(+)-(1S, 3S, 6S, 8S)-und (−)-(1R, 3R, 6R, 8R)-4, 9-Twistadien: Synthese und Bestimmung der absoluten Konfiguration

(+)-(1S, 3S, 6S, 8S)-and (?)-(1R, 3R, 6R, 8R)-4, 9-Twistadiene: Synthesis and Absolute Configuration A synthesis and the determination of the absolute configuration of (+)-(1S, 3S, 6S, 8S)- and (?)-(1R, 3R, 6R, 8R)-4, 9-twistadiene ((+)- and (?)- 4 , respectively) is described. Their chiroptical properties are compared with those of saturated twistane ((+)- and (?)- 5 ) as well as with those of the unsaturated and saturated 2, 7-dioxatwistane analogs (+)- and (?)- 9 , and (+)- and (?)- 10 , respectively, which also are compounds of known absolute configurations.     

Synthèse énantiospécifique du (+)-(6S, 8R,E)-2,3-didéhydrononactate de méthyle

Enantiospecific Synthesis of (+)-(6S,8R,E)-Methyl 2,3-Didebydrononactate (+)-(6S,8R,E)-Methyl 2,3-didehydrononactate ( 7 ) has been synthesised from (?)-(3R)-methyl 3-hydroxy-butanoate with an enantiomeric excess ≥95%. The known stereoselective hydrogenation of 7 affords (?)-(2R,3R,6S,8R)-methyl nonactate ( 8 ) as the major isomer, a chiral synthon for the synthesis of nonactin.     

Synthesis of (+)-1,3:2,5-dianhydroviburnitol ((+)-(1R,2R,3S,5R,6S)-4,7-dioxatricyclo[3.2.1.03,6]octan-2-ol)

Epoxidation of (?)-(1R,2R,4R)-2-endo-cyano-7-oxabicyclo[2.2.1]hept-5-en-2-exo-yl acetate ((?)-5) followed by saponification afforded (+)-(1R,4R,5R,6R)-5,6-exo-epoxy-7-oxabicyclo[2.2.1]heptan-2-one ((+)-7). Reduction of (+)-7 with diisobutylaluminium hydride (DIBAH) gave (+)-1,3:2,5-dianhydroviburnitol ( = (+)-(1R,2R,3S,4R,6S)-4,7-dioxatricyclo[3.2.1.0^3,6]octan-2-ol; (+)-3). Hydride reductions of (±)-7 were less exo-face selective than reductions of bicyclo[2.2.1]heptan-2-one and its derivatives with NaBH₄, AlH₃, and LiAlH₄ probably because of smaller steric hindrance to endo-face hydride attack when C(5) and C(6) of the bicyclo-[2.2.1]heptan-2-one are part of an exo oxirane ring.     

Synthesis of (+)-(4S, 8R)hyphen;8hyphen;Epi- and (−)-(4R, 8S)-4-Epi-β-bisabolol

The first total enantioselective synthesis of (+)-(4S, 8R)-8-epi-β-bisabolol(+)- 1 and of (?)-(4R, 8 S )-4-epi-β-bisabolol ((?))? 1 ) is reported. The key step in the synthesis is the kinetic resolution of (±)? 5 by means of the Sharpless epoxidation yielding (?)- and (+}? 6 , respectively. Reduction of the epoxides with LiAlH₄ gave the diols (+)-and(?)? 7 which were transformed into (+)- and (?)? 8 , respectively, via the corresponding mesylate. Reaction of these epoxides with the Grignard reagent derived from homoprenylbromide, assisted by Li₂CuCl₄, finished the synthesis of the target compounds 1 with high diastereo- and enantioselectivity.     

Total Synthesis of (+)-(8S,13R)-Cyclocelabenzine

An asymmetric synthesis of the spermidine alkaloid (+)-cyclocelabenzine ( 1a ) and its (?)-(13S)-epimer 1b is described using optically active (+)-(3S)-3-amino-3-phenylpropionic acid as the chiral building block. The isoquinolin-1-one fragment 15 was synthesized by a modified Bischler-Napieralski reaction. The relative configuration of the (?)-isomer was determined by an X-ray crystal-structure analysis, which enabled us to determine the absolute configuration of natural (+)- 1a as (8S,13R).     

