A practical synthesis of （-）fosfomycin from its enantiomer

（＋）-cis-（1S, 2R）-Epoxypropylphosphonic acid, the enantiomer of fosfomycin, which is the industrial side-product in the preparation of the antibiotic fosfomycin, was converted into （-）fosfomycin by a seven-step procedure. The esterification of the dihydroxyphosphonic intermediate was the key step. The title compound was obtained in good yield and its optical purity was up to the medicine quality standard of Chinese Pharmacopoeia.     

Asymmetric Synthesis of （R）- and （S）-Moprolol

A simple and effective procedure for the enantioselective synthesis of （R）- and （S）-moprolol was described. The key step was the asymmetric synthesis of enantiopure （R）- and （S）-guaifenesin, which were synthesized from enantioenriched （R）-3-chloro-l,2-propanediol and （S）-epichlorohydrin via kinetics of hydrolysis resolution of racemic epichlorohydrin by chiral Salen-Co^Ⅲ complex. The e.e. values of both the optical compounds were above 98%, and the chemical structures of the target compounds were confirmed by ^1H NMR, ^13C NMR, IR, and MS.     

Convenient synthesis of （2S,3R,4R,5S,6R）-2-（3-（4-ethylbenzyl）-4- chlorophenyl）-6-（hydroxymethyl）-tetrahydro- 2H-pyran-3,4,5-triol

A convenient approach for the preparation of （2S,3R,4R,5S,6R）-2-（3-（4-ethylbenzyl）-4-chlorophenyl）-6-（hydroxymethyl）- tetrahydro-2H-pyran-3,4,5-triol I is developed. The target compound via four steps is synthesized from 4-bromo-2-（bromomethyl）- 1-chlorobenzene and the isomers of undesired ortho-products were avoided during the preparation.     

Synthesis,Bioactivity and Crystal Structure Analysis of 2-（Benzo [d]isothiazol-3-yloxy）-N-（3-cyano-l-（4- fluorophenyl）-lH-pyrazol-5-yl） Acetamide

A novel benzisothiazolin-3-one derivative, 2-（benzo[d]isothiazol-3-yloxy）-N-（3- cyano-l-（4-fluorophenyl）-lH-pyrazol-5-yl） acetamide （8）, was synthesized from the initial compound benzo[d]isothiazol-3（2H）-one （BIT） 1 and 4-fluoroaniline 3. The structure of the target compound 8 was determined by elemental analyses, IR and 1H NMR. The single crystals of intermediate compound 6 and the target compound 8 were obtained and determined by X-ray diffraction analysis. The preliminary biological activity was also evaluated and the results showed tile target compound exhibited a good anti-microbial activity.     

Two pairs of unusual scalemic enantiomers from Isatis indigotica leaves

Two pairs of unusual scalemic enantiomers with a novel carbon skeleton of 2-[1'-('-hydroxy-3',5'-dimethoxyphenyl)ethyl]-2-methoxyindolin-3-one, named isatidifoliumindolinones A–D(1–4), were isolated from an aqueous extract of Isatis indigotica leaves(da qing ye). Their structures including absolute configurations were determined by spectroscopic data analysis combined with comparison of their experimental CD and calculated ECD spectra. Validity of the ECD spectra calculation to assign the absolute configurations is discussed. Plausible biosynthetic pathways of 1–4 are proposed.Stereochemistry-dependent activity against LPS-induced NO production in BV2 cells was observed,and among the stereoisomers compound 4 is most active.     

Lipase－Catalyzed Resolutions of both Enantiomers of Ornidazole and Secnidazole

The resolutions of both enantiomers of the ornidazole and sec-nidazole were achieved with high enantiomeric excesses (ee>99%) by acylation of the corresponding racemates with vinylac-etate in the presence of lipase Amano AK (from Pseudomonassp.). The assignments of the absolute configurations of (+) or(-)-ornidazole and secnidazole are described.     

