New chiral phosphine-phosphonites derived from (2R,3R)-dimethyl tartrate, (S)-binaphthol and (1R,2S)-ephedrine

The reaction of 2-lithiophenyldiphenylphosphine with phosphorus trichloride afforded the new unsymmetric phosphine, dichloro(2-diphenylphosphinophenyl)phosphine (4). Condensation of 4 with (a) (2R,3R)-dimethyl tartrate or (b) (S)-binaphthol in the presence of triethylamine gave new chiral phosphine-phosphonite ligands, (2R,3R)-[2-(2′-(diphenylphosphino)phenyl)-4,5-bis(carbomethoxy)-1,3,2-dioxaphospholane] ((2R,3R)-5) and (S)-[2-(diphenylphosphino)benzene][1,1′-binaphthalen-2,2′-diyl]phosphonite] ((S)-6). The analogous reaction of 4 with (1R,2S)-ephedrine using N-methylmorpholine as the base, gave [2-(2′-(diphenylphosphino)phenyl)-3,4-dimethyl-5-phenyl-1,3,2-oxazaphospholidine] (7) as a 95:5 mixture of diastereoisomers.     

Synthesis of 3 or 3,3′-substituted BINOL ligands and their application in the asymmetric addition of diethylzinc to aromatic aldehydes

Three new substituted BINOL ligands (R)-3-[4,6-bis(dimethylamino)-1,3,5-triazin-2-yl]-1,1′-bi-2-naphthol (R)-1, (R)-3,3′-bis[4,6-bis(dimethylamino)-1,3,5-triazin-2-yl]-1,1′-bi-2-naphthol (R)-2 and 2,4-bis(2,2′-dihydroxy-1,1′-binaphthalen-3-yl)-6-(p-tolyl)-1,3,5-triazine (R,R)-3 have been obtained by directed ortho-lithiation or Suzuki cross-coupling process. Ligand (R)-1 shows improved catalytic properties for the asymmetric diethylzinc addition to aromatic aldehydes.     

Synthesis and pharmacological evaluation of 5-[2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine derivatives as platelet aggregation inhibitors

One pot synthesis and characterization of new 5-[2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-4,5,6,7-tetrahydro-thieno[3,2-c]pyridines (3a–k) using amides (2a–k) were reported. The prepared 5-[2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine (3a) is a bioisostere of 4′-(6,7-dihydro-4H-thieno [3,2-c]pyridin-5-ylmethyl)-biphenyl-2-carboxylic acid (1), having good in vivo antithrombotic activity compared with Clopidogrel. The new tetrazole derivatives (3a–k) were screened for their in vitro activity as platelet aggregation inhibitors.     

A regioselective 1,3-dipolar cycloaddition for the synthesis of novel spiro-chromene thiadiazole derivatives

A variety of 4′-(4-R-phenyl)-4-(methylthio)-2′-phenyl-2′H-spiro[chromene-2,5′-[1,2,3]thiadiazole] 5a–d and 5′-(4-R-phenyl)-4-(methylthio)-3′-phenyl-3′H-spiro[chromene-2,2′-[1,3,4]thiadiazole] 6a–d were synthesized regioselectively through the reaction of 4-(methylthio)-2H-chromene-2-thione 2 with diarylnitrilimines under refluxing dry chloroform. Whilst the reaction of 4-(allylthio)-2H-chromene-2-thione 3 with diarylnitrilimines under similar reaction conditions afforded the corresponding 4-(allylthio)-5′-(4-R-phenyl)-3′-phenyl-3′H-spiro[chromene-2,2′-[1,3,4]thiadiazole] 7a–d and 5-(4-R-phenyl)-2′-methyl-3-phenyl-2′,3′-dihydro-3H-spiro[[1,3,4]thiadiazole-2,4′-thieno[3,2-c]chromene] 9a–d as two unisolable diastereoisomeric forms. The structures of the obtained spiro cycloadduct thiadiazoles have been assigned by means of spectroscopic measurements.     

New methodology for the synthesis of enantiopure (3R,2aR)-(−)-3-phenyl-hexahydro-oxazolo[3,2-a]-pyridin-5-one: a synthesis of (S)-(+)-coniine

A new and efficient methodology for the enantiopure synthesis of (3R,2aR)-(−)-3-phenyl-hexahydro-oxazolo[3,2-a]pyridin-5-one 3 starting from (1′R)-(−)-1-(2′-hydroxy-1′-phenyl-ethyl)-(1H)-pyridin-2-one 1 is described. In addition, the enantiospecific synthesis of (S)-(+)-coniine hydrochloride 6 in good yield from 3 is reported.     

