对映体纯1-甲基-7-氧杂双环[2.2.1]庚烷-2-酮的制备

1-甲基 - 7-氧杂双环 [2 .2 .1 ]庚烷 - 2 -酮 ( 1 )是萜类天然产物全合成中的重要中间体 ,能被广泛地应用于多种桉烷 ( Eudesmane)、沉香呋喃 ( Agarofuran)和降胡萝卜素 ( Norcarotenoids)等倍半萜天然产物的全合成[1,2 ] .我们以对映体纯化合物 1为原料 ,实现这类天然产物的不对称全合成 [3～ 6 ] .消旋的化合物 (± ) - 1可以 2 -甲基呋喃和 2 -氯丙烯腈为原料 ,经 3步反应得到 [2 ] .但对映体纯化合物 1的制备尚未见报道 .本文用化学拆分方法 ,成功地制备了对映体纯的 ( + ) - 1和 ( - ) - 1 ,并确定了其绝对构型 .1　结果与讨论为减…     

Preparation of single-enantiomer semiochemicals using 2-methoxy-2-(1-naphthyl)propionic acid and 2-methoxy-2-(9-phenanthryl)propionic acid

Enantioresolution of 3-octanol, 6-methyl-5-hepten-2-ol (sulcatol), and 1-octen-3-ol was conducted using (S)-(+)-2-methoxy-2-(1-naphthyl)propionic acid (MαNP acid) and (S)-(+)-2-methoxy-2-(9-phenanthryl)propionic acid (M9PP acid). In each case, the diastereomeric esters obtained were readily separated by HPLC. The stereochemistry of the esters could be assigned from their respective ¹H NMR analyses. Solvolyses of the esters gave enantiopure alcohols and acids. MαNP and M9PP acids displayed almost equivalent properties in ¹H NMR anisotropy. The chiral resolving ability of M9PP acid was slightly superior to that of MαNP acid in HPLC.     

The synthesis of some optically active C-methylated 2-oxohexamethyleneimines

Three new, optically active, methyl-substituted 2-oxohexamethyleneimines were prepared by cyclization of the respective optically active C-methylated 6-aminohexanoic acids. The active forms of the amino acids used for the preparation of (?)-3-methyl-2-oxohexamethyleneimine and (?)-7-methyl-2-oxohexamethyleneimine were obtained by resolution of their diastereomeric quinine salts. s-(+)-5-methyl-2-oxohexamethyleneimine was synthesized without racemization from optically pure 2-isopropylidene-5-methyleyclohexanone (pulegone).     

Asymmetric synthesis of alpha,alpha-disubstituted alpha-amino acids using (S,S)-cyclohexane-1,2-diol as a chiral auxiliary

Diastereoselective alkylation of ethyl 2-methyl- and/or 2-ethylacetoacetates using the (S,S)-cyclohexane-1,2-diol as an acetal chiral auxiliary afforded enol ethers (2a-f and 5a-f) of 92->95% de in 31-70% yields. Removal of the cyclohexane-1,2-diol with BF(3)-OEt(2) afforded beta-keto esters (3 and 6) bearing a chiral quaternary carbon. The beta-keto esters could be easily converted into optically active alpha-methylated and/or alpha-ethylated alpha,alpha-disubstituted amino acids (12 and 13) in 21-99% yields using Schmidt rearrangement.     

R(-)四氢噻唑-2-硫酮-4-羧酸对D,L-氨基酸酯拆分的研究

以新手性拆分试剂R(-)四氢噻唑-2-硫酮-4-羧酸[简称R(-)TTCA]对D,L-氨基酸酯进行手性拆分,分别得到(R)TTCA氨基酸酯盐1a_1f([α]_D²⁰＝-30.40°～-42.70°)及光学活性氨基酸酯2a-2f,其光学纯度为35.4%～75.8%.由1a_1f在碱存在下分解出2a-2f的对映体3a-3f,光学纯度为39.50%～69.10%.用半经验的量子化学PM3方法研究了氨基的碱性、中间产物铵盐生成热和稳定性.     

Cationic and free-radical polymerization of optically active 1-olefins

The AlCl₃-initiated cationic polymerization of optically active 1-olefins yields polymers of varying optical rotatory power. Polymers of (+)-3-methyl-1-pentene and (?)-4-methyl-1-hexene prepared between ?78 and ?55°C. in CH₂Cl₂ or n-heptane are almost completely optically inactive. Under identical reaction conditions (+)-5-methyl-1-heptene gives polymers of significant optical rotatory power. Alternating SO₂copolymers of the same olefins, formed in reactions which proceed through free-radical intermediates, yield optically active products with specific rotations similar to those of low molecular weight analogs. These results are consistent with a cationic polymerization mechanism in which the growing chain undergoes intramolecular hydride shift and the asymmetric carbon atoms are converted into carbonium ions. The data also provide evidence for the lack of rearrangement in free-radical polymerization. By comparing the specific rotations of the cationic and free-radical polymers, the extent of rearrangement during cationic polymerization can be estimated. The calculations show that the 1,2-polymer in cationic poly-3-methyl-1-pentene is less than 2%, the sum of 1,2- and 1,3-polymer in cationic poly-4-methyl-1-hexene is less than 4%, and the sum of 1,2-, 1,3-, and 1,4-polymer in cationic poly-5-methyl-1-heptene is 14–20%.     

