The Stereoselective Synthesis of 2‐Aryl‐2‐hydroxybutanoic Acid via Menthyl Chiral Auxiliaries

In the presence of titanium(IV) tetraethoxide ((EtO)₄Ti), menthyl arylglyoxylates are prepared by transesterification of ethyl arylglyoxylates and natural (−)‐(1R,2S,5R)‐menthol. Using menthyl as a chiral auxiliary, the corresponding novel (R)‐menthyl 2‐aryl‐2‐hydroxybutanoates are synthesized by the addition of Et₂Zn with menthyl arylglyoxylates. The structures of the products are characterized by IR and ¹H‐ and ¹³C‐NMR spectroscopy, mass spectrometry, and elemental analysis. The diastereoselectivities are analyzed by HPLC. The addition reactions are completed with good yields and high diastereoisomeric excess (de up to 95%), and, after hydrolysis, the (R)‐2‐aryl‐2‐hydroxybutanoic acids are obtained with high optical purities.     

Chirality Control by Substituents in the Asymmetric Addition of Et_2Zn to Aromatic Aldehydes Catalyzed by cis-(1 R,2S)-2- Benzamidocyclohexanecarboxylic Acid Derived 1,3-Aminoalcohols

A series of novel optically active 1,3‐aminoalcohols based on cis‐(1R,2S)‐2‐benzamidocyclohexanecarboxylic acid and trans‐(1R,2R)‐2‐benzamidocyclohexanecarboxylic acid were synthesized and used in the asymmetric diethylzinc addition to aromatic aldehydes. Not only the enantioselectivity but also the stereochemistry of the product were controlled by the N‐substituents and the substituents on the vicinity carbon to hydroxyl group of the cis‐derivatives.     

Novel antitumor dinuclear platinum (II) complexes with a new chiral tetradentate ligand as the carrier group

Seven dinuclear platinum(II) complexes with a novel chiral tetradentate ligand, (1R,1′R,2R,2′R)‐N¹,N^1′‐(1,4‐phenylenebis(methylene))dicyclohexane‐1,2‐diamine, were designed, synthesized and spectrally characterized. All the complexes were evaluated for their in vitro cytotoxicity against human HepG‐2, A549, HCT‐116 and MCF‐7 cancer cell lines. The results indicated that all compounds showed positive biological activity against HepG‐2, A549 and HCT‐116 cancer cell lines. In particular, compounds D7 and D2 showed better activity than carboplatin against HepG‐2 and A549 and compound D7 also showed an activity close to that of oxaliplatin. Copyright © 2015 John Wiley & Sons, Ltd.     

Asymmetric Henry reactions of aldehydes with various nitroalkanes catalyzed by copper(II) complexes of novel chiral N‐monoalkyl cyclohexane‐1,2‐diamines

A number of novel chiral diamines 3 , (1R,2R)‐N‐monoalkylcyclohexane‐1,2‐diamines, were designed and synthesized from trans‐cyclohexane‐1,2‐diamine and applied to the catalytic asymmetric Henry reaction of benzaldehyde and nitromethane to provide β‐nitroalcohol in high yield (up to 99%) and good enantiomeric excess (up to 89%). By using ligand (1R,2R)‐N¹‐(4‐methylpentan‐2‐yl)cyclohexane‐1,2‐diamine ( 3g ), the reaction was optimized in terms of the metal ion, temperature, solvent and base. Further experiments indicated that the complex, 3g –Cu(OAc)₂, was an efficient catalyst in the asymmetric Henry reaction between different aldehydes and nitromethane, and the desired products have been obtained with high chemical yields (up to 99%) and high enantiomeric excess (up to 93%). The optimized catalyst promoted the diastereoselective Henry reaction of various aldehyde substrates and nitroalkane, which gave the corresponding anti‐selective adduct with up to 99% yield and 83:17 anti/syn selectivity. Upon scaling up to gram quantities, the β‐nitroalcohol was obtained in good yield (96%) with excellent selectivities (93% ee). The chiral induction mechanism was tentatively explained on the basis of a previously proposed transition‐state model. Copyright © 2014 John Wiley & Sons, Ltd.     

The First Stereoselective Total Synthesis of Naturally Occurring,Bioactive (3R,5R)‐1‐(4‐Hydroxyphenyl)‐7‐phenylheptane‐3,5‐diol and the Synthesis of Its Enantiomer

The first stereoselective total synthesis of the naturally occurring anti‐emetic diarylheptanoid (3R,5R)‐1‐(4‐hydroxyphenyl)‐7‐phenylheptane‐3,5‐diol ( 1 ) was accomplished starting from 4‐hydroxybenzaldehyde and involving a Sharpless kinetic resolution and an asymmetric epoxidation as the key steps (Scheme 2). The enantiomer 1a of this compound was also simultaneously prepared.     

