Synthesis of Elemane Bis-Lactones from Santonin – Synthesis of the Reported Structure ofseco-Isoerivanin Pseudo Acid and Formal Synthesis of (+)-8-Deoxyvernolepin

The synthesis of the reported structure for seco-isoerivanin pseudo acid (1) and of an elemane bis-lactone 5 from santonin (4) through a common vinylic precursor 12 is described. Compound 5 is a known intermediate in a previous synthesis of the antitumor compound (+)-8-deoxyvernolepin (3). The vinyl group of 12 underwent a regio- and diastereoselective anti addition of an external electrophile and an intramolecular condensation to yield either the selenolactone 13 or the hydroxylactone 17. The lactones 13 and 17 served as key intermediates in the total synthesis of 1 and 5 respectively. A revision of the structure of seco-isoerivanin pseudo acid to the C-10 epimer is suggested on the basis …

Synthesis of Spirovetivane Sesquiterpenes from Santonin. Synthesis of (+)-Anhydro-?-rotunol and All Diastereomers of 6,11-Spirovetivadiene.

The synthesis of the spirovetivane sesquiterpenes (+)-anhydro-beta-rotunol and all the diastereomers of 6,11-spirovetivadiene in enantiomerically pure form has been achieved starting from santonin. The key step is the silicon-guided acid-promoted rearrangement of a 1-trimethylsilyl-4,5-epoxyeudesmane prepared from santonin in several steps involving lactone reductive opening, conjugate addition of TMSLi-CuCN, deoxygenation of a carbonyl group, and epoxidation. Rearrangement of the epoxide gave a spiro[4,5]decanediol which was used as a synthetic intermediate. From this compound, (+)-anhydro-beta-rotunol was prepared after elimination of the primary hydroxyl group in the side chain, followed…

Stereoselective Synthesis of (+)-11βH,13-Dihydroestafiatin, (+)-11βH,13-Dihydroludartin, (−)-Compressanolide, and (−)-11βH,13-Dihydromicheliolide from Santonin

Starting from 2 and 3, obtained from santonin (1), we have synthesized natural guaianolides 4-7. Chemoselective epoxidation of 2 gave (+)-11betaH,13-dihydroestafiatin (4), and epoxidation of 3 followed by regioselective elimination of the hydroxyl group afforded (+)-11betaH,13-dihydroludartin (5). Sharpless' mild regioselective ring-opening of 4 and 5 followed by hydrogenolysis yielded (-)-compressanolide (6) and (-)-11betaH,13-dihydromicheliolide (7), respectively.

Highly Diastereoselective Arylation of (S)-Mandelic Acid Enolate: Enantioselective Synthesis of Substituted (R)-3-Hydroxy-3-phenyloxindoles and (R)-Benzylic Acids and Synthesis of Nitrobenzophenones.

An easy access to substituted (R)-3-hydroxy-3-phenyloxindoles, (R)-benzylic acids, and benzophenones is described. The reaction of the lithium enolate of the (2S,5S)-cis-1,3-dioxolan-4-one derived from optically active (S)-mandelic acid and pivalaldehyde with several o- and p-halonitrobenzenes proceeds readily to give the corresponding arylation products in good yields and diastereoselectivities. The reduction of the nitro group with Zn/HCl/EtOH in the o-nitro arylation products with concomitant intramolecular aminolysis of the dioxolanone moiety leads directly to enantiomerically pure (R)-3-hydroxy-3-phenyloxindoles. On the other hand the basic hydrolysis of the dioxolanone moiety in all t…

NMR Spectroscopic Characterization and DFT Calculations of Zirconium(IV)-3,3′-Br2–BINOLate and Related Complexes Used in an Enantioselective Friedel–Crafts Alkylation of Indoles with α,β-Unsaturated Ketones

Experimental and theoretical studies on the structure of several complexes based on (R)-3,3'-Br-2-BINOL ligand and group (IV) metals used as catalysts in an enantioselective Friedel-Crafts alkylation of indoles with alpha,beta-unsaturated ketones have been carried out. NMR spectroscopic studies of these catalysts have been performed, which suggested that at room temperature the catalysts would form a monomeric structure in the case of Ti-IV and a dimeric structure in the cases of Zr-IV and Hf-IV. Density functional theory (DFT) calculations clearly corroborate the conclusions of these experimental spectroscopic studies. The dimeric structure with a doubly bridged motif [Zr-2(IV)(mu-(R)-3,3'…

