Synthesis and ring-opening polymerization of optically pure mesogenic malolactonates

Optically pure malolactonate monomers containing biphenyl mesogenic groups with either an ethylene or a hexamethylene spacer were prepared from optically pure malic acid and polymerized with alkylaluminoxane catalysts to form a series of new chiral side chain liquid-crystalline polymers, which contained the chiral centres in the backbone. The mesogenic malolactonate monomers were determined to be optically pure by ¹H NMR spectroscopy of the β-lactone complexed with a chiral europium shift reagent. Both the methylaluminoxane and isobutylaluminoxane catalysts gave polymers having bimodal molecular weight distributions, the latter catalyst yielded a larger amount of the higher molecular weight fraction than the former. The polymers showed high optical rotations, high degrees of isotactic stereoregularity, and enantiotropic liquid-crystalline properties, all of which were influenced by the molecular weight distribution. Copolymers of malolactonate monomers with different spacers were also prepared and characterized.     

A novel synthetic method for optically active terpenes by the ring-opening reaction of (R)-(+)-β-methyl-β-propiolactone

Optically active terpene such as (R)-(+)-citronellol, (R)-(+)-pulegone or (S)-ar-turmerone is prepared in high enantiomeric excess from an intermediate, (R)-(+)-citronellic acid or (S)-(+)-3-p-tolylbutyric acid, which is easily prepared by the Sn2 type of ring opening reaction of (R)-(+)-β-methyl-β-propiolactone with homoprenylmagnesium bromide in the presence of a copper(I) salt or di-p-tolylcuprate.     

Pd(II)‐catalyzed polymerization of optically active norbornene carboxylic acid esters

(?)‐(1S,2R)‐Norbornene‐2‐carboxylic acid alkyl esters (alkyl = Me, Bz, L ‐menthyl, or D ‐menthyl) were successfully prepared by the Diels–Alder reaction of cyclopentadiene with (R)‐(?)‐pantolactone‐O‐yl acrylate followed by epimerization and column chromatography. The enantiomeric excess was 99.9%. These monomers were polymerized by Pd(II)‐based catalysts, and high yields of the polymers were obtained. The methyl ester gave an optically active polymer of high optical rotation (monomer [α]_D = ?24.7, polymer [α]_D = ?98.5). This high rotation value of the polymer was attributed to the isotactic chain regulation of the polymer. This high rotation was not observed with methyl esters prepared by the transesterification of menthyl esters. The stereoregular polymer exhibited notable resonance peaks at 39 ppm in ¹³C NMR spectra. No crystallinity was observed. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 1263–1270, 2006     

Controlled ring-opening polymerization of cyclic esters with phosphoric acid as catalysts

(R)-(?)-1,1′-Binaphthyl-2,2′-diyl hydrogen phosphate (BPA) has been demonstrated as an efficient organocatalyst for controlled ring-opening homopolymerization of ε-caprolactone (ε-CL) and copolymerization of ε-CL with glycolide and lactide. High molar mass PCL with narrow molar mass distribution has also been synthesized from the bulk ring-opening polymerization (ROP) of ε-CL with BPA as catalysts; the highest molar mass of PCL is 4.35?×?10⁴ g/mol with polydispersity index of 1.20. The successful synthesis of high molar mass PCL is attributed to the bifunctional activation mechanism for the ROP of ε-CL catalyzed by BPA. More interestingly, ppm level of BPA is sufficient to catalyze controlled ROP of ε-CL.     

Terpenes in organic synthesis. 8. Synthesis of optically active (2R/S, 3S, 7R/S)-(-)-diprionyl acetate from (S)-(+)-3,7-dimethyl-1,6-octadiene

Conclusions A seven-stage synthesis has given optically active (2R/S, 3S, 7R/S)-2-acetoxy-3,7-dimethylpentadecane from the readily available (S)-(+)-3,7-dimethyl-1,6-octadiene, in an overall yield of 36%. The synthetic route utilizes all ten carbon atoms of the starting chiral diene.For previous communication, see [1].Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp. 1142–1146, May, 1988.     

