光学纯(S)-2-(苄氧酰氨基)-4-氧代丁酸苄酯的合成和结构表征

以L-蛋氨酸为起始原料,经甲基化、水解、羧基和氨基保护及氯铬酸吡啶嗡盐(PCC)氧化等6步反应,合成了高光学纯度的(S)-2-(苄氧酰氨基)-4-氧代丁酸苄酯。通过1HNMR、IR、MS和mp测试技术表征了其结构;分别用手性柱HPLC和旋光仪法测定了它的化学纯度和光学纯度(ee%值)分别为99.3%和99.5%,产物的总收率为30.0%。     

手性催化剂(4R)-苄氧基-(S)-脯氨酸的合成及其对不对称羟醛反应的催化活性

手性催化剂(4R)-苄氧基-(S)-脯氨酸的合成及其对不对称羟醛反应的催化活性;羟醛反应     

(3S,6S)-及(3S,6R)-3-苄氧甲基-6-甲基-吗啉-2,5-二酮的 制备及其晶体结构

以2-溴丙酸和N-叔丁氧羰基-O-苄基-L-丝氨酸为起始试剂首先制得N-(2-溴丙基)-O-苄基-L-丝氨酸(BPBS), 在N,N-二甲基甲酰胺(DMF)/三乙胺(Et3N)溶剂中80 ℃经9 h后BPBS发生分子内环化反应生成(3S,6S)-3-苄氧甲基-6-甲 基-吗啉-2,5-二酮[(3S,6S)-BMMD]及(3S,6R)-BMMD共存体, 产率70%. 将所制得的共存体以乙酸乙酯为重结晶溶剂, 采用微分重结晶法, 经4次“溶解-部分重结晶”操作循环制得两种纯光学构型的(3S,6S)-BMMD和(3S,6R)-BMMD. 将两种光学纯双手性中心的BMMD分别溶于乙酸乙酯, 室温下培养得(3S,6S)-BMMD和(3S,6R)-BMMD的单晶体, 以X射线衍射法测定上述两种BMMD的分子结构.     

(1R,3S,4S)-2-苄氧羰基-2-氮杂双环[2.2.1]庚烷-3-羧酸的合成

以(R)-(+)-α-甲基苄胺为原料,依次经缩合,Diels-Alder反应,还原,Cbz-保护和水解反应,合成了抗丙肝新药HCV NS3/4A蛋白酶拟肽类抑制剂的重要中间体——(1R,3S,4S)-2-苄氧羰基-2-氮杂双环[2.2.1]庚烷-3-羧酸,总收率66%,其结构经1H NMR和ESI-MS确证。     

(+)-(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。     

(S)-美托洛尔的不对称合成

用自制的(S,S)-Salen Co(Ⅲ)OAc催化剂水解动力学拆分外消旋环氧氯丙烷得到高光学纯的(S)-3-氯-1,2-丙二醇和较高光学纯的(R)-环氧氯丙烷。 以(S)-3氯-1,2-丙二醇为手性原料和4-(2-甲氧基乙基)苯酚缩合,再与氯化亚砜反应得环状亚硫酸酯,最后和异丙胺反应得(S)-美托洛尔,光学纯度大于99%。 另外以(R)-环氧氯丙烷为手性原料和4-(2-甲氧基乙基)苯酚反应,再与异丙胺作用得到(S)-美托洛尔,光学纯度大于92%。 (S)-美托洛尔的总收率为53.9%,结构经IR、1H NMR、13C NMR和MS测试技术确证。 该路线原料利用率高,拆分后的2种产物均能用于目标化合物的合成。     

(2R,4S)-4-甲基-2-哌啶甲酸乙酯的合成

以S-(-)-α-苯乙胺为原料,经一锅法制得1-(1-苄基)-6-乙氧羰基-4-甲基-3,4-二氢哌啶(3),收率58.7%。以10%Pd/C为催化剂,3经催化氢化脱苄合成了4-甲基-2-哌啶甲酸乙酯(4),收率96%;4通过减压分馏得(2R,4S)-4,含量95%,其结构经1H NMR,IR和MS确证。     

(3S,4S)-4-氨基-3-羟基-6-甲基庚酸的合成

价廉易得的L-亮氨酸先以苄基同时保护氨基及羧基得(S)-2-(二苄胺基)-4-甲基戊酸苄酯,进而在碱性条件下与乙腈发生亲核取代反应得(S)-4-(二苄胺基)-6-甲基-3-氧代庚腈,再经硼氢化钠选择性还原羰基得(3S,4S)-4-(二苄胺基)-3-羟基-6-甲基庚腈,用双氧水氧化得(3S,4S)-4-(二苄胺基)-3-羟基-6-甲基庚酸,最后在Pd(OH)2/C-H2作用下脱掉苄基得到(3S,4S)-4-氨基-3-羟基-6-甲基庚酸,即(3S,4S)-statine。整个合成路线总产率为33.6%。     

(R)-/(S)-2-(5-氟尿嘧啶-1-基-乙酰基)氨基-3-羟基丙酸甲酯和DNA相互作用的电化学研究

以自组装制得的DNA修饰电极为工作电极,采用循环伏安法以Fe(CN)63-/4-为电活性指示剂,研究了抗癌药物R型和S型的2-(5-氟尿嘧啶-1-基-乙酰基)氨基-3-羟基丙酸甲酯(简称为(R)-5FUSer和(S)-5FUSer)与DNA的相互作用.循环伏安测试结果表明:(1)体系的式电位随(R)-5FUSer和(S...     

