Heterotricyclodecane XX (+)-(1S, 3S, 6S, 8S)- und (−)-(1R, 3R, 6R, 8R)-2, 7-Dioxa-twista-4,9-dien

(+)-(1S, 3S, 6S, 8S)- and (?)-(1R, 3R, 6R, 8R)-2,7-dioxa-twista-4,9-diene. A synthesis and the determination of the sense of chirality of (+)-(1S, 3S, 6S, 8S)- and (?)-(1R, 3R, 6R, 8R)-2,7-dioxa-twista-4,9-diene ((+)- 5 and (?)- 5 , respectively) is described.     

(+)-(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.     

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.     

A Convenient Stereoselective Synthesis of (1R,2S,3R,4S)-3-(Neopentyloxy)isoborneol

A convenient preparation of (1R,2S,3R,4S)-3-(neopentyloxy)isoborneol (= (1R,2S,3R,4S)-3-(2,2-dimethyl-propoxy)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol; 1a ), a valuable chiral auxiliary, is described. The synthesis involves six steps starting from the readily available camphorquinone ( 5 ) and gives 1a in 48% overall yield. The key step is the chemoselective hydrolysis of the less hindered 1,3-dioxolane moiety in the camphorquinone di-acetal 4 .     

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.     

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%.     

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).     

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.     

Synthesis of (-)-(S)-3-sec-butyl- and (+)-(S)-5-sec-butyl-2(1H)-pyridinone

Optically active (+)-(S)-5-sec-butyl- and (-)-(S)-3-sec-butyl-2(1H)-pyridinone are synthesized and the relationship between optical activity and minimum optical purity of the latter is determined.     

Asymmetric radical cyclization of (2S,3S)-2,3-butanediyl, (2S,4S)-2,4-pentanediyl,and (2S,5S)-2,5-hexanediyl bis(4-vinylbenzoate)s as a model reaction for asymmetric cyclocopolymerization

The asymmetric cyclocopolymerization of bis(4-vinylbezoate) of a chiral diol with styrene is a promising method for the preparation of optically active polystyrene derivatives because of main-chain chirality. However, the mechanism for chirality induction from the chiral diol to the main chain is still unknown. To clarify the chirality induction mechanism, we carried out the radical cyclizations of (2S,3S)-2,3-butanediyl bis(4-vinylbenzoate), (2S,4S)-2,4-pentanediyl bis(4-vinylbenzoate), and (2S,5S)-2,5-hexanediyl bis(4-vinylbenzoate) with tri-n-butyltin hydride or allyltri-n-butyltin as a chain-transfer reagent as model reactions for asymmetric cyclocopolymerization. The absolute configuration was determined with single-crystal X-ray crystallography and a circular dichroism exciton chirality method. The distribution of the stereoisomer showed (R)-configuration selectivity (21–34% diastereomeric excess) in the intramolecular cyclization and an extremely low extent (<1%) of the (S,S)-cyclized product among the four stereoisomers. Therefore, chirality induction is caused by the selective inhibition of the (S,S)-racemo configuration. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4671–4681, 2004     

Synthesis and study of (2S,4S)-4-arylamino-2-carboxy-5-pyrrolidones

(2S,4S)-4-Arylamino-2-carboxy-5-pyrrolidones were prepared by hydrolysis of dimethyl (2S,4S)-4-arylamino-N-phthaloylglutamates. The protonation constants of the arylamino group in the synthesized compounds were determined. The pyrrolidone ring is stable in acidic or neutral solutions. The relative stability of the pyrrolidone ring in alkaline solutions was studied by IR spectroscopy.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2087–2090, December, 1993.     

Synthesis of derivatives of (S)-2-alkanols, components of pheromones ofDrosophila mulleri andRhyzopertha dominica, from (S)-(+)-3,7-dimethylocta-1,6-diene

Effective routes for the synthesis of (S)-2-acetoxytridecane, the sex pheromone of the fruit flyDrosophila mulleri, and (S)-1-methylbutyl 2-methyl- and 2,4-dimethylpent-2E-enoates, components of the aggregation pheromone of the lesser grain borerRhyzopertha dominica, were developed on the basis of (S)-4-methylhex-5-en-1-yl tosylate accessible from (S)-(+)-dihydromyreene. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1929–1931, November, 2000.     

Absolute Conformation and Configuration of (2S, 3S)-3-Acetoxy-5-(dimethylaminoethyl)-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one Chloride (Dilthiazem Hydrochloride)

Resolution of racemic cis-3-(2-aminophenylthio)-2-hydroxy-3-(4-methoxyphenyl) propionic acid ( 2 ) via the cinchonidine salt 3 , and brucine salt 4 , isolation of the calcium salts (+)- and (?)- 5 , as well as their cyclization to enantiomeric 1,5-benzothiazepines (+)- and (?)- 1 , are described. X-Ray single-crystal analysis reveals (2S, 3S) absolute configuration of (+)- 1 on the basis of tentative comparison of CD data with those for the 1,4-benzodiazepine derivative (+)- 8 of known absolute configuration.     

