in five steps into the key cyclopentenone possessing the α-chain at the γ position. Aldol reaction of this enone with the ω-chain aldehyde afforded the aldol adduct, and exposure of the derived mesylate to Al₂O₃ furnished the cross-conjugated dienone of the full structure. Finally, functional group manipulation furnished Δ¹²-PGJ₂ efficiently. Similarly, 15-deoxy-Δ^12,14-PGJ₂, 5,6-acetylene analogues, and a 5,6-dihydro analogue were synthesized.     

Total synthesis of Δ-PGJ2, 15-deoxy-Δ-PGJ2, and related compounds

A key cyclopentenone possessing the α-chain was synthesized from TBS ether of 4-cyclopentene-1,3-diol monoacetate, and submitted to aldol reaction at the α^′-position with the ω-chain aldehydes followed by dehydration to produce the title compounds. In a similar manner, 5-dehydro compounds (acetylene analogues) were synthesized successfully. In addition, palladium-catalyzed reaction of 4-cyclopentene-1,3-diol monoacetate with methyl malonate, the first step of the synthesis, was improved to afford the product in high yield by using t-BuOK or LDA in place of NaH.     

Short and stereoselective synthesis of polysubstituted cyclohexanones

Two equivalents of dimethyl 1,3-acetonedicarboxylate reacted with α,β-unsaturated aldehydes to form novel polysubstituted cyclohexanones 2 in an efficient one-step procedure. The reactions proceeded at room temperature in the presence of catalytic amount of sodium methoxide, affording the products in high yields in a remarkably stereoselective manner. The products are of possible biological interest.     

Enantiopure arenesulfenic acids as intermediates in stereoselective synthesis

New transient arenesulfenic acids were involved in the synthesis of enantiopure 2-arylsulfinyl-1,3-dienes, showing central or axial chirality of the substituted arene residue, apart from the chirality related to the stereogenic sulfur atom. Some of the obtained dienes, that is, (S_a,S_S)- and (S_aR_S)-2-(2′-hydroxy-1,1′-binaphthalen-2-sulfinyl)-3-methyl-1,3-butadienes, were subjected to diastereoselective Diels-Alder cycloadditions with N-methylmaleimide. Removal of the arylsulfoxide auxiliary, in the major adduct, was accomplished by reductive cleavage with Raney nickel.     

An efficient multicomponent stereoselective synthesis of 1,2,4-trisubstituted 1,3-thiazetidines

The first one-pot three-component coupling reaction of O,O-diethyl hydrogen phosphorodithioate, aldehydes, and aldimines affording 1,2,4-trisubstituted 1,3-thiazetidines is reported. The product is obtained in moderate to high yields (45-94%) and has excellent diastereoselectivity (90-96%) in favour of the cis isomer. Shorter reaction times, ambient temperature, operational simplicity, and high yields are the salient features of the present procedure.     

Structure elucidation and stereoselective total synthesis of pavettamine, the causal agent of gousiekte

The structure elucidation of a novel natural product pavettamine (1), the causal agent of the plant toxicosis gousiekte, is reported. The structure was defined by analysis of NMR and MS data and the relative configuration followed from the ¹³C NMR data of the acetonide derivative. The absolute stereochemistry was established by total synthesis from (2S)-malic acid using chiral sulfoxide methodology as (2S,4R,8R,10S)-1,11-diamino-6-aza-undecane-2,4,8,10-tetraol.     

Efficient synthesis of fluorobenzyloxoimidazolidinone derivatives: precursors for the radiosynthesis of [F]fluorophenylamino acids

This paper describes an efficient synthesis of fluorobenzyloxoimidazolidinone derivatives. The title compounds 1a, 1b and 1c could be prepared with high diasteromeric purity (>99%) and overall yields of 19%, 48% and 41% in a ten or six-step synthetic procedure, respectively. These compounds are used as precursors for isotopic ¹⁸F-labelling.     

Studies on synthesis of spirolactone annulated bicyclo[2.2.2]octanes: tricyclic core of yaoshanenolides

A stereoselective approach to tricyclic core of yaoshanenolides from simple aromatic precursor is described. Cycloaddition of highly reactive spiroepoxycyclohexa-2,4-dienone, stereoselective Grignard reaction, alkylation, and ring-closing metathesis reaction are the key features of our approach.     

A novel and highly stereoselective route for the synthesis of non-racemic 3-substituted isoindolin-1-one targets

A new, versatile and highly stereoselective approach for the synthesis of non-racemic 3-substituted isoindolin-1-ones is described from a readily available chiral template. The potential of this new protocol is demonstrated through the synthesis of an enantiomerically enriched 3-alkyl N-H isoindolin-1-one target with an e.e. of 98%.     

