ChemInform Abstract: Synthesis of Fluorinated and Non-Fluorinated Bicyclic Amidines Through Ring-Closing Metathesis.

Condensation of unsaturated esters (I) and (VII) with 1,2-diamines proceeds in the presence of trimethylaluminum providing imidazolines (III) and (VIII) which are further allylated giving suitable dienes (V) and (IX).

Enantioselective Synthesis of Cuparane Sesquiterpenes. Synthesis of (−)-Cuparene and (−)-δ-Cuparenol

(−)-Cuparene and (−)-δ-cuparenol, two cuparane-type sesquiterpenoids, were synthesized from β-cyclogeraniol in 47% and 27% overall yield, respectively, using a Katsuki−Sharpless asymmetric epoxidat...

ChemInform Abstract: Enantioselective Synthesis of Herbertane Sesquiterpenes: Synthesis of (-)-α-Formylherbertenol.

Abstract The synthesis of 4-hydroxy-3-[(1 S )-1,2,2-trimethylcyclopentyl]benzaldehyde [(−)-α-formylherbertenol 1 ], a herbertane-type sesquiterpene isolated from the leafy liverwort Herberta adunca , from β-cyclogeraniol is described. The synthesis is based on the previously described preparation of an enantiopure 1,2,2-trimethylcyclopentane synthon from which the characteristic aromatic moiety of 1 is elaborated, using a Robinson annulation and a palladium-catalysed methoxycarbonylation of an aryl triflate as key synthetic steps. The synthesis of the natural sesquiterpene (−)-α-herbertenol, also a natural sequiterpene, using the same methodology is also described.

Stereoselective synthesis of polyoxygenated atisane-type diterpenoids

Abstract A new stereoselective approach to polyoxygenated atisane-type diterpenes starting from (S)-(+)-carvone is described. The key steps involve an intramolecular Diels–Alder reaction, an unusual intramolecular diazo ketone cyclopropanation of an unsaturated ketone, and a regioselective endocyclic cleavage of a cyclopropyl carbinyl radical as key synthetic steps. The synthesis of the bioactive polyoxygenated atisanes atis-16(17)-en-3,14-dione ( 2 ) and 3R-hydroxy-atis-16(17)-en-2,14-dione ( 3 ) following this approach is presented.

The product of a regiospecific and stereoselective ene-reaction of a polycyclic terpenoid system

The X-ray structure of di­methyl (Z)-[(8aS,2R,4aR,4bR)-8a-methoxy­carbonyl-1,4a,7-tri­methyl-8-oxo-2,3,4,4a,4b,5,8,8a,9,10-deca­hydro­phenanthren-2-yl]-2-butenedioate, C25H32O7, confirmed its relative configuration. The structure shows the bend in the molecular skeleton as found for similar compounds. Weak intermolecular C—H⋯O interactions have been found in the crystal.

Synthesis of fluorinated allylic amines: Reaction of 2-(trimethylsilyl)ethyl sulfones and sulfoxides with fluorinated imines

A new synthesis of fluorinated allylamines through the reaction of 2-(trimethylsilyl)ethyl sulfones and sulfoxides (as vinyl anion equivalents) with imines and imino esters has been described. The process includes a TBAF-mediated fragmentation of 2-(trimethylsilyl)ethyl sulfones to afford the desired allylic amines. When the reaction is performed with the corresponding sulfoxides, the fragmentation takes place under the addition conditions, affording the final products in a single step. (C) 2007 Elsevier B.V. All rights reserved.

Synthesis and biological evaluation of cyclic derivatives of combretastatin A-4 containing group 14 elements

Several tricyclic compounds inspired by the structure of combretastatin A-4 and bearing group 14 elements have been synthesized by homocoupling lithiated aryl fragments followed by ring-closing metathesis. These tricyclic compounds and their diolefin precursors were evaluated for their antiproliferative action on the tumor cell lines HT-29, MCF-7, HeLa and A-549 and on the non-tumor cell line HEK-293. In addition, their effects on the cell cycle were also measured. The tricyclic compounds show antiproliferative activity similar to that of combretastatin A-4, even though they are not so active in arresting the cell cycle. However, some diolefin precursors are able to cause accumulation of ce…

Synthesis of oxygenated spongiane-type diterpenoids from carvone

Abstract A new diastereoselective approach to oxygenated spongiane diterpenes starting from ( R )-(−)-carvone is described. The carvone is incorporated as the B ring in the final spongiane framework using a B→AB→ABC→ABCD approach, which involves an intramolecular Diels–Alder reaction and the regioselective ring-opening of a dihydrofuran ring as key synthetic steps. The structure of the key intermediate in this approach has been verified by X-ray crystallography.