(-)-(R)- and (+)-(S)-Carvone in the Synthesis of Optically Active Acetylenic Alcohols,Ethers, and Dichlorosilyl Derivatives

Reaction of butyllithium with acetylene and 1-hexyne gave the corresponding lithium acetylides which reacted with (-)-(R)- and (+)-(S-carvone in a stereospecific fashion to give lithium (1-ethynyl- or 1-hexynyl)-5-isopropenyl-2-methyl-2-cyclohexenolates. Hydrolysis of the latter gave individual optically active tertiary terpene alcohols having both acetylenic and p-menthene fragment. Their treatment with methyl iodide in the presence of hexamethylphosphoric triamide afforded the corresponding methyl ethers. The reaction of 3-ethynyl-5-isopropenyl-3-methoxy-2-methylcyclohexene with butyllithium and trichloro(vinyl)silane yielded optically active dichlorosilyl-containing acetylenic compounds.     

Asymmetric [2,3]Wittig sigmatropic rearrangement involving a chiral azaenolate as the migrating terminus. A simple synthesis of (+)-verrucarinolactone

The diastereo- and/or enantioselection are described in the title rearrangement of the chiral 2-(2-alkenyloxy)methyl 2-oxazolines which eventually provides optically active -hydroxy, γ,δ- unsaturated esters and (+)-verrucarinolactone.     

Synthesis of poly(vinylamine) containing asymmetric nucleic acid base derivatives as grafted pendants

The preparations of new model polymers of polynucleotides with stereoregular poly(vinylamine) (PVAm) backbones and an optically active nucleic acid base derivative as a pending side chain are described. The grafting of (±)-, (+)-, and (?)-2-(thymin-1-yl) propionic acid to linear PVAm prepared either by hydrolysis of poly(vinyl acetamide) or poly(vinyl-t-butyl carbamate) has proven to be more difficult than the case of polyethyleneimine. This may be due to a combination of the low solubility and steric factors of PVAm. PVAm formed a complex with oximes such as ethyl-2-hydroxyimino cyanoacetate (EHICA), which activates the amino group of PVAm; it became soluble in polar solvents and gave higher percent graft. These carboxylic acid derivatives were grafted onto PVAm through amide bonds by direct coupling with sulfonic acid esters of hydroxybenzotriazoles to give optically active graft polymers. These coupling agents were found to be much superior reagents than DEPC regarding racemization. The related monomer and dimer model compounds were also prepared by the same method from 3-aminopentane and (?)-, (+)-, and meso-2,4-diaminopentane, respectively. The dimer models were separated and purified by HPLC to give models for isotactic, heterotactic, and syndiotactic polymer models. The enantiomeric purity of the optically active monomer model was determined by 360-MHz NMR spectroscopy using optically active shift reagents.     

High-performance liquid chromatographic separation of racemic and diastereomeric mixtures of 2,4-pentadienoate-iron tricarbonyl derivatives

beta-Cyclodextrin chiral stationary phase facilitates the chiral separation of the (+/-)-methyl-5-formyl-2,4-pentadienoate-iron tricarbonyl (1) racemic mixture. The separation of oxazolidine derivatives 2 and 3 diastereomers were achieved with a C18 column but the compounds underwent in-column hydrolysis to give (-)- and (+)-1, respectively. This hydrolysis was exploited for the determination of 2 and 3 by the beta-cyclodextrin column, namely 2 and 3 were initially and completely hydrolyzed in the column to give (-)- and (+)-1 and this racemic mixture was then separated by this chiral column.     

Configurational studies on 2-[∝-(2-ethoxyphenoxy)benzyl] morpholine fce 20124

The relative configuration of the two diastereoisomers of (±)2-[?-(2-ethoxyphenoxy)benzyl] morpholine is determined by a synthesis involving regio and stereo specific reactions. (RS,RS) diastereoisomer FCE 20124 was separated into its (+) and (-) enantiomers both by crystallization of the optically active mandelate salt and by a multi-step synthesis from (+)-(2S,3R)-3-phenylglycidic acid.     