Asymmetric diastereodivergent Michael addition of 2-chloromalonate esters to conjugated imines enabled by catalyst metal change

Despite recent progress in asymmetric diastereodivergent reactions leading to products bearing two stereogenic centers, little research has been devoted to processes were a stereogenic center and a double bond are formed. Here, we report the asymmetric diastereodivergent Michael addition of 2-chloromalonate esters to N-tosyl β,γ-unsaturated α-ketimino esters to give chiral α,β-dehydro-α-aminoesters bearing either a Z or E enamine moiety, using pyBOX-metal complexes. Diastereodivergency is achieved by simply changing the metal ion from a trivalent La(III) to a divalent Ca(II) ion, providing the Z or E enamines. Computational studies reveal the crucial role of London interactions between the …

ChemInform Abstract: Enantioselective Zinc-Mediated Conjugate Addition of Terminal Alkynes to Enones.

Zinc for conjugate alkynylation: The enantioselective conjugate addition of terminal alkynes to 2-arylidene-1,3-diketones in the presence of diethylzinc and a catalytic amount of (R)-VANOL has been developed. The reaction can be applied to different aromatic and heteroaromatic alkynes and enones, giving the expected products in good yield and with enantiomeric excesses up to 91%. The products can be enantiomerically enriched up to 99% ee by crystallization (see scheme).

ChemInform Abstract: A Non-Catalyzed Ring-Opening Aminolysis Reaction of Sesquiterpene Lactones.

Abstract Santonin (1) and other sesquiterpene lactones (6–10) react cleanly with pyrrolidine at room temperature to afford γ-hydroxyalkylamides, which by elimination with mesyl chloride in pyridine-benzene at 80°C give unsaturated alkylamides.

ChemInform Abstract: Synthetic Studies Toward Natural Furanosesquiterpenoids from Santonin. Synthesis of (+)-1,2-Dihydrotubipofuran.

Abstract Santonin (1) was converted into (+)-1,2-dihydrotubipofuran (13) via a synthetic pathway involving a very easy preparation of 7,11-ene-8,12-olide and 8,12-furan moieties and A-ring elaboration on the eudesmane framework.

ChemInform Abstract: The Reduction of α,β-Unsaturated Nitriles and α- Halonitriles with Sodium Hydrogen Telluride.

Abstract Sodium hydrogen telluride reacts chemoselectively with α,β-unsaturated nitriles and α-halonitriles linked to aromatic and aliphatic substituents to give the corresponding saturated nitriles with good yields.

Silicon-guided rearrangement of 10-methyl-4,5-epoxydecalins. Methyl versus methylene migration

The Lewis acid-promoted rearrangement of two 10-methyl-4,5-epoxydecalins bearing a trimethylsilyl (TMS) group on C-1 or C-9 has been studied. Migration of the C-9 methylene group to C-5 is the major reaction pathway when the TMS and the oxirane groups are on the same ring while methyl migration results exclusively when they are on different rings.

ChemInform Abstract: Stereoselective Synthesis of 7,11-Guaien-8,12-olides from Santonin. Synthesis of Podoandin and (+)-Zedolactone A.

Photochemical rearrangement of hydroxy ester 2, easily obtained from santonin (1), afforded butenolide 4, a good starting material for the synthesis of 7,11-guaien-8,12-olides. Compound 4 has been transformed into compound 10, which has been used for the synthesis of podoandin (5) and (+)-zedolactone A (ent-6). Regioselective elimination of the acetyl group on C10 afforded directly podoandin (5). For the synthesis of ent-6, a hydroxyl group has been regio- and stereoselectively introduced at the 4α-position through the 3α,4α-epoxide 15. The basic hydrolysis of the 10-acetyl group in compound 18 took place with concomitant intramolecular conjugated addition of the alkoxide to the butenolide …

Sesquiterpenes, flavonoids and lignans from Onopordon acaulon

Abstract From the methanol extract of Onopordon acaulon , four flavonoids, four lignans and three sesquiterpenes were isolated. Two eudesmane derivatives are described for the first time.