(+)-Colletodiol : Synthesis from (S,S)-tartaric acid and (R)-3-hydroxy-butyric acid

E-(R)-5-Hydroxy-2-hexenoic acid (4) and the acetonide of E-(4R,5R,7R)-trihydroxy-2-octenoic acid (3) are joined to give, after deprotection, (+)-colletodiol (1). The syntheses of the two hydroxy-acids from poly-(R)-3-hydroxy-butanoate (PHB) and (?)-tartaric acid, respectively, are outlined.     

Enantioselective drug monitoring of (R)- and (S)- propranolol in human plasma via derivatization with optically active (R,R)-O,O-diacetyl tartaric acid anhydride

A sensitive high-performance liquid chromatographic method was developed for the stereoselective assay of (R)- and (S)-propranolol in human plasma. The method involves diethyl ether extraction of the drugs and a racemic internal standard, N-tert.-butylpropranolol, followed by derivatization of the compounds with the chiral reagent (R,R)-O,O-diacetyl tartaric acid anhydride. The resulting diastereomeric derivatives were separated isocratically on a reversed-phase column. Quantitation was achieved by the peak-height ratio method with reference to the internal standard. The assay was accurate and reproducible in the concentration range 1-100 ng of (R)- and (S)-propranolol per ml plasma, using fluorescence detection at lambda ex 290 nm and lambda em 335 nm. The applicability of this method was demonstrated for the determination of concentration-time profiles of propranolol enantiomers in the course of comparative pharmacokinetic studies.     

Total synthesis of (S)-(+)-curcudiol, and (S)-(+)- and (R)-(-)-curcuphenol.

A highly enantioselective synthesis of the versatile chiral synthons possessing one stereogenic center, (S)- and (R)-4-aryl-5-hydroxy-(2E)-pentenoate (3) was achieved based on the enzymatic reaction of (+/-)-3 with commercially available lipases MY-30 or OF-360 from Candida rugosa. Application of (S)-3 and (R)-3 to the total syntheses of(S)-curcuphenol (1), (S)-curcudiol (2), and (R)-curcuphenol (1), respectively, is described.     

(+)-(1S,2S,5R)-8-联苯薄荷醇的合成

以(R)-( )-pu legone为起始原料,经1,4-加成,还原两步反应合成了手性辅助试剂( )-(1S,2S,5R)-8-联苯薄荷醇及其差向异构体(-)-(1R,2S,5R)-8-联苯薄荷醇,总产率95%。其结构经1H NMR,13C NMR,IR,MS和X-射线衍射仪表征。     

Efficient preparation of highly optically active (S)-(-)-2,3-allenols and (R)-(+)-2,3-allenyl acetates by a clean novozym-435-catalyzed enzymatic separation of racemic 2,3-allenols

Novozym-435 has been found to be an effective biocatalyst for the kinetic resolution of a series of racemic 2,3-allenols, affording highly optically active (S)-(-)-2,3-allenols and (R)-(+)-2,3-allenyl acetates in high yields and with excellent ee values. The reaction of 3-(n-butyl)-3,4-pentadien-2-ol (1 a) was successfully performed on a 10 g scale to afford the corresponding (S)-(-)-2,3-allenol (1 a) and (R)-(+)-2,3-allenyl acetate (2 a) in synthetically useful amounts and with high ee values. The advantages of this reaction are the ready availability of the starting materials, high stereoselectivities for both (-)-2,3-allenols and (+)-2,3-allenyl acetates, the use of a relatively high substrate concentration, and a lower catalyst loading. The resulting (S)-(-)-2,3-allenol 1 a can be converted into the corresponding chiral 2,5-dihydrofuran and the vinylic epoxide.     