Synthèse énantiospécifique des acides (+)-(2R)- et (−)-(2S)-éthyl-6-dihydro-3,4-méthyl-2-oxo-4–2H pyranecarboxylique-5

Enantiospecific Synthesis of (+)-(2R)- and (?)-(2S)-6-Ethyl-3,4-dihydro-2-methyl-4-oxo-2H-pyran-5-carboxylic Acid The two enantiomers (?)-(2S)- and (+)-(2R)-6-ethyl-3,4-dihydro-2-methyl-4-oxo-2H-pyran-5-carboxylic acid ((S)- and (R)- 7 ) have been synthesized from (+)-(3S) and (?)-(3R)-3-hydroxybutanoates, respectively (Scheme 1). By reduction and decarboxylation, the tetrahydro-2H-pyranols (2R, 4R, 6S)- and (2S, 4S, 6R)- 13 , respectively, were obtained with an enantiomeric excess of ≥ 93%.     

Heterotricyclodecane VIII. (−)-(1S, 3R, 6R, 8R)-2, 7-Dioxaisotwistan und (−)-(1R, 3R, 6R, 8R)-2, 7-Dioxa-twistan; Synthese und Bestimmung der absoluten Konfiguration

A synthesis and the determination of the absolute configuration of (?)-(1S, 3R′ 6R, 8R)-2, 7-dioxa-isotwistane ( 13 ) and (?)-(1R, 3R, 6R, 8R)-2, 7-dioxa-twistane ( 14 ) is described. The results for 14 are compared with those for carboeyclic (+)-twistane ( 2 ) of known chirality.     

Synthesis of (R)- and (R)-4-methyl-6-2′-methylprop-1′-enyl-5,6-dihydro-2H-pyran (Nerol oxide) and Natural Occurrence of its Racemate

Following a known procedure, a mixture of (?)-(2S,3R)- and (+)-(2R,3R)-2,3-epoxy-citronellols ( 5 ) was prepared from (?)-(R)-linalool ( 3 ) via epoxy alcohol 4 and then reduced to (?)-(R)-3-hydroxy-citronellol ( 6 ). Sensitized photooxygenation of (?)-(R)-diol 6 led in part to (?)-(R)-triol 8 which was cyclodehydrated by dilute acid to a mixture of diastereoisomeric tetrahydropyran-4-ols 9 and 10 . Dehydration of hydroxy ethers 9 and 10 afforded (?)-(S)-nerol oxide ( 11 ) and (+)-(R)-nerol oxide ( 12 ), respectively, with an optical purity of 91%. Nerol oxide isolated from Bulgarian rose oil (0.038%) proved to be racemic. These results shed some light on the formation of nerol oxide in plants.     

Synthesis of (5R,8S,10R)-6-(Allyloxy)- and (5R,8S,10R)-6-(Propyloxy)ergolines from the 6-Methyl Precursors

Novel (5R,8S,10R)-6-(allyloxy)- and (5R,8S,10R)-6-(propyloxy)ergolines have been synthesized by use of a Meisenheimer [2,3]-sigmatropic rearrangement of a (5R,8S,10R)-6-allyl-ergoline N⁶-oxide as key step.     

Synthesis of(+)-(2S, 6S)-trans-α-Irone and of(-)-(2S, 6S)-trans-γ-Irone

A 3:1 mixture of (+)-(2S, 6S)-trans-α-irone ((+)-1) and (?)-(2S, 6S)-trans-γ-irone (?)-2) has been synthesized with ca. 70% e. e. by the ene reaction of (?)-(S)-3 and but-3-yn-2-one.     