Asymmetric Mannich‐Type Synthesis of N‐Phosphinyl α‐Aminophosphonic Acid Monoesters

A convenient diastereoselective synthesis of diisopropyl (2R,3R)‐3‐{{{(R/S)‐aryl[(diethoxyphosphinyl)amino]methyl}hydroxyphosphinyl}oxy}‐2‐hydroxybutanedioate through Mannich‐type reactions is reported. The reactions take place under mild conditions in good yields, and this makes it possible to introduce various substituents at the α‐position to the P‐atom of α‐aminophosphonates. The chiral diisopropyl (4R,5R)‐2‐chloro‐1,3,2‐dioxaphospholane‐4,5‐dicarboxylate ( 3 ) was found to be a good phosphonylating agent in this stereoselective reaction.     

Efficient Synthesis of a Styryl Analogue of (2S,3R,4E)‐N2‐Octadecanoyl‐4‐tetradecasphingenine via Cross‐Metathesis Reaction

The first total synthesis of sphingolipid (2S,3R,4E)‐N²‐octadecanoyl‐4‐tetradecasphingenine ( 1a ), a natural sphingolipid isolated from Bombycis Corpus 101A, and of its styryl analogue 1b was achieved in good overall yield (Schemes 1 and 2). The key step involved the installation with (E) stereoselectivity of a long lipophilic chain or phenyl group on allyl alcohol derivative 3 via a cross‐metathesis reaction (→ 5a or 5b ). The N‐Boc protected 3 was easily accessible from (S)‐Garner aldehyde.     

Enantiospecific Synthesis of (R)‐3‐Amino‐4‐(2,4,5‐trifluorophenyl)butanoic Acid Using (S)‐Serine as a Chiral Pool

Starting from (S)‐serine, a new method was developed for the synthesis of the β‐amino acid part of sitagliptin in ten steps and with an overall yield of 30%. The crucial step of the synthesis was the ring opening of N‐ and O‐protected (R)‐aziridin‐2‐methanol with (2,4,5‐trifluorophenyl)magnesium bromide to give N‐ and O‐protected (R)‐2‐amino‐3‐(2,4,5‐trifluorophenyl)propan‐1‐ol.     

Enantioselective Synthesis of (−)‐(R)‐Cordiachromene and (−)‐(R)‐Dictyochromenol Utilizing Intramolecular SNAr Reaction

A simple and efficient enantioselective synthesis of chromene, (?)‐(R)‐cordiachromene ( 1 ), and (?)‐(R)‐dictyochromenol ( 2 ) has been accomplished. This convergent synthesis utilizes intramolecular S_NAr reaction for the formation of chroman ring, and Seebach's method of ‘self‐reproduction of chirality’ should establish the (R)‐configuration of the C(2) side chain as key steps.     

An Efficient Stereoselective Total Synthesis of Bioactive (3R,5R)‐1‐(4‐Hydroxyphenyl)‐7‐phenylheptane‐3,5‐diol via Asymmetric Aldol Reaction

An efficient stereoselective total synthesis of (3R,5R)‐1‐(4‐hydroxyphenyl)‐7‐phenylheptane‐3,5‐diol ( 1 ) is reported based on the Mukaiyama aldol reaction. The total synthesis of compound 1 was accomplished with 30% overall yield in simple eight steps from commercially available trans‐cinnamaldehyde.     

Asymmetric hydration of alkenes catalyzed by wool‐palladium complex

A wool‐palladium complex has been found to be able to catalyze the asymmetric hydration of 1‐octene to (S)‐(+)‐2‐octanol and 1‐decene to (R)‐(+)‐2‐decanol under 1 atm N₂ and at 70°C. The optical yields were greatly affected by Pd content in wool‐palladium complex, reaction time and so on, when the proper conditions were selected, (S)‐(+)‐2‐octanol and (R)‐(+)‐2‐decanol could be obtained in 83.2 and 75.6%e.e. optical yield respectively. This chiral natural biopolymer‐palladium complex catalyst was very easy to prepare and could be reused several times without appreciable change in catalytic activity. Copyright © 2004 John Wiley & Sons, Ltd.     

