Synthesis of regioisomeric,stereoregular AABB-type polyamides from chiral diamines and diacids derived from natural amino acids

Two regioisomeric and stereoregular AABB-type polyamides have been synthesized using l-glutamic acid 1 and l-alaninol 4 as sources of chirality. From 4, two derivatives of chiral diamines were prepared and regioselectively condensed with pentachlorophenyl 5-oxo-(S)-2-tetrahydrofurancarboxylate 3, derived from 1. Manipulation of functional groups and convenient deprotections led to the ammonium salts of N-[1′-amino-(S)-2′-propyl]- and N-[(S)-2′-amino-1′-propyl]-5-oxo-(S)-2-tetrahydrofurancarboxyamide 11 and 15, respectively, in which the building blocks derived from 1 and 4 are linked through an amido group. Compounds 11 and 15 are, in fact, α,ω-amino acids having amino and lactone groups, and hence activated for polycondensation. Thus, polymerization of 11 took place under regio- and stereo-control to afford stereoregular poly[N-(1′-amino-(S)-2′-propyl)-carboxyamido-(S)-2-hydroxypentan-5-oic acid] (16). Similar polycondensation of 15, under the optimized conditions employed for the synthesis of 16, gave the regioisomeric polyamide 17, which exhibited a molecular weight lower than that of 16. The thermal and spectroscopic properties of optically active AABB-polyamides 16 and 17 are described.     

Antifungal diastereomeric furanones from Mutisia friesiana: structural determination and conformational analysis

Two diastereomeric furanones, (4S,5S)-5-(4′-methyl-3′-pentenyl)-4-hydroxy-5-methyldihydrofuran-2-one 1 and (4S,5R)-5-(4′-methyl-3′-pentenyl)-4-hydroxy-5-methyldihydrofuran-2-one 2 were isolated for the first time from the shrub Mutisia friesiana. The relative stereochemistries of 1 and 2 were ascertained from NOESY NMR data and confirmed by a combination of molecular modeling (molecular mechanics and ab initio molecular orbital calculations) and NMR data. Comparison between experimental and calculated ¹H–¹H vicinal coupling constants revealed that both furanones exist in an equilibrium of two stable conformers of the five-membered ring. Application of Mosher's method suggests that both diastereomeric furanones have the same (S)-configuration at C-(4) and are epimers at C-(5). Furanones 1 and 2 showed antifungal activity against the pathogenic fungus Cladosporium cucumerinum.     

2,2′-Dihydroxy-3,3′-dimethoxy-5,5′-dimethyl-6,6′-dibromo-1,1′-biphenyl: preparation,resolution, structure and biological activity

The preparation and resolution of the titled conformationally stable biphenyl 1 has been performed in high chemical yield starting from creosol 2. Enantiopure biphenyls (aR)-(+)-1 and (aS)-(−)-1 were obtained by the corresponding menthylcarbonate diastereomer and successive reduction. The absolute configuration and specific rotation were correlated by X-ray analysis of the crystal structure of diastereopure menthylcarbonate (aS,1R,1′R,2S,2′S,5R,5′R)-(+)-16. Preliminary biological evaluation of both racemic enantiomers of 1 has been carried out on melanoma cell lines and significant and selective anticancer activity has been observed for the enantiomer (aS)-(−)-1.     

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.     

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.     

Reaktion der Tautomeren 4-Hydroxy-2H-thiopyran-2-thion und 2-Mercapto-4H-thiopyran-4-on mit aliphatischen Aldehyden

5,6-Dihydro-4-hydroxy-6,6-dimethyl-2H-thiopyrane-2-thione (1 I) and its tautomer 2-mercapto-4H-thiopyrane-4-one (1 II) react with aliphatic aldehydes under different reaction conditions to yield mainly 5R-7,8-dihydro-2H,5H,6H-thiopyrano[2,3—b:6,5—b′]-bisthiopyran-4,6(3H)-diones2 and 2′R,4′R-5,6,6′,7′-tetrahydro-2-thioxo-spiro(4H-thiopyran-3(2H), 3′(4′H)-2′H,5′H-thiopyrano-[2,3—b]-thiopyran)-4,5′-diones3. The mechanisms of formation of the condensates2 and3 and their stereochemistry are discussed. The reaction yielding2 is analogous to the condensation of dimedone with subsequent anhydride formation.3 might be generated byDiels-Adler reaction of intermediately formed 2-thioxo-3-alkylidenethiopyranones4. An X-ray crystal structure analysis was carried out on3 b to establish its configuration and conformation.     