基于同一天然手性源(4R)-羟基脯氨酸的(2S,4S)/(2S,4R)-4-氟谷氨酸的立体专一性合成

基于同一天然手性源(4R)-羟基脯氨酸,通过Mitsunobo反应、全氟丁基磺酰氟作用下的氟化反应以及NaIO4/RuO2作用下的氧化反应,立体专一性地合成了(2S,4S)/(2S,4R)-4-氟谷氨酸.     

Syntheses,Characterization and Stereochemistry of S - and R,S -Hydrogenmalato Dioxotungsten(VI)

Cis -dioxo hydrogenmalato tungstates(VI) j -Na 2 [WO 2 ( S -Hmal) 2 ]·4H 2 O 1 , and Na 2 [WO 2 ( R , S -Hmal) 2 ] 2 (H 3 mal = malic acid) have been prepared from the reactions of excess S- malic acid and R , S -malic acid respectively, with sodium tungstate at ambient temperature. Both complexes were characterized by elemental analyses, conductivity measurement, optical rotation, UV-Vis, IR and NMR spectroscopy. Complex 1 was obtained with predetermined helical chirality at the metal center for a j - cis -configuration, which is established by single crystal X-ray diffraction. The crystal is orthorhombic, space group P 2 1 2 1 2 1 , with unit cell parameters: a = 7.9545(6), b = 10.7440(8), c = 21.045(2)Å, V = 1798.6(2)Å 3 , Z = 4, D c = 2.215 g cm m 3 , F (000) = 1152, R = 0.031, R w = 0.034. Single crystal X-ray diffraction reveals that the cis- dioxo tungstate 1 is octahedrally coordinated by the S -malate through the deprotonated f -hydroxy and f -carboxylate groups, while the g -carboxylic acid groups remain uncomplexed.     

Effective, high-yielding, and stereospecific total synthesis of D-erythro-(2R,3S)-sphingosine from D-ribo-(2S,3S,4R)-phytosphingosine

The synthesis of naturally occurring D-erythro-(2R,3S,4E)-sphingosine from commercially available D-ribo-(2S,3S,4R)-phytosphingosine is described. The key step in the reaction sequence comprises TMSI/DBN promoted regio- and stereoselective oxirane opening of intermediate 2-phenyl-4-(S)-[(1S,2S)-1,2-epoxyhexadecyl]-1,3-oxazoline followed by the in situ trans-elimination of 2-phenyl-4-(S)-[(1S,2R)-1,2-dideoxy-2-iodo-1-trimethylsilyloxyhexadecyl]-1,3-oxazoline.     

Total regioselective and diastereospecific iodolysis of 2,3-epoxyamides promoted by SmI2: synthesis of (2R*,3R*)- or (2R,3S)-2-hydroxy-3-iodoamides

The use of samarium diiodide as a source of iodides is reported. Thus, 2-hydroxy-3-iodoamides were obtained, with total regioselectivity, by treatment of 2,3-epoxyamides, in which the oxirane ring is 2,3-disubstituted or 2,2,3-trisubstituted, with SmI2. The ring-opening reaction was diastereospecific and (2R*,3R*)- or (2R*,3S*)-2-hydroxy-3-iodoamides were obtained from cis- or trans-epoxyamides, respectively. The relative configuration of 2-hydroxy-3-iodoamides was established by X-ray analysis. A mechanism to explain this transformation has been proposed. The starting compounds 1 are easily prepared by the reaction of enolates derived from 2-chloroamides with aldehydes at -78 degrees C.     

Revision of absolute configuration of enantiomeric (methylenecyclopropyl)carbinols obtained from (R)-(-)- and (S)-(+)-epichlorohydrin and methylenetriphenylphosphorane. Implications for reaction mechanism and improved synthesis of antiviral methylenecyclopropane analogues of nucleosides

Absolute configurations of enantiomeric methylenecyclopropanecarbinols obtained by reaction of (R)- and (S)-epichlorohydrin 5 with methylenetriphenylphosphorane or resolution of the corresponding oxaphospholane 6 via a salt with L-(+)-tartaric acid and subsequent Wittig transformation with formaldehyde were revised. The (-)-oxaphospholane 6 has the S,S and (-)-(methylenecyclopropyl)carbinol (4) the R configuration. The configurations of (+)-6 and (+)-4 are then R,R and S, respectively. These assignments are in accord with an initial attack of phosphorane at the oxirane ring of epichlorohydrin. An improved preparation of key enantiomeric intermediates (R)-1a and (S)-1a, important for synthesis of antiviral purine methylenecyclopropane analogues of nucleosides, is also described.     