Synthetic studies on the preparation of oxygenated spongiane diterpenes from carvone

Abstract The paper describes a new diastereoselective approach to oxygenated spongiane diterpenes functionally related to natural dorisenones. The strategy followed for the preparation of the spongiane framework, a B→AB→ABC→ABCD approach, is based on the preparation of epoxydecalone 11 (AB rings) from R-(−)-carvone, followed by an intramolecular Diels–Alder reaction for the construction of the C ring (compound 26 ). Further manipulation of the Diels–Alder adduct functionality allows the completion of the spongiane framework and the elaboration of several oxygenated spongiane-type compounds. The structures of two compounds 27 and 31 , has been established by single-crystal X-ray crystallogra…

1H,13C and19F NMR spectroscopy of polyfluorinated ureas. Correlations involving NMR chemical shifts and electronic substituent effects

Seventeen N-(mono-, di-, tri-, tetra- and penta-fluorophenyl)-N′-(3-nitrophenyl)ureas were prepared and characterized. Complete assignment of their 1H, 13C and 19F NMR data was undertaken and the correlation of the chemical shifts of the ureido protons with field-inductive and mesomeric electronic substituent parameters was studied using the Swain–Lupton model. The best correlations were obtained when the study was limited to certain substitution patterns, e.g. non-ortho, mono-ortho- and di-ortho-fluorinated ureas, which reveal probable changes in conformations caused by the degree of ortho fluorination at the phenyl ring. Additionally, there is an excellent linear cross-correlation between…

Synthesis of fluorinated drimanes. Preparation of 9αF-drimenin

Abstract A stereoselective approach to the 9α-fluorinated analogue of the natural drimane sesquiterpene drimenin starting from β-ionone is described. β-Ionone is transformed into a bicyclic β-cetoester from which 9αF-drimenin is prepared through stereoselective electrophilic fluorination at the C-9 with N -fluorobenzenesulfonimide followed by Wittig methylenation, allylic bromination, bromine-hydroxyl exchange and γ-lactonization.

Preparation and Promotion of Fruit Growth in Kiwifruit of Fluorinated N-Phenyl-N‘-1,2,3-thiadiazol-5-yl Ureas

Seventeen phenyl-fluorinated analogues of thidiazuron [N-phenyl-N'-(1,2,3-thiadiazol-5-yl)urea, TDZ] have been prepared and characterized. The effects of each fluorinated urea on growth and quality of kiwifruits (Actinidia deliciosa) were evaluated by comparison with untreated (control) and TDZ-treated fruits. The results obtained showed a clear dependence of the growth-promoting activity of these fluorinated ureas on the pattern and degree of fluorine substitution in the phenyl ring. The most effective for promoting fruit growth was N-(2,3,5,6-tetrafluorophenyl)-N'-(1',2',3'-thiadiazol-5'-yl)urea at 25 ppm (at harvest, treated fruits were 58% heavier than untreated ones) followed by N-(3,5…

Preparation of 9a-Fluorinated Sesquiterpenic Drimanes and Evaluation of Their Antifeedant Activities

19 pages, figures, and tables statistics.

An Efficient Stereoselective Synthesis of Stypodiol and Epistypodiol

An efficient synthesis of stypodiol (1) and its epimer at C-14, epistypodiol (2), was accomplished starting from (S)-(+)-carvone (7). The synthesis of both epimeric compounds proceeds through common intermediates using an IMDA reaction, a sonochemical Barbier reaction, and an acid-catalyzed quinol−tertiary alcohol cyclization as key synthetic steps.