Catalytic enantioselective addition of terminal alkynes to aromatic aldehydes using zinc-hydroxyamide complexes

[EN] A mandelamide ligand, derived from (S)-mandelic acid and (S)-phenylethanamine, catalyzes the addition of aryl-, alkyl-and silyl-alkynylzinc reagents to aromatic and heteroaromatic aldehydes with good yields and good to high enantioselectivities.

Ultrasound assisted reductive cleavage of eudesmane and guaiane γ-enonelactones. Synthesis of 1α,7α,10αH-guaian-4,11-dien-3-one and hydrocolorenone from santonin

Abstract Ultrasound enhances the rate of reductive cleavage of the C6–oxygen bond of sesquiterpene enonelactones. trans-Eudesmanolides 1c–1g, cis-eudesmanolides 2a–2c, and trans-guaianolides 4a–4d react with Zn in acetic acid–H2O under sonochemical conditions to afford the corresponding sesquiterpene acids 3a–3g and 5a–5d, respectively in good yields. Starting from 5d two natural guaianes 1α,7α,10αH-guaian-4,11-dien-3-one (6) and hydrocolorenone (7) have been prepared in good yields through a straightforward sequence.

Enantioselective zinc-mediated conjugate addition of terminal alkynes to enones.

Zinc for conjugate alkynylation: The enantioselective conjugate addition of terminal alkynes to 2-arylidene-1,3-diketones in the presence of diethylzinc and a catalytic amount of (R)-VANOL has been developed. The reaction can be applied to different aromatic and heteroaromatic alkynes and enones, giving the expected products in good yield and with enantiomeric excesses up to 91%. The products can be enantiomerically enriched up to 99% ee by crystallization (see scheme).

Functionality transfer from C8 to C9 in sesquiterpenes. Synthesis of the named Herbolide E from artemisin.

Abstract The key intermediate 6 was obtained in five steps from artemisin (1). The spectroscopic characteristics of the synthetic product 7a reveal that the proposed structure for the natural herbolide E must be revised.

Synthesis of Spirovetivane Sesquiterpenes from Santonin. Synthesis of (+)-Anhydro-β-rotunol and All Diastereomers of 6,11-Spirovetivadiene

The synthesis of the spirovetivane sesquiterpenes (+)-anhydro-beta-rotunol and all the diastereomers of 6,11-spirovetivadiene in enantiomerically pure form has been achieved starting from santonin. The key step is the silicon-guided acid-promoted rearrangement of a 1-trimethylsilyl-4,5-epoxyeudesmane prepared from santonin in several steps involving lactone reductive opening, conjugate addition of TMSLi-CuCN, deoxygenation of a carbonyl group, and epoxidation. Rearrangement of the epoxide gave a spiro[4,5]decanediol which was used as a synthetic intermediate. From this compound, (+)-anhydro-beta-rotunol was prepared after elimination of the primary hydroxyl group in the side chain, followed…

ChemInform Abstract: Synthesis of Elemane Bis-lactones Structurally Related to Vernolepin.

Abstract The chemical transformation of santonin into an elemane bis -lactone structurally related to the antitumour compound vernolepin is reported. The transformation of ring A of santonin into a hemiacetal δ-lactone was achieved in eleven steps. The spectroscopic characteristics of the synthetic product obtained in this way revealed that the proposed structure for the natural product should be revised.

Antimicrobial Activity, in silico Molecular Docking, ADMET and DFT Analysis of Secondary Metabolites from Roots of Three Ethiopian Medicinal Plants

Mathewos Anza,1 Milkyas Endale,1 Luz Cardona,2 Diego Cortes,3 Rajalakshmanan Eswaramoorthy,1 Jesus Zueco,4 Hortensia Rico,4 Maria Trelis,5 Belen Abarca2 1Department of Applied Chemistry, School of Applied Natural Science, Adama Science and Technology University, Adama, Ethiopia; 2Department of Organic Chemistry, Faculty of Chemistry, University of Valencia, Burjassot, Spain; 3Department of Pharmacology, Faculty of Pharmacy, University of Valencia, Burjassot, Spain; 4Department of Microbiology and Ecology, Faculty of Pharmacy, University of Valencia, Burjassot, Spain; 5Parasites and Health Research Group, Department of Pharmacy, Pharmaceutical Technology and Parasitology, Faculty of Pharmacy…

Stereoselective Synthesis of 8,12-Furanoeudesmanes from Santonin. Absolute Stereochemistry of Natural Furanoeudesma-1,3-diene and Tubipofurane.