Crystal Structure and Absolute Configuration of (+)-(1S, 2R)-5, 6-Dimethylidene-2exo-norbornyl-exo-irontricarbonyl p-Bromobenzoate

The title complex (+)- 13x has been prepared in an enantiomerically pure form. Its absolute configuration has been determined by single-crystal X-ray diffraction and has been correlated chemically to that of the 5, 6-dimethylidene-2-norbornyl derivatives (—)- 1 , (—)- 2 , (—)- 3 and to (—)-(1S, 2R)-benzonorborn-5-en-2-yl acetate (s. Scheme 1), whose configuration was deduced by indirect techniques. A critical analysis of the chiroptical properties of the exocyclic dienes 1–3 is now possible. These compounds are limiting systems for the application of the allylic axial chirality rule, the generalized octant rule and the symmetry rule for βγ-unsaturated ketones.     

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.     

Prostaglandin chemistry—V : Synthesis of new prostaglandin synthons; 4(R)-(+)- and 4(S)-(−)-t-butyldimethylsiloxycyclopent-2-en-1-one

Optically active prostaglandin intermediates, 4(R)-(+)- and 4(S)-(?)-hydroxycyclopent-2-en-1-one derivatives, were synthesized from 3(R),5(R)-diacetoxycyclopent-1-ene, 3(R)-acetoxy-5(R)-hydroxycyclopent-1-ene and 3(S),5(S)-dihydroxycyclopent-1-ene obtained by microbiological hydrolysis of 3,5-diacetoxycyclopent-1-ene. The absolute configurations of all these compounds were determined by the exciton chirality method and the induced CD method. The optical purities were determined by NMR measurements of the diastereomeric esters of a versatile optically pure acid, (+)-α-methoxy-α-trifluoromethylphenylacetic acid.     

C45- and C50-Carotehoids. Part 8. Synthesis of (all-E,2S,2′S)-bacterioruberin, (all-E,2S,2′S)-monoanhydrobacterioruberin, (all-E,2S,2′S)-bisanhydrobacterioruberin, (all- E,2R,2′R)-3,4,3′,4′-tetrahydrobisanhydro- bacterioruberin,and (all-E,S)-2-isopentenyl-3,4-dehydrorhodopin

Starting from (R)-3-hydroxybutyric acid ((R)- 10 ) the C₄₅- and C₅₀-carotenoids (all-E,2S,2′S)-bacterioruberm ( 1 ), (all-E,2S,2′S)-monoanhydrobacterioruberin ( 2 ), (all-E,2S,2′S)-bisanhydrobacterioruberin ( 3 ), (all-E,2R,2′R)-3,4,3′,4′-tetrahydrobisanhydrobacterioruberin ( 5 ), and (all-E,S)-2-isopentenyl-3,4-dehydrorhodopin ( 6 ) were synthesized. By comparison of the chiroptical data of the natural and the synthetic compounds, the (2S)- and (2′S)-configuration of the natural products 1–3 and 6 was established.     

Synthesis and analytical properties of (S)-(+)-2-methoxy-2-(9-phenanthryl)propionic acid

2-Methoxy-2-(9-phenanthryl)propionic acid was synthesized as a novel chiral resolving agent. The absolute configuration of (+)-2-methoxy-2-(9-phenanthryl)propionic acid was determined to be S by using X-ray structural analysis of the (1R,2S,5R)-menthyl ester. In the crystal, the methoxyl and carbonyl groups of the ester are in a syn-periplanar position. The syn-periplanar conformations of (1R,2S,5R)-menthyl esters were also observed by the NMR analyses in CDCl₃. The utility of (S)-(+)-2-methoxy-2-(9-phenanthryl)propionic acid was exemplified by the resolution of (±)-3-octanol.     

Über die Stereoselektivität der α-Alkylierung von (1R, 2S) (+)-cis-2-hydroxy-cyclohexancarbonsäureäthylester

The Stereoselectivity of the α-Alkylation of (+)-(1R, 2S)-cis-Ethyl-2-hydroxy-cyclohexanecarboxylate In continuation of our work on the stereoselectivity of the α-alkylation of β-hydroxyesters [1] [2], we studied this reaction with the title compound (+)- 2 . The latter was prepared through reduction of 1 with baker's yeast. Alkylation of the dianion of (+)- 2 furnished (?)- 4 in 72% chemical yield (Scheme 1) and with a stereoselectivity of 95%. Analogously, (?)- 7 was prepared with similar yields. Oxidation of (?)- 4 and (?)- 7 respectively furnished the ketones (?)- 6 (Scheme 3) and (?)- 8 (Scheme 4) respectively, each with about 76% enantiomeric excess (NMR.). It is noteworthy that yeast reduction of rac- 6 (Scheme 3) is completely enantioselective with respect to substrate and product and gives optically pure (?)- 4 in 10% yield, which was converted into optically pure (?)- 6 (Scheme 3). The alkylation of the dianionic intermediate shows a higher stereoselectivity (95%) from the pseudoequatorial side than that of 1-acetyl- or 1-cyano-4-t-butyl-cyclohexane (71% and 85%) [9] or that of ethyl 2-methyl-cyclohexanecarboxylate (82%). The stereochemical outcome of the above alkylation is comparable with that found in open chain examples [1] [2]. Finally (+)-(1R, 2S)- 2 was also alkylated with Wichterle's reagent to give (?)-(1S, 2S)- 9 in 64% yield. The latter was transformed into (?)-(S)- 10 and further into (?)-(S)- 11 (Scheme 5). (?)-(S)- 10 and (?)-(S)- 11 showed an e.e. of 76–78% (see also [11]). Comparison of these results with those in [11] confirmed our former stereochemical assignment concerning the alkylation step.     

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.