Improved Regioselectivity in Pyrazole Formation through the Use of Fluorinated Alcohols as Solvents: Synthesis and Biological Activity of Fluorinated Tebufenpyrad Analogs

The preparation of N-methylpyrazoles is usually accomplished through reaction of a suitable 1,3-diketone with methylhydrazine in ethanol as the solvent. This strategy, however, leads to the formation of regioisomeric mixtures of N-methylpyrazoles, which sometimes are difficult to separate. We have determined that the use of fluorinated alcohols such as 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as solvents dramatically increases the regioselectivity in the pyrazole formation, and we have used this modification in a straightforward synthesis of fluorinated analogs of Tebufenpyrad with acaricide activity. Fil: Fustero, Santos. Universidad de Valencia; España Fil…

Regiospecific and stereoselective ene reaction of the A-ring methylcyclohexene moiety of polycyclic terpenoid systems with dimethyl acetylenedicarboxylate

Polycyclic terpenoid compounds with a methylcyclohexene moiety at the A-ring, such as 1 and 7, give a regio- and stereoselective ene reaction when heated at low temperatures with dimethyl acetylenedicarboxylate. The structure and stereochemistry of the compound formed in the case of 1, e.g. 5, is determined by X-ray analysis.

Design, Synthesis, and Biological Evaluation of Novel Fluorinated Ethanolamines

The preparation of novel fluorinated allylamines and their use as key fragments for the stereoselective synthesis of hydroxyethyl secondary amine (HEA)-type peptidomimetics is described. Our strategy employs chiral sulfinyl imines as synthesis intermediates, by treatment of hemiaminal precursors with two equivalents of vinylmagnesium bromide. The subsequent oxidation of the allylic amines to the corresponding epoxides was achieved by treatment with methyl(trifluoromethyl)dioxirane. Finally, epoxide ring opening with a range of nitrogen nucleophiles provided a library of HEA-derived peptidomimetics with a phenyldifluoromethylene moiety. The biological evaluation of these derivatives revealed…

ChemInform Abstract: Stereoselective Construction of the Tetracyclic Scalarane Skeleton from Carvone.

The tetracyclic scalarane skeleton 22 has been constructed from (S)-(+)-carvone using two intramolecular Diels–Alder reactions as key synthetic steps.

ChemInform Abstract: Regiospecific and Stereoselective Ene Reaction of the A-Ring Methylcyclohexene Moiety of Polycyclic Terpenoid Systems with Dimethyl Acetylenedicarboxylate.

Diastereoselective synthesis of antiquorin and related polyoxygenated atisene-type diterpenes

Abstract A diastereoselective approach to polyoxygenated atisene-type diterpenes starting from (S)-(+)-carvone is described. The key steps used in the preparation of the atisene framework are an intramolecular Diels–Alder reaction, an intramolecular diazoketone cyclopropanation, an endocyclic cyclopropane ring cleavage and the regioselective reduction of an allylic bromide by a low-valent chromium species. The synthesis of natural atisanes antiquorin (1), atis-16-ene-3,14-dione (3), atis-16-ene-2,3,14-trione (8) and 3β-hydroxy-atis-16-ene-2,14-dione (9) following this approach is presented. Also described is the synthesis of 18-hydroxy-atis-16-ene-3,14-dione (5), the structure erroneously a…

ChemInform Abstract: Synthesis of Fluorinated Allylic Amines: Reaction of 2-(Trimethylsilyl)ethyl Sulfones and Sulfoxides with Fluorinated Imines.

A new synthesis of fluorinated allylamines through the reaction of 2-(trimethylsilyl)ethyl sulfones and sulfoxides (as vinyl anion equivalents) with imines and imino esters has been described. The process includes a TBAF-mediated fragmentation of 2-(trimethylsilyl)ethyl sulfones to afford the desired allylic amines. When the reaction is performed with the corresponding sulfoxides, the fragmentation takes place under the addition conditions, affording the final products in a single step.

6-Amino-7-Azaindoles synthesis from 2,6-diamino pyridine and diols

Abstract 6-Amino-7-azaindole has been prepared by combination of diaminopyridine and diols by means of an acceptorless dehydrogenative condensation. In addition, amino pyridines may also yield towards pyrrolo[3,2-b]pyrrole systems. All of these transformation have been performed with accessible heterogeneous catalysts: Pd/C and ZnO.

A unified synthetic approach to trachylobane-, beyerane-, atisane- and kaurane-type diterpenes

A general synthetic approach to the polycyclic carbon skeleton of biogenetically related trachylobane, beyerane, atisane, and kaurane diterpenes from carvone is described. The skeleton of these diterpenes is prepared from a common intermediate, that is, 25, readily prepared from carvone using an IMDA reaction and an intramolecular diazo ketone cyclopropanation of an unsaturated ketone as key steps. The tetracyclic diterpene ring systems are obtained from this key trachylobane-type intermediate through the regioselective reductive cleavage of the cyclopropane ring, after adequate modification of the functionalization around the tricyclo[3.2.1.02,7]octane moiety.