Ketobutenolide 3, easily obtained from santonin (1), has been transformed into two natural furanoeudesmanes 4 and 5, isolated from Commiphora molmol and Tubipora musica, respectively. trans- And cis-decalin systems were obtained by stereoselective reduction of the C(4)-C(5) double bond in 3 in the following way: hydrogenation of 3 over Pd/C followed by acidic treatment gave the cis isomer 10 as the major product; selective hydrogenation of the C(1)-C(2) double bond with the Wilkinson's catalyst followed by reduction with NaTeH yielded mainly the trans isomer 9. Compounds 9 and 10 were transformed into 4 and 5 in parallel sequences. Optical rotation and CD measurements of the synthetic produ…

ChemInform Abstract: Stereoselective Synthesis of 8,12-Furanoeudesmanes from Santonin. Absolute Stereochemistry of Natural Furanoeudesma-1,3-diene and Tubipofurane.

Ketobutenolide 3, easily obtained from santonin (1), has been transformed into two natural furanoeudesmanes 4 and 5, isolated from Commiphora molmol and Tubipora musica, respectively. trans- And cis-decalin systems were obtained by stereoselective reduction of the C4−C5 double bond in 3 in the following way:  hydrogenation of 3 over Pd/C followed by acidic treatment gave the cis isomer 10 as the major product; selective hydrogenation of the C1-C2 double bond with the Wilkinson’s catalyst followed by reduction with NaTeH yielded mainly the trans isomer 9. Compounds 9 and 10 were transformed into 4 and 5 in parallel sequences. Optical rotation and CD measurements of the synthetic products rev…

ChemInform Abstract: Synthesis of Elemane Bis-lactones from Santonin - Synthesis of the Reported Structure of seco-Isoerivanin Pseudo Acid and Formal Synthesis of (+)-8-Deoxyvernolepin.

The synthesis of the reported structure for seco-isoerivanin pseudo acid (1) and of an elemane bis-lactone 5 from santonin (4) through a common vinylic precursor 12 is described. Compound 5 is a known intermediate in a previous synthesis of the antitumor compound (+)-8-deoxyvernolepin (3). The vinyl group of 12 underwent a regio- and diastereoselective anti addition of an external electrophile and an intramolecular condensation to yield either the selenolactone 13 or the hydroxylactone 17. The lactones 13 and 17 served as key intermediates in the total synthesis of 1 and 5 respectively. A revision of the structure of seco-isoerivanin pseudo acid to the C-10 epimer is suggested on the basis …

ChemInform Abstract: Ring-Opening Aminolysis of Sesquiterpene Lactones: An Easy Entry to Bioactive Sesquiterpene Derivatives. Synthesis of (+)-β-Cyperone and (-)-Eudesma-3,5-diene from Santonin.

Abstract Santonin ( 1 ) and other sesquiterpene lactones ( 2–3 ) react with pyrrolidine and other cyclic secondary amines to afford γ-hydroxyamides, which by elimination with mesyl chloride in pyridine-benzene at 80°C give unsaturated amides 4a-4c, 5a-5c and 6 . Starting from amides 5a-5c a series of bioactive compounds against Locusta migratoria have been prepared, differing in the oxidation states of the C-3 and C-12 carbon atoms. Starting from amides 5a and 6 two conjugated diene eudesmanes (+)-β-cyperone ( 15 ) and (−)eudesma-3,5-diene ( 19 ) have been prepared involving an elaboration of the amide group of the side chain of the eudesmane skeleton.

ChemInform Abstract: Synthesis of (+)-Isoalantolactone and (+)-Isoalloalantolactone from (-) -Santonin.

Abstract This paper reports on the chemical conversion of (−)-santonin into (+)-isoalantolactone and (+)-isoalloalantolactone involving functionality transfer from C 6 to C 8 , refunctionalization of the ring A and the formation of the α-methylene-8 β,12-olide moiety.

Stereoselective synthesis of 7,11-guaien-8,12-olides from santonin. Synthesis of podoandin and (+)-zedolactone A.