Structure and Biological Activities of 2-（ 1,3-Dithiolan-2-ylidene）-1-phenyl-2- （ 1,2,4-triazol-1 -yl ） ethanone

In order to find leading compounds with an excellent fungicidal activity, the title compound 2-（ 1,3-dithiolan-2- yl-idene）-1-phenyl-2-（ 1,2,4-tfiazol-1-yl） ethanone was synthesized according to the biological isosterism and its structure was confirmed by means of IR, MS, ^1 H NMR and elemental analysis. The single crystal structure of the title compound was determined by X-ray diffraction. The preliminary biological test shows that the synthesized compound exhibits some biological activities.     

First total synthesis of 10α-hydroxy-4-muurolen-3-one and its C10-isomer

An efficient synthetic route to muurolane type sesquiterpenes starting from （R）-carvone, employing allylic diazene rearrangement and the ring closing methesis （RCM） reaction as key steps, is described. The first asymmetric total synthesis of （-）-10α- hydroxy-4-muurolen-3-one 11 and （-）-10β-hydroxy-4-muurolen-3-one C was accomplished. Through the total synthesis, the absolute configurations of the natural products A, B and C were established.     

Enantioselective Total Synthesis of the （＋） Antipode of Zeylenone

Starting from shikimic acid, the total synthesis of zeylenone was studied. The product was proved to be the ( )antipode of zeylenone through analysis and comparison of their respective spectra (including NMR, MS, IR and CD) and optical data. The absolute configuration of the natural product was thus determined to be (1 S,2S,3R).     

Syntheses and Biological Activities of Novel 3-Bromo-1-（3-chloropy- ridin-2-yl）-N-hydroxy-N-aryl- 1H-pyrazole-5-carboxamides

A series of novel 3-bromo-1-（3-chloropyridin-2-yl）-N-hydroxy-N-aryl-lH-pyrazole-5-carboxamides was synthesized by the reaction of pyrazole carbonyl chloride with each of substituted phenylhydroxyamines. The latter ones were prepared in good yields by reducing substituted nitrobenzene compounds with Zn/NH4CI reductant system in alcohol. Structures of the title compounds were determined by IR, 1H NMR, and HRMS. Their insecticidal and fungicidal activities were evaluated by larvicidal test against oriental armyworm and the mycelium growth rate method, respectively.     

Novel ligands based on bromosubstituted hydroxycarbonyl [2.2]paracyclophane derivatives: synthesis and application in asymmetric catalysis

New planar-chiral hydroxycarbonyl [2.2]paracyclophane derivatives, 4-acetyl-13-bromo-5-hydroxy[2.2]paracyclophane (Br-АНРС, 63%) and 4-benzoyl-13-bromo-5-hydroxy[2.2]paracyclophane (Br-BHPC, 53%), were synthesized and reacted with the enantiomers of α-phenylethylamine to form corresponding Schiff bases, 12-bromo-4-hydroxy-5[1-(1-phenyl-ethylimino)-ethyl]-[2.2]paracyclophane and 12-bromo-4-hydroxy-5[1-(1-phenyl-ethylimino)-(phenyl)methylen-[2.2]paracyclophane. The diastereomers of the imines were resolved and their absolute configurations and consequently the corresponding configurations of the enantiomers of Br-АНРС were determined by X-ray diffraction. Enantiomerically pure Schiff bases were applied as ligands to form catalysts for the enantioselective addition reaction of diethylzinc with benzaldehyde where 1-phenylpropanol was obtained with 77–91% ee.     

Synthesis of the optical isomers of 4-[1-(4-tert-butylphenyl)-2-oxo- pyrrolidine-4-yl]methyloxybenzoic acid (S-2) and their biological evaluation as antilipidemic agent

