Multi-carbazole derivatives for two-photon absorption data storage: Synthesis, optical properties and theoretical calculation

Two novel quadrupolar organic compounds, 3-(4-((E)-2-(9-butyl-9H-carbazol-6-yl) vinyl)styryl)-9-propyl-9H-carbazole (BCSPC) and 3-(3-(3-((1E)-2-(4-((E)-2-(3-(3,5-bis(9-butyl-9H-carbazol-6-yl)phenyl)-9-butyl-9H-carbazol-6-yl)vinyl)phenyl) vinyl)-9-butyl-9H-carbazol-6-yl)-5-(9-butyl-9H-carbazol-6-yl)phenyl)-9-butyl-9H-carbazole (BCPBC), with different conjugated arms, have been designed and synthesized. Their one- and two-photon absorption (TPA) and excited fluorescence properties have been experimentally investigated. The two-photon absorption cross-sections of two compounds were estimated by two-photon excited fluorescence technique using 200 fs, 76 MHz, Ti:sapphire laser, which are 22 and 154 GM for BCSPC and BCPBC, respectively. The optimal excitation wavelengths are 780 nm for both BCSPC and BCPBC. A data recording experiment proved the potential application of the materials.     

Preparation of dimethyl (R)- and (S)-2-(2-aminophenyl)-2-hydroxyethylphosphonate from anthranilic acid

An efficient synthesis of both enantiomers of dimethyl δ-amino-β-hydroxyethylphosphonate 6 has been achieved starting from anthranilic acid, through the resolution of dimethyl (±)-2-(2-N,N-dibenzylaminophenyl)-2-hydroxyethylphosphonate 9 with (S)-O-methylmandelic acid. The absolute configuration of the enantiomers 9 was assigned by the Dale and Mosher approach using the extended Newman projections and molecular mechanics.     

Chirality sensing of saccharides using a boronic acid-appended chiral ferrocene derivative

A diboronic acid-appended chiral ferrocene derivative (R)-9 was designed and synthesized. This chiral ferrocene scaffold was obtained by resolution of the diastereomer with a monosaccharide derivative. One can therefore expect that (R)-9 would show d/l selectivity for specific monosaccharides. The complex formation of (R)-9 with various saccharides using the two boronic acid functions was conveniently monitored by a change in the circular dichroism (CD) spectra. The CD spectral change (Δ[θ]) induced by added monosaccharides was chiroselective: in particular, d/l-alloses and d/l-galactoses induced the 8.0- and 7.0-fold difference in the magnitude of the CD spectral change. The association constants for d- and l-saccharides (K_D and K_L, respectively) were determined: among them, (R)-9 showed a significant discrimination ability for mannose (K_L/K_D=2.6) and arabinose (K_L/K_D=1/2.4). The origin of d/l selectivity was discussed on the basis of computational studies on (R)-9·saccharide complexes.     

Synthesis of optically active β-hydroxy-β-polyfluoromethyl GABAs

A general synthetic route to polyfluoromethyl containing analogues of GABA—β-hydroxy-β-tri- and difluoromethyl GABAs 9a and 9b was developed, using the corresponding β-alkoxyvinyl polyfluoromethyl ketones—enones 1a and 1b as starting materials. Both enantiomers of the potential biologically active compound 9a were obtained by chiral resolution with (R)- or (S)-phenylethylamine.     

Photoaffinity labeling of bovine rhodopsin

Photoaffinity labeled (3-diazoacetoxy)-9-cis-retinal (1) and (9-methylenediazoacetoxy)-9-cis-retinal (20) were synthesized and bound to absorption maxima at 465 and 460 nm respectively. Binding studies established that synthetic retinals 1 and 2 bind to the natural binding site and that the integrity of the diazoacetoxy photoaffinity label is preserved in the process. Incorporation of 3-(O¹⁴COCHN₂)-labeled 9-cis retinal could be conveniently carried out in high yield using apomembrane solubilized in CHAPS as detergent to afford the pigment analog in a pure form. Photolysis of the diazoacetoxy group within the binding site led to 15–20%, crosslinking of rhodopsin as estimated by using radiocarbon containing labeled retinal 1 thus showing that this synthetic retinal is suitable for photoaffinity labeling of the active site in rhodopsin. Subsequent experiments to establish the site(s) of crosslinking by sequencing studies will then contribute to our knowledge of the structure of rhodopsin.     

Total synthesis of vernolepin—I : Synthesis of the key intermediate

The key intermediate (9) for the total synthesis of antitumor sesquiterpene vernolepin (1) was prepared in seventeen steps from 2,5-dihydroanisyl alcohol. Intramolecular Michael addition (7→ 8) afforded the cis-2-oxadecalone system, which was stereospecifically converted to 9 by using the enolization character of 8.     

Asymmetric Diels–Alder reaction using a new chiral β-nitroacrylate for enantiopure trans-β-norbornane amino acid preparation

The main nitronorbornene adduct derived from the asymmetric Diels–Alder reaction of (S)-benzyl-4-(3-(3-nitroacryloyloxy)-4,4-dimethyl-2-oxopyrrolidin-1-yl)benzoate (S)-1 and cyclopentadiene was isolated and transformed to afford the enantiopure bicyclic β-amino acid (1S,2R,3R,4R)-trans-β-norbornane amino acid 9. The enantiomer (1R,2S,3S,4S)-9 could be obtained by the same synthetic route by using the chiral auxiliary (R)-1.     