Photochemical rearrangement of hydroxy ester 2, easily obtained from santonin (1), afforded butenolide 4, a good starting material for the synthesis of 7,11-guaien-8,12-olides. Compound 4 has been transformed into compound 10, which has been used for the synthesis of podoandin (5) and (+)-zedolactone A (ent-6). Regioselective elimination of the acetyl group on C10 afforded directly podoandin (5). For the synthesis of ent-6, a hydroxyl group has been regio- and stereoselectively introduced at the 4alpha-position through the 3alpha,4alpha-epoxide 15. The basic hydrolysis of the 10-acetyl group in compound 18 took place with concomitant intramolecular conjugated addition of the alkoxide to the…

ChemInform Abstract: Catalytic Enantioselective Addition of Terminal Alkynes to Aromatic Aldehydes Using Zinc-Hydroxyamide Complexes.

A mandelamide ligand, derived from (S)-mandelic acid and (S)-phenylethanamine, catalyzes the addition of aryl-, alkyl- and silyl-alkynylzinc reagents to aromatic and heteroaromatic aldehydes with good yields and good to high enantioselectivities.

ChemInform Abstract: Synthesis of Plagiochiline N from Santonin.

This article reports the transformation of O-acetylisophotosantonin, obtained by photochemical rearrangement of santonin, into plagiochiline N, an ent-2,3-secoaromadendrane isolated from Plagiochila ovalifolia. The synthesis was carried out in a sequence involving as the key steps (a) the substitution of the lactone moiety by a gem-dimethylcyclopropane ring through a synthetic intermediate having a C(6)-C(7) double bond and (b) the ozonolysis of the C(2)-C(3) bond followed by cyclization to the dihydropyran ring characteristic of plagiochiline N. Spectroscopic data of the synthetic product fully coincided with the reported data for the natural product.

ChemInform Abstract: Highly Enantioselective Zinc/Binol-Catalyzed Alkynylation of N-Sulfonyl Aldimines.

Synthesis of elemane bis-lactones structurally related to vernolepin

Abstract The chemical transformation of santonin into an elemane bis -lactone structurally related to the antitumour compound vernolepin is reported. The transformation of ring A of santonin into a hemiacetal δ-lactone was achieved in eleven steps. The spectroscopic characteristics of the synthetic product obtained in this way revealed that the proposed structure for the natural product should be revised.

Ultrasound assisted reductive cleavage of sesquiterpene γ-enonelactones

Abstract Ultrasound enhances the rate of reductive cleavage of the C 6 -oxygen bond of several cis - and trans - sesquiterpene γ-enonelactones. Interestingly ultrasound overrides the stereoelectronic requirements for the reductive cleavage of the most usually occurring sesquiterpene trans -lactones.

Synthesis of two natural 8-oxo-β-cyperone derivatives from (−)-santonin.

Abstract This paper reports on the chemical transformations of (−)-santonin into (+)-8-oxo-β-cyperone and (+)-12-hydroxy-8-oxo-β-cyperone involving 8-oxo group introduction and elaboration of the side chain.

Regio- and stereoselective oxyfunctionalization at C-1 and C-5 in sesquiterpene guaianolides

Abstract The regio- and stereoselective functionalization at C-1 and C-5 positions in a guaiane skeleton by allylic hydroxylation are described. The stereochemistry of the resulting compounds are identical to those of the majority of natural 1- and 5-hydroxy-guaianolides.

Catalytic Asymmetric Formal [3+2] Cycloaddition of 2-Isocyanatomalonate Esters and Unsaturated Imines: Synthesis of Highly Substituted Chiral γ-Lactams.

[EN] Unlike their isocyano and isothiocyanato analogues, isocyanato esters remain almost unexplored as formal 1,3-dipoles in asymmetric catalytic reactions. The first asymmetric formal [3+2] cycloaddition involving isocyanato esters and electrophilic alkenes is reported. Diisopropyl 2-isocyanatomalonate reacts with a,b-unsaturated N-(o-anisidyl) imines in the presence of a Mg(OTf)2¿BOX complex to give highly substituted chiral pyrrolidinones featuring a conjugate exocyclic double bond with excellent yields and enantiomeric excesses up to 99%. Several transformations of the resulting heterocycles, including the synthesis of a pyroglutamic acid derivative, have been carried out.