Synthèse énantiospécifique du (−)-(1R, 3R, 5S)-diméthyl-1,3-dioxa-2,9-bicyclo[3.3.1]nonane

Enantiospecific Synthesis of (?)-(1R, 3R, 5S)-1,3-Dimethyl-2,9-dioxabicyclo[3.3.1]nonane The isomer (?)-(1R, 3R, 5S)-endo-1,3-dimethyl-2,9-dioxabicyclo[3.3.1]nonane ((1R, 3R, 5S)- 8 ) has been synthesized from (?)-(3R)-methyl 3-hydroxybutanoate. The key intermediate (3R, 5R)- 5 is proved to be a useful synthon for EPC syntheses.     

Circular Dichroism of Tricarbonyl(diene)iron Complexes. The Octant Rule Applied to Ketones Perturbed by Remote Fe(CO)3 Groups. Crystal Structure of (±)-Tricarbonyl[(1RS,4RS,5RS,6SR)-C5,6,C-η-(5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octanone)]iron

The preparation and the CD spectra of optically pure (+)-trans-μ-[(1R,4S,5S,6R,7R,8S)-C,5,6,C -η : C,7,8,C-η-(5,6,7,8-tetramethylidene-2-bicyclo [2.2.2]octanone)]bis(tricarbonyliron) ((+)- 7 ) and (+)-tricarbonyl[(1S,4S,5S,6R)-C-5,6,C-η-(5,6,7,8,-tetramethylidene-2-bicyclo[2.2.2]octanone)]iron ((+)- 8 ), and of its 3-deuterated derivatives (+)-trans-μ-[(1R,3R,4S,5S,6R,7R,8S)-C,5,6,C-η : C,7,8,C-η-5,6,7,8-tetramethylidene(3-D)-2-bicyclo[2.2.2]-(octanone)]bis(tricarbonyliron) ((+)- 11 ) and (+)-tricarbonyl[(1S,3R,4S,5S,6R)-C-5,6,C- η-(5,6,7,8-tetramethylidene(3-D)-2-bicyclo[2.2.2]octanone)]iron ((+)- 12 ) are reported. The chirality in (+)- 7 and (+)- 8 is due to the Fe(CO)₃ moieties uniquely. The signs of the Cotton effects observed for (+)- 7 and (+)- 8 obey the octant rule (ketone n→π*_CO transition). Optically pure (?)-3R-5,6,7,8-tetramethylidene(3-D)-2-bicyclo[2.2.2]octanone ((?)- 10 ) was prepared. Its CD spectrum showed an ‘anti-octant’ behaviour for the ketone n→π*_CO transition of the deuterium substituent. The CD spectra of the alcoholic derivatives (?)-trans-μ-[(1R,2R,4S, 5S,6R,7R,8S)-C,5,6,C-η : C,7,8,C- η-(5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octanol)]bis(tricarbonyliron) ((?)- 2 ) and (?)-tricarbonyl- [(1S,2R,4S,5S,6R)- C,5,6,C- η-(5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octanol)]iron ((?)- 3 ) and of the 3-denterated derivatives (?)- 5 and (?)- 6 are also reported. The CD spectra of the complexes (?)- 2 , (?)- 3 , (+)- 7 , and (+)- 8 were solvent and temperature dependent. The ‘endo’-configuration of the Fe(CO)₃ moiety in (±)- 8 was established by single-crystal X-ray diffraction.     

Stereoselective Conversion of Campholene- to Necrodane-Type Monoterpenes. Novel Access to (−)-(R,R)- and (R,S)-α-Necrodol and the Enantiomeric γ-Necrodols

Naturally occurring (?)-(R,R)-α-necrodol ((?)- 1 ) and its C(4)-epimer (?)- 2 are obtained in 84 and 44% yields, respectively, by lithium ethylenediamide (LEDA) treatment of the corresponding β-necrodols (?)- 3 and (?)- 4 (Scheme 1, Table), both readily available from (?)-campholenyl acetate ((?)- i ) by an efficient stereoselective synthesis. The thermodynamically preferred (?)-(R)-γ-necrodol ((?)- 5 ) becomes the major product (≥ 80% yield) after either prolonged treatment with LEDA or exposure of α- and β-necrodols to BF₃·Et₂O. In an alternative route, (+)- 5 is prepared starting from (+)-campholenal ((+)- ii ) via Pd-catalysed decarbonylation to (?)-(S)-1,4,5,5-tetramethylcyclopent-l-ene ((?)- 6 ) and subsequent application of an acid-catalysed CH₂O-addition/rearrangement sequence (Scheme 2).     