Living cationic ring-opening polymerization by water-stable initiator: synthesis of a well-defined optically active polythiourethane

Living cationic ring-opening polymerization under air and water was achieved using a well-defined water-resistant cationic initiator in dichloromethane without purification at ambient temperature.     

Chiral symmetric phosphoric acid esters as sources of optically active organophosphorus compounds

Chiral symmetric di- and trialkylphosphites, derivatives of (−)-borneol, (−)-menthol and (−)-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose, were studied as starting reagents for the preparation of chiral organophosphorus compounds. The reaction occurs by asymmetric induction at the α-carbon atom of substituted α-alkylphosphonates. The stereoselectivity of the reaction depends on the structure of the starting compounds and the reaction conditions. The configuration of the alkylphosphonates was established by NMR spectroscopy, by transformation into α-hydroxyalkylphosphonic acids and by X-ray crystal structure analysis.     

Chemistry of baker's yeast reduction products: Use of optically active (S)-(+)-1-(p-toluenesulfonyl)propan-2-ol and (S)-(+)-1-(phenylsulfonyl)propan-2-ol in synthesis.

The utility of the title compounds in the preparation of optically active lactones and alcohols is detailed.     

Synthesis and polymerization of optically active L-[α-(N-p-acryloxybenzoyl)alanine ethyl esters]

New optically active monomers L -[α-(N-p-acryloxybenzoyl)alanine ethyl esters] (I) and their polymers were synthesized. The title monomers (I) were prepared by the reaction of 1-p-acryloxybenzoyloxy-4-chlorobenzotriazoles (II) with L -alanine ethyl ester hydrochloride, by aminolysis of the active monoester. The new typical active ester (II) was synthesized by the N-hydroxy compound active-ester methods in excellent yield. Before the synthesis of the optically active monomers was carried out, a model study of the aminolysis of the two active esters was performed.     

Synthesis of optically active α-benzyl paraconic acids and their esters and assignment of their absolute configuration

The cis- and trans-4-benzylparaconic acids and their ethyl esters were synthesized with high enantiomeric excess by hydrolysis of the corresponding diastereomeric lactonic esters using α-chymotrypsin. Thus, at low conversion values, cis- and trans-4-benzyl-5-oxo-3-tetrahydrofurancarboxylic acids were separately isolated with 99% ee and 92% ee, respectively. Both ethyl ester diastereomers were also obtained in enantiopure form. The absolute configuration of the trans-lactonic acid was assigned by ¹H NMR analysis of its ester derivatives with both enantiomers of 1-(9-anthryl)-2,2,2-trifluoroethanol, while that of the cis-lactonic acid was assigned by means of X-ray analysis of a crystalline derivative. The circular dichroism curves of the products obtained are also reported.     

A simplified synthesis of (R)-(−)-muscone using a ring-opening reaction of (R)-(+)-β-methyl-β-propiolactone

A chiral macrocyclic precursor can be constructed via a ring-opening reaction of (R)-(+)-β-methyl-β-propiolactone with a functionalized organocuprate with no loss of enantiomeric excess. The carboxylic acid precursor was used as a chiral building block for the synthesis of chiral muscone and musky macrolactones.     

Synthesis of optically active dihydrocarveol via a stepwise or one-pot enzymatic reduction of (R)- and (S)-carvone

A recombinant enoate reductase LacER from Lactobacillus casei catalyzed the reduction of (R)-carvone and (S)-carvone to give (2R,5R)-dihydrocarvone and (2R,5S)-dihydrocarvone with 99% and 86% de, respectively, which were further reduced to dihydrocarveols by a carbonyl reductase from Sporobolomyces salmonicolor SSCR or Candida magnolia CMCR. For (R)-carvone, (1S,2R,5R)-dihydrocarveol was produced as the sole product with >99% conversion, while (1S,2R,5S)-dihydrocarveol was obtained as the major product, but with a lower de when (S)-carvone was used as the substrate. The one-pot reduction was performed at a 0.1 M substrate concentration, indicating that it might provide an effective synthetic route to this type of chiral compound.