Lanthanum-pyBOX complexes as catalysts for the enantioselective conjugate addition of malonate esters to β,γ-unsaturated α-ketimino esters

[EN] In this paper, we report the application of chiral complexes of La(III) with pyBOX ligands as Lewis acid catalysts in the conjugate addition of malonic esters to N-tosyl imines derived from ß,gamma-unsaturated alfa-keto esters to give the corresponding chiral alfa,ß-dehydroamino esters. pyBOX complexes with La(III), Yb(III), Sc(III), and In(III) triflates were assessed in this reaction but only La(III) showed good activity and enantioselectivity, while Yb(III) provided the expected product with low yield and stereoselectivity, and the Sc(III) and In(III) complexes were completely inactive. The complex of La(OTf)3 with the diphenyl-pyBOX ligand prepared in situ provided the best results…

6-Prenyloxy-7-methoxycoumarin, a coumarin-hemiterpene ether from Carduus tenuiflorus

Abstract From the acetone extract of Carduus tenuiflorus , a new coumarin-hemiterpene ether was isolated, which was identified as 6-(3,3-dimethylallyloxy)-7-methoxycoumarin. The synthesis of this coumarin and that of its positional isomer 7-(3,3-dimethylallyloxy)-6-methoxycoumarin were carried out from esculetin. Two other coumarins, three lignans and three flavonoids were also isolated.

ChemInform Abstract: E,Z-Stereodivergent Synthesis of N-Tosyl α,β-Dehydroamino Esters via a Mukaiyama-Michael Addition

The stereodivergent synthesis of N-tosyl α,β-dehydroamino esters via a Mukaiyama–Michael addition is reported. The reaction of silylketene acetals with N-tosylimines derived from β,γ-unsaturated α-keto esters in dichloromethane provided the corresponding (Z)-α,β-dehydroamino esters while the (E)-isomers were obtained when the reaction was carried out in the presence of 10 mol% copper(II) triflate.

Highly enantioselective zinc/binol-catalyzed alkynylation of N-sulfonyl aldimines.

ChemInform Abstract: Asymmetric Conjugate Addition of Malonate Esters to α,β-Unsaturated N-Sulfonyl Imines: An Expeditious Route to Chiral δ-Aminoesters and Piperidones.

The asymmetric conjugate addition of malonate esters to α,β-unsaturated N-sulfonyl imines is catalyzed by PyBOX/La(OTf)3 complexes in the presence of 4 A MS. The reaction gives the corresponding E enamines bearing a stereogenic center at the allylic position with good yields and enantiomeric ratios up to 97:3. This reaction provides a synthetic entry to chiral δ-aminoesters and piperidones.

Synthesis of 3-Oxa-guaianolides from Santonin

Abstract This article reports on the transformation of santonin into two C10-epimeric 3-oxa-guaianolides which are 8-deoxyderivatives of several natural 3-oxaguaianolides isolated from Achillea species. The synthesis involved the photochemical rearrangement of the eudesmane skeleton into a guaiane skeleton and the transformation of the cyclopentane ring into a furan moiety with the concomitant loss of C3. Comparison of the NMR data of the synthetic products with those of the natural products confirms the β orientation of the hydroxyl group at C10 in the products isolated from Achillea.

Synthetic studies toward natural furanosesquiterpenoids from santonin. Synthesis of (+)-1,2-dihydrotubipofuran

Abstract Santonin (1) was converted into (+)-1,2-dihydrotubipofuran (13) via a synthetic pathway involving a very easy preparation of 7,11-ene-8,12-olide and 8,12-furan moieties and A-ring elaboration on the eudesmane framework.

ChemInform Abstract: The Synthesis of Bioactive Sesquiterpenes from Santonin

Abstract This article reviews the literature published in the last decade dealing with the transformation of α-santonin into bioactive or potentially bioactive sesquiterpenes. A number of syntheses starting from 8α-hydroxysantonin (artemisin) have also been included. Special emphasis has been placed on synthesized products that show biological activity. Major advances in this field include the application of new reagents and methodologies for the structural modification of the santonin skeleton and functionality, and its transformation into other sesquiterpenes, especially sesquiterpene lactones. The review has been organised into five parts: 1. Introduction: An overview of the structure an…

Asymmetric Conjugate Addition of Malonate Esters to α,β-UnsaturatedN-Sulfonyl Imines: An Expeditious Route to Chiral δ-Aminoesters and Piperidones

The asymmetric conjugate addition of malonate esters to α,β-unsaturated N-sulfonyl imines is catalyzed by PyBOX/La(OTf)3 complexes in the presence of 4 Å MS. The reaction gives the corresponding E enamines bearing a stereogenic center at the allylic position with good yields and enantiomeric ratios up to 97:3. This reaction provides a synthetic entry to chiral δ-aminoesters and piperidones.