A practical procedure for the synthesis of esonarimod, (R,S)-2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid,an antirheumatic agent (part 1)

An efficient and practical procedure for the synthesis of esonarimod, (R,S)-2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (1), a new antirheumatic drug, has been developed. The intermediate, 2-methylene-4-(4-methylphenyl)-4-oxobutanoic acid (2), was prepared by Friedel-Crafts acylation of toluene with itaconic anhydride (3) in the presence of aluminum trichloride and nitrobenzene in 63% yield without silica gel column purification. Compound 1 was prepared by Michael addition of 2 with thioacetic acid (4) in 74% yield. Overall, 1 was obtained in 47% yield from 3. The structures and synthetic mechanisms of by-products (five compounds) of 2 were also clarified.     

Determination of (S)-(-)-cathinone and its metabolites (R,S)-(-)-norephedrine and (R,R)-(-)-norpseudoephedrine in urine by high-performance liquid chromatography with photodiode-array detection.

A high-performance liquid chromatographic (HPLC) procedure with photodiode-array detection (DAD) is described for the determination of (S)-(-)-cathinone (S-CA) and its metabolites (R,S)-(-)-norephedrine (R-NE) and (R,R)-(-)-norpseudoephedrine (R-NPE) in urine. Extraction and clean-up of 1-ml urine samples were performed on a cyano-bonded solid-phase column using (+/-)-amphetamine as internal standard. The concentrated extracts were separated on a 3-microns ODS-1 column with acetonitrile-water-phosphoric acid-hexylamine as the mobile phase. Peak detection was done at 192 nm. The detection limits for S-CA and R-NE/R-NPE in urine were 50 and 25 ng/ml, respectively. The differentiation of the enantiomers of cathinone and norephedrine was achieved by derivatization with (S)-(-)-1-phenylethyl isocyanate to the corresponding diastereomers followed by HPLC-DAD on a 5-microns normal-phase column. The R and S enantiomers of norpseudoephedrine were determined by gas chromatography-mass spectrometry after on-column derivatization with (S)-(-)-N-trifluoroacetylprolyl chloride. Following a single oral dose of 0.5 mg/kg of S-CA, the concentrations found in urine ranged from 0.2 to 3.8 micrograms/ml of S-CA, from 7.2 to 46.0 micrograms/ml of R-NE and from 0.5 to 2.5 micrograms/ml of R-NPE.     

A Convenient Approach to the Enantiopure (1S,2S,4S,5S)-and (1R,2S,4R,5S)-2,5-Bis(phenylmethyl)-1,4-diazabicyclo[2.2.2]-octane

Introduction1,4 Diazabicyclo[2 .2 .2 ]octane (DABCO)wasre portedtocatalyzeorganicreactionsduetoitsstrongbasici ty .1,2 Severalchiraltrans 2 ,3 disubstitutedDABCOshavebeensynthesizedandappliedtotheasymmetricBaylis Hillmanreaction3andvicinalhydroxylation .4ThefirstsynthesisofthetitlecompoundwasreportedbySoai5from (2S ,5S) bis(phenylmethyl)piperazine (1) ,asshowninScheme 1.Butthisprocedureislengthy ,andtheoverallyieldisnotsosatisfactory .Besides ,thereport edmethodforthepreparationof 1is…     

Total synthesis of (-)-(6S,7S,8S,9R,10S,2'S)-membrenone-A and (-)-(6S,7S,8S,9R,10S)- membrenone-B and structural assignment of membrenone-C

[reaction: see text] (-)-(6S,7S,8S,9R,10S,2'S)-Membrenone-A and (-)-(6S,7S,8S,9R,10S)-membrenone-B were prepared in 11 steps (3% and 2.4% overall yield, respectively). Key steps included a tin(II)-mediated aldol followed by a syn selective reduction, giving the C7-C9 stereocenters, a second chain extending aldol coupling, and a p-TsOH-promoted cyclization/dehydration giving the common gamma-dihydropyrone precursor. We have thus established that synthetic (-)-(6S,7S,8S,9R,10S,2'S)-membrenone-A, (-)-(6S,7S,8S,9R,10S)-membrenone-B, and (-)-(6S,7S,8S,9R,10S)-membrenone-C are the enantiomers of the natural products.     

(S)-2-[(R)-fluoro(phenyl)methyl]oxirane: a general reagent for determining the ee of alpha-chiral amines

(S)-2-[(R)-Fluoro(phenyl)methyl]oxirane is a new, synthetic, yet enantiopure, chiral resolution reagent, readily obtained from enantiopure (2S,3S)-phenylglycidol, that reacts with a variety of alpha-chiral primary and secondary amines in a straightforward manner through a regioselective ring-opening. Diastereomeric products are easily identified and quantified by (19)F, (1)H, and (13)C NMR and by HPLC, which makes this fluorinated compound a most versatile reagent for the analysis of scalemic mixtures of amines. [reaction: see text]