trans-Aconitic acid-based hetero-Diels-Alder reaction in the synthesis of thiopyrano[2,3-d][1,3]thiazole derivatives

The hetero-Diels-Alder reaction of 5-arylideneisorhodanines with trans-aconitic acid proceeds as a regio- and diastereoselective process with spontaneous decarboxylation of the [4+2]-adduct to furnish thiopyrano[2,3-d][1,3]thiazole (2) and chromeno[4′,3′:4,5]thiopyrano[2,3-d]thiazole (3) derivatives analogously to the use of itaconic acid as a dienophile. Conversely, the one-pot, three-component reaction of 5-arylideneisorhodanines, trans-aconitic acid and anilines proceeded without decarboxylation, leading to novel rel-(5′R,6′R,7′R)-5′-carboxy-7′-aryl-1-aryl-3′,7′-dihydro-2H,2′H,5H-spiro[pyrrolidin-3,6′-thiopyrano[2,3-d]thiazol]-2,2′,5-triones 4. Interestingly, the use of trans-aconitic acid trimethyl ester led to the opposite regioselectivity, yielding rel-(5R,6S,7S)-5-methyloxycarbonylmethyl-2-oxo-7-aryl-3,5,6,7-tetrahydro-2H-thiopyrano[2,3-d]thiazol-5,6-dicarboxylates 5. Selected compounds were examined for trypanocide activity against the bloodstream forms of Trypanosoma brucei where compound 4e showed the highest activity (IC₅₀ = 6.74 μM).     

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.     

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.     

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.     

Excited state intramolecular hydrogen atom transfer of phenylethynyl-substituted 2′-hydroxychalcones

(E)-1-[2-Hydroxy-4-(phenylethynyl)phenyl]-3-[4-(phenylethynyl)phenyl]prop-2-en-1-one (1), (E)-1-[2-hydroxy-4-(phenylethynyl)phenyl]-3-phenylprop-2-en-1-one (2), and (E)-1-(2-hydroxyphenyl)-3-[4-(phenylethynyl)phenyl]prop-2-en-1-one (3), which belong to a new class of 2′-hydroxychalcones with phenylethynyl group(s) at the para position of the phenyl ring, were synthesized, and their photochemical properties were investigated. The lowest energy absorption band of 1 peaks at a longer wavelength (383 nm) with a much larger molar extinction coefficient (5.0 × 10⁴ M ^?1 cm^?1) than that of the parent 2′-hydroxychalcone (2′HC) (2.0 × 10⁴ M ^?1 cm^?1 at 318 nm). Upon photoexcitation, all three compounds underwent excited-state intramolecular hydrogen atom transfer (ESIHT) to produce an excited tautomer that emitted fluorescence with a large Stokes shift in the longer wavelength region at 600–700 nm. The quantum yield of the tautomer fluorescence of 1 was not high at 298 K (Φ _f = 9.1 × 10^?5), but was highest among 2′HC and its analogues. The Φ _f values of 1–3 increased 10–30 fold upon reducing the temperature from 298 to 77 K.     

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.     

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.     

Metal complexes with pyridone-based radicals: Preparation and properties of a dinuclear paddle-wheel copper(II) complex and a mononuclear palladium(II) complex

We prepared and characterized dinuclear copper(II) and mononuclear palladium(II) complexes coordinated with a pyridine-based open-shell ligand, 5-(4′,4′,5′,5′-tetramethylimidazoline-3′-oxide-1′-oxyl)-2(1H)-pyridone (=HL). In the copper(II) dinuclear complex [Cu₂(L)₄(DMF)₂] (1), four deprotonated ligands are coordinated as bridging ligands to form a paddle-wheel type unit. In the palladium(II) complex trans-[PdCl₂(HL)₂] (2), two HL ligands in the neutral hydroxypyridine form are coordinated to the trans positions of the metal ion via the nitrogen atoms. The hydroxyl groups of the ligands are hydrogen-bonded to the chlorine atoms of neighboring molecules, thereby creating a hydrogen-bonded double-chain molecular arrangement. Magnetic susceptibilities of these complexes were measured and analyzed. The small intramolecular antiferromagnetic interaction in the latter complex may originate from superexchange through the diamagnetic metal center.     