Mg/BOX complexes as efficient catalysts for the enantioselective Michael addition of malonates to β-trifluoromethyl-α,β-unsaturated ketones and their N-tosyl imines

Abstract Magnesium (II)-BOX complexes catalyze the enantioselective Michael addition of malonates to β-trifluoromethyl enones and their N-sulfonyl imines to give ketones or (E)-enamines bearing a trifluoromethylated stereogenic center, respectively, with good yields and high enantiomeric excesses. Magnesium complexes proved to be more active and stereoselective than zinc and copper analogues in these reactions.

ChemInform Abstract: Ultrasound-Assisted Reductive Cleavage of Eudesmane and Guaiane γ-Enonelactones. Synthesis of 1α,7α,10αH-Guaian-4,11-dien-3-one and Hydrocolorenone from Santonin.

Abstract Ultrasound enhances the rate of reductive cleavage of the C6–oxygen bond of sesquiterpene enonelactones. trans-Eudesmanolides 1c–1g, cis-eudesmanolides 2a–2c, and trans-guaianolides 4a–4d react with Zn in acetic acid–H2O under sonochemical conditions to afford the corresponding sesquiterpene acids 3a–3g and 5a–5d, respectively in good yields. Starting from 5d two natural guaianes 1α,7α,10αH-guaian-4,11-dien-3-one (6) and hydrocolorenone (7) have been prepared in good yields through a straightforward sequence.

ChemInform Abstract: Synthesis of Two Natural 8-Oxo-β-cyperone Derivatives from (-)- Santonin.

Abstract This paper reports on the chemical transformations of (−)-santonin into (+)-8-oxo-β-cyperone and (+)-12-hydroxy-8-oxo-β-cyperone involving 8-oxo group introduction and elaboration of the side chain.

E,Z-Stereodivergent synthesis of N-tosyl α,β-dehydroamino esters via a Mukaiyama-Michael addition

The stereodivergent synthesis of N-tosyl α,β-dehydroamino esters via a Mukaiyama–Michael addition is reported. The reaction of silylketene acetals with N-tosylimines derived from β,γ-unsaturated α-keto esters in dichloromethane provided the corresponding (Z)-α,β-dehydroamino esters while the (E)-isomers were obtained when the reaction was carried out in the presence of 10 mol% copper(II) triflate.

Copper-catalysed enantioselective Michael addition of malonic esters to β-trifluoromethyl-α,β-unsaturated imines

[EN] Copper triflate-BOX complexes catalyse the enantioselective conjugate addition of methyl malonate to beta-trifluoromethyl-alpha,beta-unsaturated imines to give the corresponding enamines bearing a trifluoromethylated stereogenic centre with good yields, and diastereo- and enantioselectivities. The usefulness of the method has been shown with the synthesis of optically active beta-trifluoromethyl delta-amino esters and optically active trifluoromethyl piperidones.

New Sesquiterpene Lactones and Other Constituents fromCentaurea paui

Aerial parts of Centaurea paui afforded, in addition to several known sesquiterpene lactones, the two new elemanolides 2–4, the new elemane derivative 5 as well as the five new heliangolides 14–18. Their structures were elucidated by spectroscopic methods, especially high-field NMR spectroscopy. The structure of the heliangolide 12 previously isolated from this plant, has been confirmed by X-ray diffraction.

Sesquiterpene Lactones fromCentaurea paui

Abstract A new elemanolide and two new heliangolides as well as (2R,3R)-(+)-3-hydroxy-2-methyl-butyrolactone have been isolated from Centaurea paui. The structures were elucidated by high field NMR techniques and chemical transformation.

Rearrangement of 4,5-epoxy-9-trimethylsilyldecalines. Application to the synthesis of the natural eremophilane (-)-aristolochene.