Antimicrobial and antispasmodic tetrahydroanthracenes from Cassia singueana

Four tetrahydroanthracene derivatives with antimicrobial and antispasmodic activities have been isolated from Cassia singueana. The evidence described in the following indicates them to be torosachrysone (1), germichrysone (4), and two new dimeric tetrahydroanthracenes, singueanol-I (7) or 6,6′-dimethoxy-3, 3′,8,8′,9,9′-hexahydroxy-3,3′,7,7′-tetramethyl-3,3′,4,4′-tetrahydro(10,10′-bianthracen)-1,1′(2H,2′H)-dione, and singueanol-II (8) or 6,6′-dimethoxy-3,3′,8,8′,9,9′-hexahydroxy-3,3′,7,7′-tetramethyl-3,3′,4,4′-tetrahydro(5,10′-bianthracen)- 1′(2H,2′H)-dione.     

Efficient preparation of (1′R)-(−)-1-(2′-hydroxy-1′-phenylethyl)piperidin-2-one: synthesis of (2′S,3R)-(+)-stenusine

An efficient oxidation of (2′R)-(−)-2′-phenyl-2′-(piperidin-1-yl)ethanol 2 with bromine to generate the corresponding piperidin-2-one 3 in 96% is described. In addition, starting from 3, (2′S,3R)-(+)-stenusine 8 was synthesized in 70% overall yield. The X-ray analysis of piperidine 6·HCl is also reported.     

Synthesis of 1-(3′-deoxy-β-D-glycero-pentofuran-2′-ulosyl)uracil by selective elimination reactions

For the synthesis of y 1-(3′-deoxy-β-D-glycero-pentofuran-2′-ulosyl)uracil (16), the precursor, 5′-O-benzoyl derivative (2),² was elaborated in a variety of ways. 1-(5′-O-Benzoyl-3′-O-tosyl-β-D- lyxofuranosyl)uracil (4)² was benzoylated to N³-benzoyl-1-(2′,5′-di-O-benzoyl-3′-O-tosyl-β-D- lyxofuranosyl)uracil (5), which directly yielded 2 on treatment with sodium benzoate. 1-(3′,5′-Di-O- benzoyl-2′-O-tosyl-β-D-lyxofuranosyl)uracil (8) and its 3′,5′-O-isopropylidene analog (10) resisted elimination reactions, thus proving absolute selectivity in the elimination of the derivatives of 1-β-D- lyxofuranosyl-uracil. Seeking a more economical path to 2, 1-(5′-O-benzoyl-β-D-lyxofuranosyl)uracil (11) was first benzoylated to give 2′,5′-di-O-benzoate (12), accompanied by 3′,5′-di- and 2′,3′,5′-tri-O- benzoate. Mesylation of the major product (12) gave 1-(2′,5′-di-O-benzoyl-3′-O-mesyl-β-D- lyxofuranosyl)uracil (15), which, on treatment with sodium benzoate, gave 2 in an highly improved yield. Basic hydrolysis on 2 gave compound 16.     

Four new constituents from Taraxacum mongolicum

Two new flavone glycosides,isoetin-7-O-β-D-glucopyranosyl-2′-O-α-L-arabinopyranoside (1) and isoetin-7-O-β-D-glucopyr- anosyl-2′-O-α-D-glucopyranoside (2),a new lignan,mongolicumin A (3),and a new guaianolide,mongolicumin B (4) were isolated from the aerial part of Taraxacum mongolicum.Their structures were elucidated mainly by spectral analyses.     

Novel indan-1,3-dione derivatives: Design,green synthesis,effect against tomato damping-off disease caused by Fusarium oxysporum and in silico molecular docking study

An effective method for synthesizing series of twenty-two new compounds 1, 2a,b, 3, 4a,b, 5a-e, 7, 8, 9, 10, 12, 13a-d, 15a,b was performed starting from reaction of 1,2,3-indenetrione thiourea, and ethyl cyanoacetate under microwave irradiation and / or 2-(1,3-dioxo-1H-inden-2(3H)-ylidene) hydrazine carbothioamide with acetic anhydride. Chemical structure of the obtained products has been established by spectroscopic techniques including FTIR, ¹H NMR, ¹³C NMR, DEPT-135, and mass spectroscopy. The designed new compounds have been successfully examined in-vitro for their antifungal activities. The relation between the structure of the synthesized compounds and their activity against tomato damping-off disease caused by Fusarium oxysporum fungi was studied and favourable results were obtained. The antifungal studies indicated that compounds 1, 7, 4a and 5a-d exerted the highest antifungal activities, while 3 and 4b recorded the lowest effect. The obtained results confirmed the possibility of the application of ethyl 6′-amino-1,3-dioxo-2′-thioxo-1,2′,3,3′-tetrahydro-1′H-spiro[indene-2,4′-pyrimidine]-5′-carboxylate 1 as a new effective regulator of the vegetative growth of tomatoes. The molecular docking analysis was performed within succinate dehydrogenase (SDH) as a target enzyme in order to rationalize the promising findings obtained for the active compounds 1, 2a,b, 5a-d, 7, 8, 9, 10, 12, and 13a.     