Synthese und Chiralität von (5R, 6R)-5,6-Dihydro-β, ψ-carotin-5,6-diol, (5R, 6R, 6′R)-5,6-Dihydro-β, ε-carotin-5,6-diol, (5S, 6R)-5,6-Epoxy-5,6-dihydro-β, ψ-carotin und (5S, 6R, 6′R)-5,6-Epoxy-5,6-dihydro-β,ε-carotin

Synthesis and Chirality of (5R, 6R)-5,6-Dihydro-β, ψ-carotene-5,6-diol, (5R, 6R, 6′R)-5,6-Dihydro-β, ε-carotene-5,6-diol, (5S, 6R)-5,6-Epoxy-5,6-dihydro-β,ψ-carotene and (5S, 6R, 6′R)-5,6-Epoxy-5,6-dihydro-β,ε-carotene Wittig-condensation of optically active azafrinal ( 1 ) with the phosphoranes 3 and 6 derived from all-(E)-ψ-ionol ( 2 ) and (+)-(R)-α-ionol ( 5 ) leads to the crystalline and optically active carotenoid diols 4 and 7 , respectively. The latter behave much more like carotene hydrocarbons despite the presence of two hydroxylfunctions. Conversion to the optically active epoxides 8 and 9 , respectively, is smoothly achieved by reaction with the sulfurane reagent of Martin [3]. These syntheses establish the absolute configurations of the title compounds since that of azafrin is known [2].     

Synthèse des (−)-(6R)-et(+)-(6S)-tétrahydro-6-[(Z)-pent-2-ényl]-2H-pyran-2-one,lactones de Jasminum grandiflorum L. et de Polianthes tuberosa L.

Synthesis of (?)-(6R)- and (+)-(6S)-Tetrahydro-6-[(Z)-pent-2-enyl]-2H-Pyran-2-one, lactones from Jasminum grandiflorum L. and from Polianthes tuberosa L. (?)-(2S)-Ethyl 2-hydroxyhexanedioate ((2S)- 2 ) was obtained by kinetic resolution of racemic ethyl 2-hydroxy-hexanedioate with baker's yeast. The key intermediates (+)-(5R)- and (?)-(5S)-ethyl 5,6-epoxyhexanoate ((5R)- and (5S)- 6 , resp.) are proved to be useful synthons for the total synthesis of chiral 6-alkyl-δ-lactones, as exemplified by the preparation of both enantiomers of jasmine lactone ((6R)- and (6S)- 10 , resp.).     

Neue Synthese von (−)-(R)-Cembren A,Synthese von (+)-(R)-Cembrenen und (+)-(S)-Cembren

Novel Synthesis of (?)-(R)-Cembrene A, Synthesis of (+)-(R)-Cembrenene and (+)-(S)-Cembrene A novel synthesis of (?)-(R)-cembrene A ((?)- 3 ) was developed using the Sharpless epoxidation for the introduction of the chiral center. Furthermore, the synthesis of (+)-(R)-cembrenene ((+)- 4 ) showed that this cembranoid must have the (R)-configuration and not, as previously reported, the (S)-configuration. Selective hydrogenation of (+)- 4 afforded (+)-(S)-cenibrene ((+)- 5 ).     