Design,synthesis and biological evaluation of novel isoniazid hybrids

We herein report the design and synthesis of novel isoniazid derivatives. Isoniazid derived Schiff bases (3 a-d) were subjected to cyclization with acetic anhydride and sulphuric acid to yield the 5′-substituted-3′-acetyl-5-(pyridin-4-yl)-3H-spiro[indole-3, 2-[1′, 3′, 4’]oxadiazol]-2′-yl acetates (4 a-d) and 8′-substituted-3’-(pyridin-4-yl)[1′,3′,4’]oxadiazino [6,5-b]indoles (5 a-d) respectively. The advantages of spectral methods were used for the confirmation of the structure of all the newly synthesized hybrid molecules. Further, these compounds were evaluated for their antibacterial activity against B. Subtilis, S. aureus, E. coli & S. typhi, antifungal activity against C. albicans, C. oxysporum, A. Flavus & A. niger, and antimycobacterial activity against M. tuberculosis. Amongst, the compounds 4b, 4c and 5c showed excellent inhibitory activity against tested microorganisms. Also, the DNA cleavage activity of selected compounds was carried out by the AGE method.     

Synthesis of (−)-(1′S,4aS,8aR)- and (+)-(1′S,4aR,8aS)-4a-ethyl-1-(1′-phenylethyl)-octahydroquinolin-7-ones

A synthesis of the enamine (−)-(1′S)-5-ethyl-1-(1′-phenylethyl)-1,2,3,4-tetrahydropyridine 4 and its application in a synthesis of (−)-(1′S,4aS,8aR)- and (+)-(1′S,4aR,8aS)-4a-ethyl-1-(1′-phenylethyl)-octahydroquinolin-7-ones 5 and 6 is described. In addition, an X-ray study of 6 is reported. Finally, the preparation of (+)-(4aS,8aR)-4a-ethyl-octahydroquinolin-7-one 7 is described.     

Tetra-tert-butyl-pentafulvalen als Ligand in zweikernigen Molybdänkomplexen: cis-Anordnung ohne Metall-Metall-bindung

Reaction of 1,1′,3,3′-tetra-tert-butyl-5-′-pentafulvalenedipotassium (1) with hexacarbonylmolybdenum leads to hexacarbonyl-dipotassium(1,1′,3,′-tetra-tert-butyl-5,5′-pemtafulvalene)dimolybdate (2), which on further treatment with stoichiometric amounts of iodomethane yields the hexacarbonyldimethyl(1,1′-3,3′-tetra-tert-butyl-5,5′-pentafulvalene)dimolybdenum, (η⁵ : η⁵-^tBu₄C₁₀H₄)Mo₂(CO)₆-(CH)₃)₂ (3). Compound 3 is obtained as yellow needles and brownish cube-like crystals, and it is characterized by ¹H-NMR, ¹³C-NMR, IR, and MS data. The cubes crystallize in the space group C2/c with four molecules in the unit cell. Each molecule consists of two tricarbonylmethyl(cyclopentadienyl) molybdenum units which are connected by a central CC-bond, twisted against each other by 64.8° and bent by 25.8°. Due to the steric requirements of the tertbutyl substituents in the fulvalene ligand, 3 should be formed only from cis-configurated 2.     

Codonocarpus alkaloids—IV : Synthesis of 2-methoxy-2′-ethoxy-4-[2-(tetramethylenecarbamoyl)ethyl]-5′-[2-(propylcarbamoyl)ethyl]diphenyl ether

Synthesis of the title compound was accomplished by coupling the iodonium bromide (3) of 4-ethoxybenzaldehyde with methyl hydroferulate (4) to 2-methoxy-2′-ethoxy-4-(methyl β-propionate)-5′-formyldiphenyl ether (5) which was converted to the pyrrolidinyl amide 6, and then the aryl aldehyde group was extended to a n-propyl β-propionamide unit via the Knoevenagel malonic acid reaction through the trans-cinnamic acid 7 followed by hydrogenation and amide formation with n-propylamine.     

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.     

Zur Reaktion des Dihydro-6-methyl-4-phenyl-2(1H)-pyrimidinthions mit Formaldehyd und Aminen

Dihydro-6-methyl-4-phenyl-2(1H)-pyrimidinthione (1 a) reacts with formaldehyde and amines to 6-(2′-dialkylaminoethyliden)-tetrahydro-resp. 6-(2′-dialkylaminoethyliden)-tetrahydro-5-dialkylaminomethyl-2(1H)-pyrimidinthiones (2) as well as 6-alkyloctahydro-8a-ethoxy- resp. hydroxypyrido-[4,3-d]-pyrimidine-2(1H)-thiones (5).