A New Cembranoid Diterpene and Other Related Metabolites from the South‐China‐Sea Soft Coral Lobophytum crassum

A new hydroperoxy‐substituted cembranoid diterpene, 2‐hydroperoxysarcophine (= (1aR*,4E,11E,14aR*)‐2,3,6,7,10a,13,14,14a‐octahydro‐10a‐hydroperoxy‐1a,5,8,12‐tetramethyloxireno[9,10]cyclotetradeca[1,2‐b]furan‐9(1aH)‐one; 1 ), was isolated from the marine soft coral Lobophytum crassum. Also isolated were two other cembranoid diterpenes, obtained for the first time from a natural source, i.e., 7β,8β‐epoxy‐4α‐hydroxycembra‐1(15),2,11‐trien‐16,2‐olide ( 2 ) and 7β,8β‐epoxy‐4β‐hydroxycembra‐1(15),2,11‐trien‐16,2‐olide ( 3 ), along with three further cembranoid derivatives, five sterols, and two open‐chain metabolites. Their structures and relative configurations were elucidated on the basis of extensive spectroscopic analyses including 1D‐ and 2D‐NMR, and HR‐ESI‐MS experiments.     

High‐performance liquid chromatographic enantioseparation of isoxazoline‐fused 2‐aminocyclopentanecarboxylic acids on a chiral ligand‐exchange stationary phase

The application of a chiral ligand‐exchange column for the direct high‐performance liquid chromatographic enantioseparation of unusual β‐amino acids with a sodium N‐((R)‐2‐hydroxy‐1‐phenylethyl)‐N‐undecylaminoacetate‐Cu(II) complex as chiral selector is reported. The investigated amino acids were isoxazoline‐fused 2‐aminocyclopentanecarboxylic acid analogs. The chromatographic conditions were varied to achieve optimal separation. The effects of temperature were studied at constant mobile phase compositions in the temperature range 5–45°C, and thermodynamic parameters were calculated from plots of lnk or lnα versus 1/T. Δ(ΔH°) ranged from –2.3 to 2.2 kJ/mol, Δ(ΔS°) from –3.0 to 7.8 J mol^?1 K^?1 and –Δ(ΔG°) from 0.1 to 1.7 kJ/mol, and both enthalpy‐ and entropy‐controlled enantioseparations were observed. The latter was advantageous with regard to the shorter retention and greater selectivity at high temperature. Some mechanistic aspects of the chiral recognition process are discussed with respect to the structures of the analytes. The sequence of elution of the enantiomers was determined in all cases.     

Practical Synthesis of (S)‐(+)‐3‐Octanol by Lipase‐Catalyzed Enantioselective Acetylation

(S)‐(+)‐3‐Octanol (S)‐1 was prepared in high enantiomeric excess through catalyzed acetylation of racemic alcohol 1 by using lipase from Candida antarctica (Chirazyme L‐2) in the presence of vinyl acetate in toluene at 30°C. The pure (S)‐1 was obtained in 73% isolated yield with 62% conversion. Moreover, acetate (R)‐2 was converted to (S)‐1 via mesylation and followed by hydrolysis using sodium bicarbonate solution in 44% yield.     

Quantum chemical studies of peptide nucleic acid monomers and role of cyclohexyl modification on backbone flexibility

Peptide nucleic acids (PNA) bind sequence specifically to DNA/RNA and are of major interest for all fields of molecular biology and could form the basis for gene‐targeted drugs. Modifications are introduced in PNA to overcome problems associated with orientational selectivity in binding, to restrict conformational flexibility of backbone, and to discriminate binding for either DNA or RNA. The addition of geometrical isomers (1R,2S and 1S,2R) of cyclohexyl ring in the backbone of PNA could bring rigidification to PNA backbone and may impart specificity toward RNA. Therefore, quantum chemical studies are aimed to explore the conformational space, to find out preferred stable conformations of PNA and modified (1R,2S and 1S,2R) cyclohexyl PNA monomer. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009     

双功能手性联萘酚配体在炔基锌对醛的不对称加成反应选择性能研究

单体2-溴吡啶, 2-溴-5-甲基吡啶, 2-氯-4-氟吡啶, 2-氯-3-三氟甲基吡啶分别与( R )-3,3′-二硼酸-2,2′-二甲氧基-1,1′-联萘 [( R )-2]在钯催化下, 通过Suzuki交叉耦合反应合成得到四个类似手性化合物( R )-3a-d。将它们应用到炔基锌对醛的不对称催化加成反应中,结果表明( R )-3a和( R )-3b的催化效果不好, 而( R )-3d只对脂肪醛有很好的催化效果,( R )-3c则对这类不对称催化反应均有很好的催化效果, 能给出高达95%的收率和99%的选择性结果。结果还表明所产生相应炔丙醇异构体构型为S,这与手性催化剂构型相反。     

New Bisabolane Sesquiterpenes from the Rhizomes of Curcuma xanthorrhiza Roxb. and Their Inhibitory Effects on UVB‐Induced MMP‐1 Expression in Human Keratinocytes