Synthesis of potential metabolites of the brain imaging agents methyl (1R,2S,3S,5S)-3-(4-Iodophenyl)-8-alkyl-8-azabicyclo[3.2.1]octane-2-carboxylate

The synthesis of potential hydroxy metabolites of the brain imaging agents methyl (1R,2S,3S,5S)-3-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate and methyl (1R,2S,3S,5S)-3-(4-iodophenyl)-8-(3-fluoropropyl)-8-azabicyclo[3.2.1]octane-2-carboxylate are reported. The nitration of iodophenyltropanes 1 or 2 with nitronium tetrafluoroborate afforded the nitro compounds 3 or 4 which were reduced with iron powder to the corresponding amino compounds 5 and 6 . The final hydroxylated products 7 and 8 were obtained via a modified Sandmeyer reaction.     

Stereochemische Korrelationen zwischen (2R,4′R,8′R)-α-Tocopherol, (25S,26)-Dihydroxycholecalciferol, (–)-(1S,5R)-Frontalin und (–)-(R)-Linalol

Stereochemical Correlations between (2R,4′R,8′R)-α-Tocopherol, (25S,26)-Dihydroxycholecalciferol, (–)-(1S,5R)-Frontalin and (–)-(R)-Linalol The optically active C₅- and C₄-building units 1 and 2 with their hydroxy group at a asymmetric C-atom were transformed to (–)-(1S,5R)-Frontalin ( 7 ) and (–)-(3R)-Linalol ( 8 ) respectively; 1 and 2 had been used earlier in the preparation of the chroman part of (2R,4′R,8′R)-α-Tocopherol ( 6a , vitamin E), and for introduction of the side chain in (25S,26)-Dihydroxycholecalciferol ((25S)- 4 ), a natural metabolite of Vitamin D₃. The stereochemical correlations resulting from these converions fit into a coherent picture with those correlations already known from literature and they confirm our earlier stereochemical assignments. A stereochemical assignment concerning the C(25)-epimers of 25,26-Dihydroxycholecalciferol that was in contrast to our findings and that initiated the conversion of 1 and 2 to 7 resp. 8 for additional stereochemical correlations has been corrected in the meantime by the authors [26].     

Stereospezifische Synthese von (+)-(3R, 4R)-4-Methyl-3-heptanol,das Enantiomere eines Pheromons des kleinen Ulmensplintkäfers (Scolytus multistriatus)

Stereospecific Synthesis of (+)-(3R, 4R)-4-Methyl-3-heptanol, the Enantiomer of a Pheromone of the Smaller European Elm Bark Beetle (Scolytus multistriatus) Reduction of 2 with actively fermenting baker's yeast gave (?) -3. Stereospecific alkylation [3] of (?) -3 with propyl iodide furnished ethyl (+)-(2R, 3R)-2-propyl-3-hydroxypentanoate ((+) -4 , 58%) which was converted to the tetrahydropyranyl ether (?) -5 , then the alcohol 6 , the p-toluenesulfonate 7 and the thiophenyl ether 8 to give the title compound (+) -1. The latter consisted of 97% of the threo- and 3% of the erythro-isomer. The above synthesis also correlates the absolute configuration of (?)-(R) -3 with that of (+)-(R)-citronellic acid (see [2]).     

Synthese von optisch aktiven,natürlichen Carotinoiden und strukturell verwandten Naturprodukten. V. Synthese von (3R, 3′R)-, (3S, 3′S)- und (3R,3′S; meso)-Zeaxanthin durch asymmetrische Hydroborierung. Ein neuer Zugang zu Optisch aktiven Carotinoidbausteinen. Vorläufige Mitteilung

Synthesis of Optically Active Natural Carotenoids and Structurally Related Compounds. V. Synthesis of (3R, 3′R)-, (3S, 3′S)- and (3R,3′S; meso)-zeaxanthin by Asymmetric Hydroboration. A New Approach to Optically Active Carotenoid Building Units The synthesis of (3R, 3′R)-, (3S, 3′S)- and (3R,3′S; meso)-zeaxanthin ( 1 ), ( 19 ) and ( 21 ) is reported utilizing asymmetric hydroboration as the key reaction. Thus, safranol isopropenylmethylether ( 4 ) is hydroborated with (+)- and (?)-(IPC)₂BH to give the optically pure key intermediates 5 and 7 resp., which are transformed into the above-mentioned C₄₀-compounds.