Total Synthesis and Electrophysiological Properties of Natural (−)-Perhydrohistrionicotoxin,its Unnatural (+)-Antipode and their 2-Depentyl Analogs

Natural (?)-perhydrohistrionicotoxin ( 6a ), its unnatural (+)-antipode 6b , (?)-2-depentylperhydrohistrionicotoxin ( 7a ) and its (+)-antipode 7b have been prepared and characterized. Kishi's lactam 8 reacted with optically active iso-cyanates, and the mixture of diastereomeric carbamates so obtained was separated and hydrolyzed yielding the optical antipodes of Kishi's lactam in optically pure form. Reduction with LiAlH₄ yielded the optically active 2-depentyl analogs, while another sequence already developed in the racemic series afforded the natural toxin and its (+)-antipode. Some electrophysiological properties of these compounds are presented.     

Optically active antifungal azoles. IX. An alternative synthetic route for 2-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4- triazol-1-yl)propyl]-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]- 3(2H,4H)-1,2,4-triazolone and its analogs

A new route for the synthesis of the optically active antifungal azole TAK-187, 2-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-tria zol-1- yl)propyl]-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-3(2H,4H)-1,2,4 - triazolone, was established. The key synthetic intermediate, 2-[(1R)-2-(2,4-difluorophenyl)-2-oxo-1-methylethyl]-4-[4-(2,2,3,3- tetrafluoropropoxy)phenyl]-3(2H,4H)-1,2,4-triazolone (8), was prepared starting from the esters (11a, b) of (S)-lactic acid in a stereocontrolled manner. This optically active propiophenone derivative 8 was converted to the one carbon-elongated (1R,2S)-diol 7, which was then reacted with 1H-1,2,4-triazole to yield TAK-187. This newly developed route was applied to the synthesis of the analogs (25a, b--28a, b) containing an imidazolone or imidazolidinone nucleus.     

Synthesis and polymerization of (R)-(+)-2-methyl-2-ethyl-3-propiothiolactone

(R)-(+)-2-Methyl-2-ethyl-3-propiothiolactone was synthesized by debenzylation and cyclization of (?)-2-methyl-2-ethyl-3-benzylmercaptopropionyl chloride under the conditions of Friedel-Crafts synthesis, and by dehydration of (R)-(+)-2-methyl-2-ethyl-3-mercaptopropionic acid with dicyclohexyl carbodiimide. The configuration of the (+)-propiothiolactone was determined by chemical interconversion with (?)-2-methyl-2-ethylsuccinic acid, the absolute configuration of which is known to be (R). The polymerization of (R)-(+)-2-methyl-2-ethyl-3-propiothiolactone was performed in bulk with tetrabutylammonium versatate as catalyst. The specific rotation of the polymer ([α]_D +151.7°) compared with the rotation of the low molecular weight model compound (R)-(+)-2-methyl-2-ethyl-3-acetylmercapto-thiolpropionic acid methyl ester ([α]D +55.0°) shows a significant enhancement, thus suggesting the possibility of the presence of rigid conformations in polymer chain.     

Synthesis,separation, and resolution of cis- and trans-3-ethylproline

The synthesis, separation, and optical resolution of cis- and trans-3-ethylproline are described. Two different approaches were employed: (1) The Michael addition reaction of 2-pentenal with diethyl-N-carbobenzyloxyaminomalonate gave the intermediate 3-ethyl-5-hydroxy-N-benzyloxypyrrolidine. Hydrogenolysis of this intermediate followed by acid hydrolysis gave a mixture of cis- and trans-3-ethylproline. Separation of the isomers was accomplished by selective saponification of N-(p-toluenesulfonyl)-cis- and trans-3-ethylproline methyl esters using 0.25N methanolic sodium hydroxide. (2) The Michael condensation of diethyl acetamidomalonate with 2-pentenoic acid ethyl ether produced the intermediate 5,5-bis(ethoxycarbonyl)-4-ethylpyrrolidine. Partial saponification followed by decarboxylation afforded a mixture of cis- and trans-isomers of ethyl-3-ethylpyroglutamate. The diastereoisomers were separated using low temperature fractional crystallization. Reduction of these isomers and tosylation in situ afforded the corresponding N-(p-toluenesulfonyl)-cis- and trans-3-ethylprolinols. Chromic acid oxidation gave N-(p-toluenesulfonyl)-cis- and trans-3-ethylproline. Reaction of these tosylates with 30% hydrogen bromide in acetic acid gave cis- and trans-3-ethylproline. Both optically active isomers of D(+)-and L(-)-trans-3-ethylproline were successfully resolved using (+)-dibenzoyl-D -tartaric acid and (-)-dibenzoyl-L -tartaric acid as resolving agents. The absolute configurations of the optically active isomers were determined by circular dichroism spectroscopy.     

