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Starting from ethyl (1 S,4 R)-4-hydroxy-2-methylcyclopent-2-ene-1-carboxylate,as a common enantiopure building block readily obtained by enzymatickinetic resolution of the corresponding racemic derivative, 3′-methylcarbovir,3′-methylabacavir, and three modified analogues were synthesizedvia the linear construction of the purine heterocycles. These derivativeswere evaluated as potential agents against HIV-1, HIV-2, and otherimportant viral pathogens. None of the new compounds had significantantiviral activity at a concentration of 100 μg˙mL -¹ ,which was the highest concentration tested.

A series of 3'-methyl-branched and purine-modified analogues of aristeromycin were synthesized via the SN 2 displacement of a key triflate, which was prepared from a readily available enantiopure building block in eight steps. The synthesized compounds were evaluated as potential antiviral agents against important viruses. Only the 2,6-diaminopurine derivative exhibited moderate activity against vesicular stomatitis virus.

Danishefsky's taxol CD ring key intermediate is synthesized in 15 steps and 11.4% overall yield from a readily available starting material. Absolute stereochemistry of the starting material and stereocontrolled steps determine the absolute configuration of the five requisite contiguous stereocenters.

The first enantioselective synthesis of two new monoterpene aldehyde-esters from Bupleurum gibraltaricum, starting from an enantiopure building block, is described. The key step is a strictly controlled esterification to afford the somewhat unstable target compounds. The previously unknown absolute stereochemistries of these natural products have been established.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Starting from a readily available enantiopure building block, a straightforward enantioselective approach to 3′-methyl-2′,3′-β-oxirane-fused carbanucleosides bearing adenosine analogues is detailed. The key steps in the syntheses involved a lipase-catalyzed regioselective monoacylation of a diol to obtain the key intermediate and direct coupling of this key intermediate with diversely substituted purine nucleobases under Mitsunobu reaction conditions providing only the N9 target molecules.

This paper describes the racemic and stereoselective synthesis of novel conformationally locked 3'-methyl-2',3'-oxiranefused carbocyclic nucleosides (nucleosides numbering). The key step is the direct coupling of an alcohol bearing the 1-methyl-6-oxabicyclo[3.1.0]hexane scaffold with diversely substituted purine nucleobases under Mitsunobu reaction conditions providing only the N 9 target molecules.

A convenient chemoenzymatic enantioconvergent access to enantiomerically pure (+)- or (-)-4-hydroxy-3-methyl-2-cyclohexenone is described using a one-pot two-step kinetic resolution-stereoinversion protocol followed by hydrolysis. The key step of the sequence is the spontaneous elimination of an undesired stereocenter. The choice between enzymatic acyl transfer or ester alcoholysis of the corresponding racemic starting material, together with the selectivity of a lipase, determines the absolute configuration of the desired single enantiomer.

This paper reports the straightforward enantioselective synthesis of (+)-ancistrofuran starting from a readily available enantiopure building block. A stereofacial directed diastereoselective addition of an organocerate for the installation of the required stereogenic center served as the key step. In addition, the efficient conversion of an intermediate hydroxy aldehyde to the one-carbon homologated cyanide was developed. The sequence was achieved by the mild formation of a cyanohydrin and the subsequent one-pot two-step Barton–McCombie double deoxygenation of the hydroxyl groups.

An enantioselective synthesis of (+)-1,14-herbertenediol, and a formal enantioselective synthesis of (−)-α-herbertenol and (−)-herbertenediol, employing a lipase-promoted and a key stereoselective alkylation of a cyclopentane unit based methodology, are described. Molecular mechanics considerations that could account for the major role played by the substitution pattern of the benzene nucleus in the herbertane framework in comparison with those of the cuparane framework are described. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

The first enantioselective synthesis of tochuinyl acetate and dihydrotochuinyl acetate, two natural marine products isolated from Tochuina tetraquetra and Gersemia rubiformis, has been achieved starting from an enantiopure building block. The key feature of the present synthesis is complete control of two vicinal quaternary stereogenic centers present in the natural products and elucidation of their absolute stereochemistry, which was previously unknown. Furthermore, starting from the enantiomer of the same building block, the applied methodology provided a new approach towards natural (R)-(+)-β-cuparenone.

The enzymatic kinetic resolution of a suitable hydroxylated precursor of the deoxygenated molecule 3, a key intermediate in a synthesis of the cuparane skeleton, was investigated by screening a range of lipases for enantioselective transesterification with vinyl acetate. CAL-B proved to be the best lipase, affording both enantiomers in high enantiomeric excess (>98% ee). Single-crystal X-ray diffraction analysis enabled assignment of the absolute configuration and the enantiospecificity of the tested lipases.

We herein report the first enantioselective synthesis of two new monocyclic sesquiterpenes from Artemisia chamaemelifolia starting from an enantiopure building block. The key feature of the present approach is to allow complete control of all the stereogenic centers present in the natural products and to elucidate their absolute stereochemistry, which to date is unknown.