The enantiomers of (+/-)-4-[1-(4-tert-butylphenyl)-2-oxo-pyrrolidine- 4-yl]methyloxybenzoic acid (S-2), a new antilipidemic agent having dual action on the plasma triglyceride (TG) and cholesterol (Cho) lowering effects, were prepared via separation by Chiralcel OJ column chromatography of their methyl ester and also by the same method as the described racemate's synthesis from optically active 1-(4-tert-butylphenyl)-2-oxo-pyrrolidine-4-carboxylic acid respectively. These optically active carboxylic acids were prepared by the resolution of diastereomeric N-[(S)-(-)-[4-methyl-(alpha-methyl)benzyl]]-1-(4-tert-butylphenyl)-2-oxo - pyrrolidine-4-carboxyamide using silica gel column chromatography, followed by deamination with N2O4. The absolute configurations for the enantiomers of S-2 were indirectly determined using X-ray analysis of the 4-bromo-2-fluorobenzamide of the (+)-4-[1-(4-tert-butylphenyl)-2- oxo-pyrrolidine-4-yl]-methyloxybenzoic acid. S-2 and its enantiomers showed an essentially equipotent activity on the fatty acid- and sterol-biosynthesis inhibition in vitro. On the other hand, in the in vivo activity, (S)-(+)-4-[1-(4-tert-butylphenyl)-2-oxo-pyrrolidine- 4-yl]methyloxybenzoic acid (S-2E) was superior in the lowering abilities of the plasma TG and phospholipid(PL) and was chosen as a candidate for a novel antilipidemic agent. The difference in the in vivo activity among S-2 and its enantiomers was explained from the pharmacokinetics after administration p.o.     

Synthesis and biological activities of optical isomers of 2-(4-chlorophenyl)-5,6-dihydro-(1)benzothiepino[5,4-c]pyridazin-3(2H)-o ne 7-oxide.

Two enantiomers of 2-(4-chlorophenyl)-5,6-dihydro-(1)benzothiepino[5,4- c]pyridazin-3(2H)-one 7-oxide ((+/-)-1: Y-23684) were synthesized in high yields by asymmetric oxidation of the synthetic precursor (2) using modified Sharpless reagent. Among the oxidants tested, cumene hydroperoxide (CHP) gave the highest optical and chemical yields, while tert-butyl, tert-amyl, and 1,1,3,3-tetramethylbutyl hydroperoxides did not show such high enantio-selectivities. The absolute configuration of (+)-1 enantiomer synthesized from 2, Ti(O-iso-Pr)4, (-)-diethyl tartarate, and CHP was determined to be S by X-ray crystallographic analysis. Both enantiomers, S-(+)-1 and R-(-)-1, and (+/-)-1 had approximately equivalent in vivo activities to antibicuculline test in mice and anticonflict test in rats, although S-( + )-1 showed about three times higher affinity to benzodiazepine receptor than R-(-)-1 in [3H]diazepam binding assay.     

Special features of the alkylation of 7-bromo-5-(2-chlorophenyl)- 3-hydroxy-1,2-dihydro-3h-1,4-benzo- diazepin-2-one with alkyl tosylates

On interacting 7-bromo-5-(2-chlorophenyl)-3-hydroxy-1,2-dihydro-3H-1,4-benzodiazepin-2-one with methyl, hexyl, dodecyl, and cetyl tosylates, 1-alkyl-7-bromo-5-(2-chlorophenyl)-1,2,4,5-tetrahydro-3H-1,4-benzodiazepin-2,3-diones, and 1-alkyl-7-bromo-5-(2-chlorophenyl)-3-hydroxy-1,2-dihydro-3H-1,4-benzodiazepin- 2-ones were obtained. Only the dione was formed in the case of hexyl tosylate. On alkylating with methyl tosylate only the 3-hydroxy derivative was formed. It was shown that at pH 14 the 1-cetyl and 1-dodecyl-3-hydroxy derivatives were completely converted into the corresponding diones. The molecular and crystal structures of the compounds were established by X-ray structural analysis.     

Enzyme-catalyzed synthesis and absolute configuration of (1S,2R,5S)- and (1R,2S,5R)-2-(1-hydroxyethyl)-1-(methoxymethyloxyethyl)cyclobutane-1-carbonitrile,key intermediates for the preparation of chiral cyclobutane-containing pheromones

Formal synthesis of chiral grandisol and the oleander scale pheromone and their antipodes can be achieved through a convenient lipase-catalyzed enantiodifferentiation process of the common cyclobutane intermediate (±)-2-(1-hydroxyethyl)-1-(methoxymethyloxyethyl)cyclobutane-1-carbonitrile 3. The resolution afforded both enantiomers in almost enantiomerically pure form and their absolute configurations were assigned on the basis of the Δδ values for their (R)- and (S)-MTPA esters.     