3,4-dihydro-6,7-dimethoxy-4-methyl-3-oxo-qinoxaline-2-carbonyl azide as a highly sensitive fluorescence derivatization reagent for primary,secondary and tertiary alcohols in high-performance liquid chromatography

3,4-Dhydro-6,7-dimethoxy-4-methyl-3-oxo-quinoxaline-2-carbonyl azide is a highly senstive fluorescence derivatization reagent for primary, secondary and tertiary alcohols for high-performance liquid chromatography. Reaction conditions are optimized with benzyl alcohol, n-hexanol, cyclohexanol and 2-methyl-2-butanol. The reagent reacts with the alcohols in benzene to produce the corresponding fluorescent carbamic acid esters, which can be separated on a reversed-phase column YMC Pack C₈ with aqueous methanol as eluent. the detection limits for the alchols are 2–5 fmol per 10-μl njection. The reagent also reacts with hydroxysteroids with primary, secondary and/or tertiary alcoholic group(s) to form fluorescent derivatives. Hydroxycarboxylic acids and phenols do not give any chromatographic peaks.     

A simple synthesis of (S)-(+)-sulcatol,the pheromone of gnathotrichus retusus, employing baker's yeast for asymmetric reduction

Ethyl (5)-3-hydroxybutanoate of 87% optical purity was obtained by the yeast reduction of ethyl acetoacetatc and was converted into 85–87% optically pure (S)-(+)-sulcatol (6-methyl-5-hepten-2-ol) by a 5-step sequence in 73% overall yield.     

endo-1,4,5,6,7,7-hexachlorobicyclo[2.2.1]hept-5-ene-2-carboxylic acid, a superior resolving agent for the high-performance liquid chromatographic separation of enantiomers of hydroxylated derivatives of two azaaromatic hydrocarbons

The high-performance liquid chromatographic (HPLC) separation of enantiomers of oxide and hydroxy derivatives of dibenz[a,j]acridine and 7-methylbenz[c]acridine was investigated on a chiral stationary phase chromatography column using commercially available columns. In most cases either poor or no separation of enantiomers was achieved. Normal-phase separation of diastereoisomeric ester derivatives of the hydroxy compounds, prepared from commercially available (-)-menthoxyacetic acid or (+)-alpha-methoxy-alpha-(trifluoromethyl)phenylacetic acid, was investigated. No separation of the diastereoisomeric esters of trans-3,4-dihydroxy-3,4-dihydrodibenz[a,j]acridine was observed. However, diastereoisomeric esters prepared from (+)-endo-1,4,5,6,7,7-hexachlorobicyclo[2.2.1]hept-5-ene-2-carboxyl ic acid [(+)-HCA] were easily separated. Using the three chiral acids, diastereoisomers were prepared from sixteen hydroxy derivatives of dibenz[a,j]acridine and 7-methylbenz[c]acridine. (+)-HCA esters gave good to excellent HPLC separations which were superior to those achieved using other chiral acids in most cases. The enantiomeric composition of trans-3,4-dihydroxy-3,4-dihydrodibenz[a,j]acridine formed as a major rodent liver microsomal metabolite of dibenz[a,j]acridine was determined using (+)-HCA.     

A novel synthesis, including asymmetric synthesis, of α-quaternary α-amino acid methyl esters from ketones via sulfinyloxiranes

Sulfinyloxiranes were synthesized from ketones and chloromethyl p-tolyl sulfoxide in two steps in almost quantitative yields. The sulfinyloxiranes were treated with NaN₃ in the presence of NH₄Cl to afford α-azido aldehydes, which were oxidized with iodine in the presence of KOH in methanol to give α-azido methyl esters in good overall yields. Catalytic hydrogenation of the α-azido esters afforded α-quaternary α-amino acid methyl esters in quantitative yields. Starting from β-tetralone and optically pure (R)-chloromethyl p-tolyl sulfoxide, an asymmetric synthesis of optically pure (R)-(+)-methyl 2-aminotetraline-2-carboxylate was realized in good overall yields.     

Gas chromatographic determination of the configuration of isovaline in antiamoebin,samarosporin (emerimicin IV), stilbellin,suzukacillins and trichotoxins

Summary The D-(resp. R) configuration of isovaline (=2-ethylalanine) was proved for the peptide antibiotics antiamoebin, Tü 165 (CBS 382.62), stilbellin, samarosporin (=emerimicin IV), suzukacillin B (A), trichotoxin A-40 and A-50. This contradicts the previously reported L-configuration for isovaline in antiamoebin and emerimicin IV. The configuration was determined by GC of the N-trifluoroacetyl-isovaline n-propyl ester on glass capillary columns coated with the chiral stationary phase N-propionyl-L-valine tert.-butylamide polysiloxane (Chirasil Val). The D-configuration of the isovaline from trichotoxin A-40 was also established independently using GC of N-pentafluoro-propionyl-isovaline (+)-3-methyl-2-butyl esters on glass capillary columns coated with OV 17.