Microwave-induced and conventional heterocyclic synthesis: An antimicrobial entites of newer quinazolinyl-Δ2-pyrazolines

Heterocyclic compounds containing pyrazolines were reported to possess significant biological activity. Synthesis of 2-(ω-chloroacetonyl)-3-p-fluorophenyl-6-bromoquinazoline-4(3H)-ones (2), 2-(ω-hydrazinoacetonyl)-3-p-fluorophenyl-6-bromoquinazoline-4(3H)-ones (3) and 1′-[3H-3-p-fluorophenyl-4-oxo-6-bromoquinazoline-2-acetonyl]-3′-[1-o-chlorophenyl-3-methyl-5-azomethine-2-pyrazolidene]-5′-(substituted phenyl)-Δ²-pyrazolines (4a–j) have been described. Some of the new compounds were tested against bacteria (Gram –ve and Gram +ve) and fungi.     

Synthesis and resolution of 2,2′-bis[di(p-tolyl)stibano]-1,1′-binaphthyl (BINASb); the first example of an optically active organoantimony ligand for asymmetric synthesis

Racemic 2,2′-bis[di(p-tolyl)stibano]-1,1′-binaphthyl (BINASb) (±)-2 has been prepared from 2,2′-dibromo-1,1′-binaphthyl 1 via 2,2′-dilithio-1,1′-binaphthyl intermediate, and has been resolved via the separation of a mixture of the diastereomeric Pd complexes 4A and 4B, derived from the reaction of (±)-2 with di-μ-chlorobis{(S)-2-[1-(dimethylamino)ethyl]phenyl-C,N}dipalladium(II) 3. The optically active BINASbs (S)-(+)-2 and (R)-(−)-2 have been shown to be effective chiral ligands for the rhodium-catalyzed asymmetric hydrosilylation of ketones.     

Synthesis of Schiff bases by aromatic amine condensation with 3,3′-bithiophenes-2,2′ and 4,4′-dicarbaldehydes

Reactions of aromatic amines with 3,3′-bithiophene-2,2′-dicarbaldehyde 1 and 3,3′-bithiophene-4,4′-dicarbaldehyde 2 gave the 2,2′-(N-(aryl)diimino)-3,3′-bithiophene 3 and 4,4′-(N-(aryl)diimino)-3,3′-bithiophene 4 in good yields. Orthophenylenediamine reacted with 1 and 2 to give dithieno[3,4-c;4′,3′-e]azepino[1,2-a]benzimidazole 5 and dithieno[2,3-c;3′,2′-e]azepino[1,2-a]benzimidazole 6. All these original products have been characterized by spectroscopic techniques and elemental analysis.     

Structures of six new compounds from Ligularia brassicoides

Four new eremophilane type sesquiterpenoids, a new bakkane type sesquiterpenoid, and a new secoeremophilane type sesquiterpenoid were isolated from Ligularia brassicoides Hand.-Mass. (Asteraceae) collected in China, and were an epoxy lactone derived from 6-acyloxyeuryopsin 1, 6-acyloxy-9-oxoeuryopsin 2, 6-acyloxy-9-oxofuranoeremophilane 3, 6-acyloxyeuryopsin 4, 6-acyloxy bakkane type epoxy lactone 5, and secovirgaurenol 6-O-(2′-hydroxymethyl)acrylate (6), respectively. All but one had a 2′-hydroxymethylacryloyloxy group at C-6. This is the first study to describe the chemical constituents of this species.     

Preparation and resolution of 2,2′-dimercapto-6,6′-dimethoxy-1,1′-biphenyl: a C2-symmetric sulfur building block

The preparation of the title dimercaptan 1 starting from 2,2′-dihydroxy-6,6′-dimethoxy-1,1′-biphenyl 2 is described. Resolution of dimercaptan 1 was performed using (−)-(1R,2S,5R)-menthyl chloroformate as a chiral resolving agent. The procedure affords dimercaptan (+)-1 and (−)-1 in 98% ee and 93% ee, respectively. A new and direct intermolecular Ullmann coupling resulting in an improved preparation of diol 2 is also reported.     