) was deter-mined by the ratio of the peak areas obtained by GC sep-aration on a chiral phase (see Exp. Sect.). The enantiomersof the remaining alcohol and those of the produced acetatewere perfectly separated. After 16 h at room temp., the act-ive enzyme was recovered for reuse by filtration. Concentra-tion of the filtrate and column chromatography on silica gelafforded 58% of the unreactive alcohol (1

Based upon a remarkable β-face diastereoselection, a stereocontrolled construction of bicyclic systems with the appropriate stereochemical disposition of the substituents belonging either to a Baccatin-I C-ring precursor or a Taxol® CD-ring precursor is reported.

An efficient enantioselective synthesis of fully-oxygen, ated Taxol® A-ring subunit has been achieved using (-)-karahana lactone, (-)-2, as an enantiopure starting building-block and a diastereoselective allylic hydroxylation as the key step.

The first enantioselective total synthesis of both enantiomers of lancifolol has been accomplished using a Z -stereoselective Peterson olefination and a palladium-catalyzed cross-coupling reaction as key steps. This approach allows us to correlate the relationship between absolute configuration and specific rotation, to date both unknown.

The enantioselective synthesis and determination of the absolute configuration of the title compound (−)-1 has been carried out starting from karahana lactone (+)-2 as an enantiopure building block. The structure was confirmed by single crystal X-ray diffraction analysis and the optical purity of (−)-(1S,3R)-elegansidiol (−)-1 verified by chiral HPLC.

A straightforward enantioselective synthesis of both enantiomers of karahana lactone is described starting from enantiopure (R) or (S)-4-hydroxy-3-methyl-cyclohex-2-en-1-one. The key step of the sequence is an acid-induced domino reaction with three pathways running. Because of the first description of karahana lactone as a solid, the structure was secured by X-ray structural analysis.

Enzymatic-mediated kinetic acylation of allylic(hydroxymethyl)methylenecyclopentane building blocks (±)- 1a , b is reported using various commercially available lipases. Lipase Amano AK ( Pseudomonas sp.) proved to be the best lipase in the case of (−)- 1b which was obtained with a 96% enantiomeric excess. Single crystal X-ray diffraction analysis, using the (1 S ,4 R )-camphanate derivative of (−)- 1b , helped us to assign the S absolute configuration of (−)- 1b and the enantiomeric specificity of the tested lipases.

A short and efficient enantiospecific total synthesis of natural (+)-laurene and its enantiomer is described. The methodology was developed by employing a stereoselective H-ene reaction of an isocyclic allyltrimethylsilane with paraformaldehyde, followed by a lipase-mediated kinetic resolution of the racemic key intermediate.

Enantiopure ethyl (1 S,4 R)-4-hydroxy-2-methylcyclopent-2-ene-1-carboxylate, readily obtained by enzymatic kinetic resolution of the corresponding racemic derivative, provided a convenient starting building block for an 11-step chiral preparation of (-)-3′-methylaristeromycin with 23% overall yield.

The TiCl 4 -mediated reactivity of five complementary substituted methylenecyclopropyl ketones with allyltrimethylsilane has been studied. The regioselectivity of the reaction, which affords functionalized methylene and/or alkylidenecyclopentanes in good yields, depends on the substitution of the cyclopropanic carbon α to the carbonyl function. The reaction occurs via a stereoselective cleavage of the carbocycle followed by a tandem [3+2] cycloaddition of the resultant ( Z )-1,3-zwitterion with allyltrimethylsilane that acts as the 1,2-partner in a synclinal approach.

This letter describes the improved and efficient enantioselective synthesis of natural striatenic acid, isolated from Cheilolejeunea serpentina, and its methyl ester starting from a readily available enantiopure building block.

An enantioselective synthesis of (+)-ricciocarpin A is described starting from (+)-karahana lactone as an enantiopure building block. This synthesis involves a stereofacially directed diastereoselective hydroboration for the installation of the required stereogenic center, and the efficient conversion of an intermediate hydroxyaldehyde to the one-carbon homologated cyanide, using the mild formation of a cyanohydrin followed by an one-pot two-step Barton-McCombie double deoxygenation sequence of the hydroxyl moieties.

A short and efficient stereoselective synthesis of (±)-iso-norpatchoulenol 3 involving, as a key step, the intramolecular trapping of a vinyl carbanion is described. The new compound has a weak characteristic odor of patchouli.

Two new diterpenoids with the furanoid clerodane and dinorlabdane carbon skeletons, termed respectively (+)-7α-acetoxybacchotricuneatin D and (−)-3β-hydroxy-15,16-dinorlabd-8(17)-ene-13-one, were isolated from copaiba oil and their structures were elucidated by NMR spectroscopy.