Antimony chloride doped on hydroxyapetite catalyzed stereoselective one-pot synthesis of pyrano[3,2-c]quinolines

Antimony chloride doped on hydroxyapetite (SbCl₃-HAP) has been shown to be an efficient catalyst for the one-pot stereoselective synthesis of trans-pyrano[3,2-c]quinolines from anilines, benzaldehydes and 3,4-dihydro-2H-pyran (DHP). The catalyst was recoverable and reusable.     

A concise methodology for the synthesis of (−)-Δ-tetrahydrocannabinol and (−)-Δ-tetrahydrocannabivarin metabolites and their regiospecifically deuterated analogs

The availability of tetrahydrocannabinols (Δ⁹-THC), tetrahydrocannabivarins (Δ⁹-THCV), and their metabolites in both their undeuterated and deuterated forms is critical for the analysis of biological and toxicological samples. We report here a concise methodology for the syntheses of (−)-Δ⁹-THC and (−)-Δ⁹-THCV metabolites in significantly improved overall yields using commercially available starting materials. Our approach allowed us to obtain the key intermediates (6aR,10aR)-9-nor-9-oxo-hexahydrocannabinols in four steps from (+)-(1R)-nopinone. This was followed by an optimized Shapiro reaction to give the (−)-11-nor-9-carboxy-metabolites, which were converted to their respective (−)-11-hydroxy analogs. The synthetic sequence involves a minimum number of steps, avoids undesirable oxidative conditions, and incorporates the costly deuterated resorcinols near the end of the synthetic sequence. This methodology enabled us to synthesize eight regiospecifically deuterated (−)-Δ⁹-THC and (−)-Δ⁹-THCV metabolites in a preparative scale and high optical purity without deuterium scrambling or loss.     

Complexes of aluminium(III) with picolinic and pipecolinic acids: An27Al-NMR investigation

Summary Aluminium-27 NMR has been employed for the study of the interaction of Al(III) with picolinic (pic-H) and pipecolinic (pip-H) acids in aqueous solution at variablepH. In the reaction with picolinic acid distinct peaks for hydrated Al(III), 1:1 and 1:2 Al-picolinate complexes, as well as a mixed hydroxo-picolinato complex Al(pic)₂OH are observed. An insoluble 1:3 picolinate complex is formed atpH 3. Pipecolinic acid forms 1:1 and 1:2 Al-pipecolinate complexes. No hydroxy-pipecolinate species are formed, however, and the 1:2 complex is deprotonated abovepH 4.5 to colin- (pic-H) und Pipecolinsäure (pip-H) in wäßriger Lösung bei verschiedenenpH angewandt. Bei Al(pip)(H_–1 pip) have been isolated and characterized by elemental analysis, IR and¹H-NMR.

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Komplexe von Aluminium(III) mit Picolin- und Pipecolinsäure: Eine²⁷Al-NMR-Untersuchung

Zusammenfassung ²⁷Al-NMR wurde zur Untersuchung von Wechselwirkungen von Al(III) mit Picolin-(pic-H) und Pipecolinsäure (pip-H) in wäßriger Lösung bei verschiedenenpH angewandt. Bei der Reaktion mit Picolinsäure wurden separate Signale für hydratisiertes Al(III), 1:1 und 1:2 Al-Picolinat-Komplexe und auch für gemischte Hydroxo-picolinat-Komplexe Al(pic)₂OH beobachtet. BeipH3 wird unlöslicher Picolinat-Komplex gebildet. Pipecolinsäure geht 1:1 und 1:2 Al-Pipecolinat-Komplexe ein. Es werden keine Hydroxo-Pipecolinat-Komplexe gebildet. Der 1:2 Komplex wird über einempH von 4.5 deprotoniert und ergibt den unlöslichen Komplex Al(pip)(H_–1 pip). Die [3, 4] as well as those undergoing dialysis treatment for chronic renal failure [5]. taranalyse, IR und¹H-NMR charakterisiert.

     

Diisophorone and related compounds. Part 1413C-nuclear magnetic resonance spectra of diisophorone carboxylic acids

The¹³C-nmr spectra of a group of diisophorone carboxylic acids have been determined and fully assigned. The spectral data confirm, in some cases decisively, the formulation of members of this series of compounds. In the light of the spectral information, the stereochemistry of the C(4)-C(5)-region of the diisophorone ring-system is discussed, with special reference to the configuration of the 4-substituents.