Novel NMR chiral solvating agents derived from (1R,2R)-diaminocyclohexane: synthesis and enantiodiscrimination for chiral carboxylic acids

A series of new compounds, (1R,2R)-1-(1′,8′-naphthalimide)-2-aminocyclohexane 1 and its 4′-derivatives 2 and 3 derived from (1R,2R)-1,2-diaminocyclohexane have been synthesized conveniently and efficiently. ¹H NMR spectroscopy was employed to investigate their enantiodiscriminating ability. Compared with α-phenylethylamine, a commercially available chiral solvating agent (CSA), these compounds exhibited better enantiodiscriminating ability toward the chiral carboxylic acids we had chosen, distinguishing them as promising and practical CSAs.     

Reduced collagen cross links: the first synthesis of all the possible (2S,2′S)-stereoisomers of 5-hydroxylysinonorleucine and of 5,5′-dihydroxylysinonorleucine in enantiomerically pure form

The paper reports the first enantioselective synthesis of all the possible collagen reduced cross links as described: (2S,2′S,5R)- and (2S,2′S,5S)-5-hydroxylysinonorleucine 3a and 3b, (2S,2′S,5R,5′R)-5,5′-dihydroxylysinonorleucine 4a, (2S,2′S,5R,5′S)-5,5′-dihydroxylysinonorleucine 4b and (2S,2′S,5S,5′S)-5,5′-dihydroxylysinonorleucine 4c. The Williams’ glycine template methodology was used both for the introduction of a stereogenic at the α-position and for an easy protection of the amino acidic functionalities during the synthesis of the dimeric amino acids.     

Total synthesis of optically active liverwort sesquiterpenes,trifarienols A and B,using phenylethylamine as a chiral auxiliary

The imine of (rac)-2,3-dimethylcyclohexanone 10a with (S)-(−)-phenylethylamine was reacted with methyl acrylate to yield methyl (1′S,6′R)-3-(1′,6′-dimethyl-2′-oxocyclohexyl)propanoate 4a in 26% (97% ee) after hydrolysis. When (2RS,3R)-2,3-dimethylcyclohexanone 10b was used, the same product 4b was obtained in 59% yield (>99.5% ee) after hydrolysis. When (2RS,3R)-2,3-dimethylcyclohexanone 10b and (R)-(+)-phenylethylamine were used, the reaction underwent in only 5% yield, the products being 4c, 12, 13, 14, and 15. Thus, the reaction of 3b with methyl acrylate is a matched case, while that of 3c is a mismatched case. These phenomena are explained by the nonbonded interaction of methyl acrylate with chiral phenylethylamine and the methyl group at the 6′-position of the cyclohexanone ring in the transition state. The propanoate product 4b was successfully transformed into liverwort sesquiterpene (+)-trifarienol A 1 and (−)-trifarienol B 2 in 10 steps. We have developed an HPLC method to determine the ees of 2,2-disubstituted and 2,2,3-trisubstituted cyclohexanones using the corresponding pentafluorophenyl esters.     

Preparation and use of MeO-PEG-supported chiral diphosphine ligands: soluble polymer-supported catalysts for asymmetric hydrogenation

Two new chiral MeO-PEG-supported (R)-BINAP and (3R,4R)-Pyrphos ligands were synthesized and employed in the Ru(II)- and Rh(I)-catalyzed asymmetric hydrogenation of 2-(6′-methoxy-2′-naphthyl)propenoic acid 5 and prochiral enamides 10. The results showed that these new soluble polymeric catalysts exhibited high catalytic activity and enantioselectivity. Enantiomeric excesses (e.e.s) in the ranges 90–96% and 86–96% were achieved in the hydrogenation of 5 and 10, respectively. Furthermore, these catalysts could be recovered easily and the recycled catalysts were shown to maintain their efficiency in subsequent reactions.     

Two new α,β-unsaturated butyrolactone derivatives from Pleione bulbocodioides

Two newα,β-unsaturated butyrolactone derivatives,4-(4″-hydroxybenzyl)-3-(3′-hydroxy-phenethyl)furan-2(5H)-one(1)and 3-(3′-hydroxyphenethyl)furan-2(5H)-one(2),together with one known phenolic compound(3),were isolated from the tubers of Pleione bulbocodioides(Franch.)Rolfe.Their structures were elucidated by analysis of spectroscopic data.