Syntheses of oxygenated spongiane diterpenes from carvone. Synthesis of dorisenone C

Abstract The synthesis of dorisenone C, a representative member of the spongiane-type diterpene family, is described. The synthesis follows a B→AB→ABC→ABCD approach and is based on the initial preparation of the previously known hydroxy-aldehyde 14 (AB rings) from R -(−)-carvone, followed by an intramolecular Diels–Alder reaction between an oxygenated diene moiety and an acetylenic dienophile for the construction of the C ring (compound 22 ), and adequate manipulation of the Diels–Alder adduct functionality for completion of the spongiane framework.

ChemInform Abstract: New Route to Herbertanes via a Suzuki Cross-Coupling Reaction: Synthesis of Herbertenediol.

Abstract The synthesis of herbertenediol, a relevant member of the herbertane-type sesquiterpene family, is described. The synthesis is based on a new general approach to this group of sesquiterpenes where the herbertane skeleton is constructed using a Suzuki cross-coupling reaction and a [2,3]-sigmatropic Still–Wittig rearrangement as key synthetic steps.

Synthesis of terpenoid unsaturated 1,4-dialdehydes. Pi-facial selectivity in the Diels-Alder reaction of the 1-vinyl-2-methylcyclohexene moiety of polycyclic systems with DMAD.

New route to herbertanes via a Suzuki cross-coupling reaction: synthesis of herbertenediol

Abstract The synthesis of herbertenediol, a relevant member of the herbertane-type sesquiterpene family, is described. The synthesis is based on a new general approach to this group of sesquiterpenes where the herbertane skeleton is constructed using a Suzuki cross-coupling reaction and a [2,3]-sigmatropic Still–Wittig rearrangement as key synthetic steps.

Synthesis of Fluorinated and Non-Fluorinated Bicyclic Amidines through Ring-Closing Metathesis

[EN] An efficient method for the synthesis of fluorinated and non-fluorinated imidazoazepines by a ring-closing metathesis reaction as the key step is described. The influence of the fluorine atoms on the preparation of these bicyclic systems is also studied.

Syntheses of Oxygenated Spongiane Diterpenes from Carvone. Synthesis of Dorisenone C.

Abstract The synthesis of dorisenone C, a representative member of the spongiane-type diterpene family, is described. The synthesis follows a B→AB→ABC→ABCD approach and is based on the initial preparation of the previously known hydroxy-aldehyde 14 (AB rings) from R -(−)-carvone, followed by an intramolecular Diels–Alder reaction between an oxygenated diene moiety and an acetylenic dienophile for the construction of the C ring (compound 22 ), and adequate manipulation of the Diels–Alder adduct functionality for completion of the spongiane framework.

Enantioselective synthesis of herbertane sesquiterpenes: synthesis of (−)-α-formylherbertenol

Abstract The synthesis of 4-hydroxy-3-[(1 S )-1,2,2-trimethylcyclopentyl]benzaldehyde [(−)-α-formylherbertenol 1 ], a herbertane-type sesquiterpene isolated from the leafy liverwort Herberta adunca , from β-cyclogeraniol is described. The synthesis is based on the previously described preparation of an enantiopure 1,2,2-trimethylcyclopentane synthon from which the characteristic aromatic moiety of 1 is elaborated, using a Robinson annulation and a palladium-catalysed methoxycarbonylation of an aryl triflate as key synthetic steps. The synthesis of the natural sesquiterpene (−)-α-herbertenol, also a natural sequiterpene, using the same methodology is also described.

Stereoselective construction of the tetracyclic scalarane skeleton from carvone

The tetracyclic scalarane skeleton 22 has been constructed from (S)-(+)-carvone using two intramolecular Diels–Alder reactions as key synthetic steps. Abad Somovilla, Antonio, Antonio.Abad@uv.es ; Agullo Blanes, M Consuelo, Consuelo.Agullo@uv.es ; Cuñat Romero, Ana Carmen, Ana.Cunat@uv.es ; Llosa Blasco, Maria Carmen, Carmen.Llosa@uv.es

CCDC 626412: Experimental Crystal Structure Determination

Related Article: Antonio Abad, Consuelo Agulló, Ana C. Cuñat, Ignacio de Alfonso Marzal, Antonio Gris, Ismael Navarro, Carmen Ramírez de Arellano|2007|Tetrahedron|63|1664|doi:10.1016/j.tet.2006.11.083