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Diisophorone und verwandte Verbindungen, 14. Mitt.:¹³C-NMR Spektren von Diisophoron-carbonsäuren

Zusammenfassung Die¹³C-Kernresonanzspektren einer Anzahl von Diisophoron-carbonsäuren wurden aufgenommen und die Signale den Atomen des Kohlenstoffgerüstes zugeordnet. Die so erhaltenen Beziehungen ermöglichen ihrerseits die Bestätigung — und in gewissen Fällen die entscheidende Sicherung — der Struktur weiterer Beispiele dieser Verbindungsreihe. Die sterische Anordnung des C(4)-C(5)-Bereiches im Diisophoron-Ring-System, insbesondere die Konfiguration von 4-Substituenten, wird an Hand der spektroskopischen Ergebnisse erörtert.

     

A cross-metathesis approach for the synthesis of tedanolide and 13-deoxytedanolide: stereoselective synthesis of the C3-C16 segment

A unified synthetic strategy has been devised for the synthesis of both tedanolide and 13-deoxytedanolide, which involves a cross-metathesis reaction as the key step. We report herein the stereoselective synthesis of the C3-C16 segment (+)-5b and subsequent manipulation of the C12-C13 double bond leading to the preparation of both tedanolides.     

Cofluorescence of Eu in complexes of aromatic carboxylic acids

The fluorescence of Eu³⁺ in certain Eu³⁺–aromatic acid complexes were enhanced by over two orders of magnitude, by the addition of La³⁺; a process referred to as cofluorescence. Cofluorescence was observed only with certain aromatic acid ligands; trismesic acid, pyromellitic acid and mellitic acid; thereby clearly establishing a correlation between the structure of the ligand and the process of cofluorescence. While cofluorescence has been extensively studied using β-diketones as ligands, our studies demonstrate cofluorescence for the first time in ligands other than β-diketones. Furthermore, the mechanism of cofluorescence in the aromatic acid complexes studied by us appears to be different from that operating in the β-diketones. While intermolecular energy transfer is believed to occur in the β-diketones, formation of polynuclear complexes appears to be responsible for cofluorescence in the aromatic acid ligands.     

Efficient synthesis of orthogonally protected anti-2,3-diamino acids

An asymmetric synthesis of anti-2,3-diamino acids is reported. The enolates of N,N-dibenzylated β³-amino esters were treated with di-tert-butyl azodicarboxylate (DBAD) to afford their N′,N″-di-Boc-2-hydrazino derivatives with excellent anti diastereoisomeric ratio. Final Boc removal and reductive cleavage of the hydrazino bond led to the expected 2,3-diamino esters having only one free amino group. In comparison with other asymmetric C-2 amination procedures, this method does not need the use of expensive chiral reagents and/or chiral auxiliaries, while leads to products which can be orthogonally protected.     

Highly diastereoselective preparation of anti-α,β-dialkyl β-amino acids containing natural α-amino acid side chains

An efficient synthesis of anti-2-alkyl β³-amino acids was developed starting from the fully protected β³-amino acids. The strategy allows the introduction of the side chain of natural α-amino acids such as Ala, Phe and Ser at the C-2 position, with high diastereoselectivity. The preparation of 2-methyliden-β³-amino acids is also reported. This methodology does not need the use of expensive chiral reagents and/or chiral auxiliaries, and leads to compounds with orthogonal protecting groups.     

Short and stereoselective synthesis of manzacidins A and C, and their enantiomers

A short and stereoselective synthesis of manzacidins A and C, and their enantiomers was achieved via stereoselective hydrogenation reactions of dehydroamino acid esters 5-8 using a chiral Rh catalyst.     

HClO4-SiO2 catalyzed stereoselective synthesis of β-amino ketones via a direct Mannich-type reaction

The HClO₄-SiO₂ catalyzed three-component, one-pot Mannich reaction of ketones, aromatic aldehydes and aromatic amines is carried out in ethanol to afford the corresponding β-amino ketones in good yields and high stereoselectivities in favor of the anti-isomer. Three new compounds are reported.     

Total synthesis of (±)-camphorataimides and (±)-himanimides by NaBH4/Ni(OAc)2 or Zn/AcOH stereoselective reduction

Maleic anhydride 1 of Antrodia camphorate, which can be isolated from Chinese herbal medicine, is achieved in which the longest linear sequence is only five steps, in 40% overall yield from commercially available succinic anhydride. The crucial antrodimides 3 and 2 can be readily transformed by the chemoselective reduction with Zn/AcOH and NaBH₄/Ni(OAc)₂·4H₂O to afford the naturally occurring camphorataimides, 4 and 5, in high yields as well, respectively. This synthetic strategy can also be modified to give access to a variety of different maleic acid derivatives, himanimides 6-8.