Two new bisabolane sesquiterpenoids, 1 and 2 , along with five known ones, 13‐hydroxyxanthorrhizol ( 3 ), 12,13‐epoxyxanthorrhizol ( 4 ), xanthorrhizol ( 5 ), β‐curcumene ( 6 ), and β‐bisabolol ( 7 ), were isolated from the rhizomes of Curcuma xanthorrhiza Roxb . The chemical structures of the new compounds were determined to be (7R,10R)‐10,11‐dihydro‐10,11‐dihydroxyxanthorrhizol 3‐O‐β‐D ‐glucopyranoside ( 1 ) and (?)‐curcuhydroquinone 2,5‐di‐O‐β‐D ‐glucopyranoside ( 2 ) on the basis of 1D‐ and 2D‐NMR spectroscopic analyses and optical‐rotation characteristics. Compounds 2 and 3 decreased MMP‐1 expression in UVB‐treated human keratinocytes by ca. 8.9‐ and 7.6‐fold at the mRNA level, and by ca. 9.2‐ and 6.6‐fold at the protein level, respectively. The results indicate that the isolated compounds may have anti‐aging effects through inhibition of MMP‐1 expression in skin cells.     

Stereo‐Inversion in the (4R)‐γ‐Decanolactone Synthesis by Saccharomyces cerevisiae: (2E,4S)‐4‐Hydroxydec‐2‐enoic Acid Acts as a Key Intermediate

Methyl (2E,4R)‐4‐hydroxydec‐2‐enoate, methyl (2E,4S)‐4‐hydroxydec‐2‐enoate, and ethyl (±)‐(2E)‐4‐hydroxy[4‐²H]dec‐2‐enoate were chemically synthesized and incubated in the yeast Saccharomyces cerevisiae. Initial C‐chain elongation of these substrates to C₁₂ and, to a lesser extent, C₁₄ fatty acids was observed, followed by γ‐decanolactone formation. Metabolic conversion of methyl (2E,4R)‐4‐hydroxydec‐2‐enoate and methyl (2E,4S)‐4‐hydroxydec‐2‐enoate both led to (4R)‐γ‐decanolactone with >99% ee and 80% ee, respectively. Biotransformation of ethyl (±)‐(2E)‐4‐hydroxy(4‐²H)dec‐2‐enoate yielded (4R)‐γ‐[²H]decanolactone with 61% of the ²H label maintained and in 90% ee indicating a stereoinversion pathway. Electron‐impact mass spectrometry analysis (Fig. 4) of 4‐hydroxydecanoic acid indicated a partial C(4)→C(2) ²H shift. The formation of erythro‐3,4‐dihydroxydecanoic acid and erythro‐3‐hydroxy‐γ‐decanolactone from methyl (2E,4S)‐4‐hydroxydec‐2‐enoate supports a net inversion to (4R)‐γ‐decanolactone via 4‐oxodecanoic acid. As postulated in a previous work, (2E,4S)‐4‐hydroxydec‐2‐enoic acid was shown to be a key intermediate during (4R)‐γ‐decanolactone formation via degradation of (3S,4S)‐dihydroxy fatty acids and precursors by Saccharomyces cerevisiae.     

Enzymatic Enantioselective Synthesis of （R）－2－Trimethylsilyl－2－hydroxyl－propionitrile by Defatted Apple Seed Meal

IntroductionOverthepastyears ,thesynthesisofchiralaldehyde cyanohydrinswaswellstudied .1Incontrasttochiralalde hyde cyanohydrins ,therewereonlyfewreportsaboutthepreparationofopticallyactiveketone cyanohydrins ,2 whichareusefulstartingmaterialsandintermediatesforthesyn thesisofmanychiralnaturalproducts .3Wethereforefo cusedonthepreparationofopticallyactivesiliconcontain ing (R ) ketone cyanohydrin ((R ) 2 trimethylsilyl 2 hy droxyl propionitrile)usingacetonecyanohydrinastran scyanationagen…     

Reversed‐phase liquid chromatographic determination of enantiomers of atenolol in rat plasma using derivatization with Marfey's reagent

An HPLC method was established for enantioseparation of (R,S)‐atenolol (ATE) and determination of enantiomers in rat plasma. Marfey's reagent (1‐fluoro‐2,4‐dinitrophenyl‐5‐L‐alanine amide, FDNP‐L‐Ala‐NH₂, MR) was used as chiral derivatizing reagent with detection of diastereomers at 340 nm. It was shown that the R‐isomer eluted before the S‐isomer. The method was validated for linearity, repeatability, limits of detection and limit of quantification (LOQ). Recovery of ATE at LOQ was 92.8% for (R)‐ATE and 92.6% for (S)‐ATE. Copyright © 2009 John Wiley & Sons, Ltd.