Several 4,5-epoxy-9-trimethylsilyl-eudesmanes and 15-nor-eudesmanes, having different relative stereochemistry and substitution at the oxirane ring, have been prepared starting from (-)-carvone and subjected to acid-promoted rearrangement. The presence of the silicon at C9 favors two different main reaction pathways involving C14-methyl or C1-methylene migration through the stabilization of a C10 carbocation intermediate. Selective 1,2-migration of the bridgehead methyl group takes place with trisubstituted beta-epoxide and tetrasubstituted alpha-epoxide, yielding 4-hydroxy-eremophilane and 15-nor-eremophilane compounds, while the trisubstituted alpha-epoxide suffers successive rearrangemen…

Eudesmane and elemane derivatives from Onopordon acaulon

Abstract From the methanol extract of Onopordon acaulon 11 sesquiterpenes were isolated. Two elemane and three eudesmane derivatives are described for the first time.

Reductive cleavage of 2,2,2-trichloroethyl esters with sodium telluride

Abstract Carboxylic acids are regenerated from their 2,2,2-trichloroethyl esters by treatment with sodium telluride in dimethylformamide in smooth conditions and with good yields. The reaction conditions are compatible with other functional and protective groups such as methyl ester, acetate or tert-butyldimethylsilyl ethers.

Synthesis of (+)-Isoalantolactone and (+)-Isoalloalantolactone from (−)-Santonin

Abstract This paper reports on the chemical conversion of (−)-santonin into (+)-isoalantolactone and (+)-isoalloalantolactone involving functionality transfer from C 6 to C 8 , refunctionalization of the ring A and the formation of the α-methylene-8 β,12-olide moiety.

Synthesis of plagiochiline N from santonin.

This article reports the transformation of O-acetylisophotosantonin, obtained by photochemical rearrangement of santonin, into plagiochiline N, an ent-2,3-secoaromadendrane isolated from Plagiochila ovalifolia. The synthesis was carried out in a sequence involving as the key steps (a) the substitution of the lactone moiety by a gem-dimethylcyclopropane ring through a synthetic intermediate having a C(6)-C(7) double bond and (b) the ozonolysis of the C(2)-C(3) bond followed by cyclization to the dihydropyran ring characteristic of plagiochiline N. Spectroscopic data of the synthetic product fully coincided with the reported data for the natural product.

The Synthesis of Bioactive Sesquiterpenes from Santonin

Abstract This article reviews the literature published in the last decade dealing with the transformation of α-santonin into bioactive or potentially bioactive sesquiterpenes. A number of syntheses starting from 8α-hydroxysantonin (artemisin) have also been included. Special emphasis has been placed on synthesized products that show biological activity. Major advances in this field include the application of new reagents and methodologies for the structural modification of the santonin skeleton and functionality, and its transformation into other sesquiterpenes, especially sesquiterpene lactones. The review has been organised into five parts: 1. Introduction: An overview of the structure an…

Spiroterpenoids from Hypericum reflexum

Abstract Two new spiroterpenoids, hyperireflexolide A and B, were isolated from Hypericum reflexum . Their structures and stereochemistry were established by spectroscopic methods, including 13 C NMR, DEPT and HMQC, and X-ray data.

Oxidation of N-Acyl-pyrrolidones to Imides with CrO3·3,5-dimethylpyrazole

Abstract N -Acyl-pyrrolidones are easily obtained by treatment of N -acyl-pyrrolidines with CrO 3 ·3,5-dimethylpyrazole complex (CrO 3 ·3,5-DMP) at room temperature.

ChemInform Abstract: Ultrasound-Assisted Reductive Cleavage of Sesquiterpene γ- Enonelactones.

Abstract Ultrasound enhances the rate of reductive cleavage of the C 6 -oxygen bond of several cis - and trans - sesquiterpene γ-enonelactones. Interestingly ultrasound overrides the stereoelectronic requirements for the reductive cleavage of the most usually occurring sesquiterpene trans -lactones.

ChemInform Abstract: Reductive Cleavage of 2,2,2-Trichloroethyl Esters with Sodium Telluride.

Abstract Carboxylic acids are regenerated from their 2,2,2-trichloroethyl esters by treatment with sodium telluride in dimethylformamide in smooth conditions and with good yields. The reaction conditions are compatible with other functional and protective groups such as methyl ester, acetate or tert-butyldimethylsilyl ethers.

A non-catalyzed ring-opening aminolysis reaction of sesquiterpene lactones

Abstract Santonin (1) and other sesquiterpene lactones (6–10) react cleanly with pyrrolidine at room temperature to afford γ-hydroxyalkylamides, which by elimination with mesyl chloride in pyridine-benzene at 80°C give unsaturated alkylamides.

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