Synthesis of novel 6-(substituted amino)-4-(4-ethoxyphenyl)-1-phenyl-2(1H)-pyridinones via azo coupling

Abstract  

6-(Substituted amino)-4-(4-ethoxyphenyl)-1-phenyl-2(1H)-pyridinones were prepared from β-aryl glutaconic acid, which, on fusion with aniline, results in 4-(4-ethoxyphenyl)-1-phenylpyridine-2,6(1H,5H)-dione. This, on further treatment with phosphorus oxychloride gave 6-chloro-4-(4-ethoxyphenyl)-1-phenyl-2(1H)-pyridinone, and further treatment with secondary amines yielded 6-(substituted amino)-4-(4-ethoxyphenyl)-1-phenyl-2(1H)-pyridinones. These were subjected to azo coupling with different aryldiazonium chlorides furnishing two isomers, which were separated by column chromatography. All compounds were characterized by elemental analysis, and use of IR and NMR spectral data, and were evaluated for antimicrobial activity.     

Enantiomeric separation of novel anticancer agent 5-hydroxy-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-cyclopent-2-en-1-one

The enantiomers of 5-hydroxy-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-cyclopent-2-en-1-one, a novel anticancer agent, were separated by derivatisation with caronaldehyde, separation of the resulting diastereoisomers of the corresponding esters by silica gel column chromatography and regeneration of alcohols (S)-5-hydroxy-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-cyclopent-2-en-1-one and (R)-5-hydroxy-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-cyclopent-2-en-1-one under aqueous conditions. The absolute configuration of the enantiomers was determined by 1H NMR studies of the corresponding Mosher esters. Alternatively, the enantiomers were separated by preparative HPLC to collect the (S)- and (R)-5-hydroxy-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-cyclopent-2-en-1-ones with high purity which was comparable with that obtained by the chemical method. The details of these methods have been presented herein.     

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…     

R 和 s-1-(3'-溴-4'-甲氧基)苄基-2-甲基-6-甲氧基-7-羟基-1, 2,3,4-四氢异喹啉的合成

本文报道了R和S-1-(3'-溴-4'-甲氧基)苄基-2-甲基-6-甲氧基-7-羟基-1,2,3,4-四氢异喹啉的合成。     

Synthesis,resolution, and absolute stereochemistry of (-)-blestriarene C

A naturally occurring 1,1'-biphenanthrene, blestriarene C (1), was prepared in 13 steps and 30% overall yield. The key steps are the ester-mediated nucleophilic aromatic substitution on 2,6-di-tert-butyl-4-methoxyphenyl 5-isopropoxy-2-methoxybenzoate (4) by 2-methoxy-4-methoxymethoxy-6-methylphenylmagnesium bromide (5) and a novel intramolecular cyclization of the resulting 4-isopropoxy-2'-methoxy-4'-methoxymethoxy-6'-methylbiphenyl-2-carboxylic ester 14 to 7-isopropoxy-4-methoxy-2-(methoxymethoxy)phenanthren-9-ol (15). The racemic blestriarene C was optically resolved by chiral HPLC on a preparative scale to give several 10-mg yields of both the enantiomers in up to 95% ee. The absolute stereochemistry was determined to be S(a)-(-) by the axial chirality recognition method, which was based on the stereospecific formation of a 12-membered cyclic diester containing two biaryl-o,o'-diyl unites joined by ester -CO(2)- linkages. The validity of the method was confirmed by an X-ray crystallographic analysis and ab initio conformational analyses of such 12-membered cyclic diesters. It was found that blestriarene C and its 7,7'-diisopropyl ether 2 underwent rapid photoracemization even under ambient light exposure.