The primordial influence of the ring size in the Lewis acid-promoted reaction of sterically unhindered isocyclic allylsilanes with 3-butyn-2-one is reported. In all the cases, the classical Sakurai-Hosomi reaction is, for the most part or fully, suppressed. With cyclohexanic frameworks, allyltrimethylsilanes like 1a-c afford mainly or solely H-ene components. This chemoselectivity is quite different from the one of cyclopentanic core compounds 1d-f which act primarily as [2 + 2] cycloaddition agents at the expense of the H-ene products procedure. Furthermore, the regioselectivity of the H-ene products formation is opposite for the two skeletons. Using Me 2 AlCl, the [2 + 2] cyloaddition of five carbon atoms isocyclic allylsilanes proceeds with complete chemoselectivity and provides an efficient synthesis of functionalized bicyclo [3. 2. 0] heptenes.

The reaction of diversely substituted α-cyclopropylketones with allyltrimethylsilane in the presence of titanium tetrachloride has been studied. The products formation is explained by the intervention of a cyclopropycarbinyl transient cation formed after a first 1,2-addition on the carbonyl. With regard to the structure of the starting compounds, this intermediate reacts with a second molecule of allylsilane, either by a bimolecular addition on the carbocycle, or by the direct attack on the carbon bearing the formal positive charge yielding diallyl and functionalised cyclohexane derivatives. A general mechanism is proposed.

NMR experiments unequivocally show that the by-product obtained from the ZnI 2 -promoted reaction of an allyltrimethylsilane with 3-butyn-2-one is a [2+2] cycloaddition compound. This fact corroborates our previously described assignment. In the experimental conditions used, the reaction occurs without 1,2-silyl shift.

Reaction of subtituted methylenecyclopropyl ketones with allyltrimethylsilane affords functionalized methylene or alkylidenecyclopentanes in good yield via a TiCl 4 mediated cleavage of the carbocycle followed by a [3+2] cycloaddition of the resultant 1,3-zwitterion with allyltrimethylsilane which acts as the 1,2-partner.

NMR experiments unequivocally show that the by-product obtained from the ZnI 2 -promoted reaction of an allyltrimethylsilane with 3-butyn-2-one is a [2+2] cycloaddition compound. This fact corroborates our previously described assignment. In the experimental conditions used, the reaction occurs without 1,2-silyl shift.

Reaction of subtituted methylenecyclopropyl ketones with allyltrimethylsilane affords functionalized methylene or alkylidenecyclopentanes in good yield via a TiCl 4 mediated cleavage of the carbocycle followed by a [3+2] cycloaddition of the resultant 1,3-zwitterion with allyltrimethylsilane which acts as the 1,2-partner.

An efficient one-pot synthesis of useful allylic hydroxymethyl methylenecycloalkane building blocks was achieved by a controlled H-ene / protodesilylation sequence using two different Lewis acids (Me2AlCl / SnCl4) and starting from readily available isocyclic allylsilanes.

The primordial influence of the ring size in the Lewis acid-promoted reaction of sterically unhindered isocyclic allylsilanes with 3-butyn-2-one is reported. In all the cases, the classical Sakurai-Hosomi reaction is, for the most part or fully, suppressed. With cyclohexanic frameworks, allyltrimethylsilanes like 1a-c afford mainly or solely H-ene components. This chemoselectivity is quite different from the one of cyclopentanic core compounds 1d-f which act primarily as [2 + 2] cycloaddition agents at the expense of the H-ene products procedure. Furthermore, the regioselectivity of the H-ene products formation is opposite for the two skeletons. Using Me 2 AlCl, the [2 + 2] cyloaddition of five carbon atoms isocyclic allylsilanes proceeds with complete chemoselectivity and provides an efficient synthesis of functionalized bicyclo [3. 2. 0] heptenes.

An efficient enantioselective synthesis of fully-oxygen, ated Taxol® A-ring subunit has been achieved using (-)-karahana lactone, (-)-2, as an enantiopure starting building-block and a diastereoselective allylic hydroxylation as the key step.

A new diterpenoid, (−)-15,16-dinorlabd-8 (17)-en-3 β ,13-diol was isolated from copaiba oil and its structure elucidated by NMR spectroscopy. In addition, the two structurally known cleroda-3,13-dien-15-ol (kolavenol) and labda-8 (17),13 ( E )-dien-15-ol (9,10- anti -copalol) were also identified for the first time in the product.

Starting from both enantiomers of a readily available building block, a straightforward enantioselective approach to constrained 3'-methyl-2',3'-alpha-oxirane-fused and 3'-methyl-3',4'-alpha-oxirane-fused carbanucleosides bearing different purine base analogues is described. The title compounds were evaluated as potential antiviral agents against important viruses. None of the new compounds had significant antiviral activity at a concentration of 100 microg/mL, which was the highest concentration tested.