Functionalized enamines—XXII : Annelation of enamines of polycyclic α,β-unsaturated ketones; a facile partial synthesis of furano- indolo- and benzsteroids. Total synthesis of 3-oxa-A-norsteroid

Reaction of dienamine 4a with substituted phenacyl bromides gave steroidal[3,4-b] furans 5a–g. The same principle reaction was utilized for the total synthesis of (±) 2 - (p - chlorophenyl) - 3 - oxa - A - nor - estra - 1,5(10), 9(11) - triene - 17 - acetate 12a. Treatment of 4a, b with benzenediazonium salts, in DMF, followed by a Fischer-indole cyclization yielded steroidal[6, 7-b] indoles 8a–k. Dienamine 4b could be annelated to benz[4, 5, 6] steroids 9a and 9b by reaction with methyl vinyl ketone and crotonaldehyde, respectively.     

Practical method for crystalline-liquid resolution of chrysanthemic acids utilizing chiral 1,1′-binaphthol monoethyl ethers directed for process chemistry

We have developed an efficient practical resolution method for (1R,3R)-trans-chrysanthemic acid 1 and (1R,3S)-trans-2,2-dimethyl-3-(2,2-dichloroethenyl)cyclopropanecarboxylic acid 2, based on the preliminary results of the simpler analogues, (1R)-2,2-dichlorocyclopropanecarboxylic acid 3 and (1R)-2,2-dimethylcyclopropanecarboxylic acid 4, using a crystalline-liquid separation procedure (without column chromatography) with chiral 1,1′-binaphthol monoethyl ethers (R)-5b as the key auxiliary. Direct esterifications of 1, 2, 3, and 4 with (R)-5b gave four sets of (1R)- and (1S)-diastereomeric esters 8, 9, 6, and 7, respectively, with markedly different melting points. All of these diastereomers were easily obtained using a simple and one-step crystalline-liquid separation. The separated diastereomers 8 and 9 were easily hydrolyzed to the desired enantiopure acids 1 (>98%) and 2 (>99%), respectively, with recovery of (R)-5b (>90%).     

Synthesis of enantiomerically pure spiro-cyclopropane derivatives containing multichiral centers

A novel chiral source, 5-(R)-[(1R,2S,5R)-(−)-menthyloxy]-3-bromo-2(5H)-furanone (5a), was obtained in 46% yield with d.e.≥98% from the epimeric mixture of 5-(l-menthyloxy)-3-bromo-2(5H)-furanone (5a+5b) obtained via the bromination of an epimeric mixture of 5-(l-menthyloxy)-2(5H)-furanone (3a+3b) followed by the elimination of hydrogen bromide. The asymmetric reaction of 5a with a nucleophilic alcohol afforded enantiomerically pure spiro-cyclopropane derivatives containing four stereogenic centers, 9a–9e, in 50–68% yield with d.e.≥98%. The enantiomerically pure compounds 9a–9e were identified on the basis of their analytical data and spectroscopic data, such as [α]_D²⁰, UV, IR, ¹H NMR, ¹³C NMR, MS and elementary analysis. The absolute configuration of the chiral spiro-cyclopropane compound 9a was established by X-ray crystallography.     

Non-enzymatic diastereoselective asymmetric desymmetrization of 2-benzylserinols giving optically active 4-benzyl-4-hydroxymethyl-2-oxazolidinones: asymmetric syntheses of α-(hydroxymethyl)phenylalanine,N-Boc-α-methylphenylalanine,cericlamine and BIRT-377

A reaction of (S)-2-benzyl-2-(α-methylbenzyl)amino-1,3-propanediol (S)-4a and 2-chloroethyl chloroformate, and the subsequent addition of DBU gave (4R,αS)-4-benzyl-4-hydroxymethyl-3-(α-methylbenzyl)-2-oxazolidinone (4R)-5a (92% de) via a diastereoselective asymmetric desymmetrization process. Debenzylation of (4R)-5a using trifluoromethanesulfonic acid and anisole in MeNO₂ gave (R)-4-benzyl-4-hydroxymethyl-2-oxazolidinone (R)-15a, which was converted into (R)-(α-hydroxymethyl)phenylalanine (7) in two steps. N-Boc-α-methylphenylalanine (8), cericlami0ne (9) and BIRT-377 (10) were also synthesized using these asymmetric desymmetrization and debenzylation.     

Synthesis,characterization and biological activity of Hg(II), Fe(III) complexes with 1,3,4-oxadiazole, 1,2,4-triazole derivatives from L-methionine

Four novel heterocyclic1,3,4-oxadiazole, 1,2,4-triazole derivatives, namely: 5-[1-amino-3-(methylsulfanyl)propyl]-1,3,4-oxadiazole-2(3H)-thione (4), 4-amino-5-[1-amino-3-(methylsulfanyl)propyl]-4H-1,2,4-triazole-3-thiol (5), 1-amino-3-[1-amino-3-(methylsulfanyl)propyl]-1H-1,2,4-triazole-5-thiol (7), and 5-[1-amino-3-(methylsulfanyl)propyl]-1H-1,2,4-triazole-3-thiol (9) have been synthesized from l-methionine and characterized by different spectroscopic techniques (FT-IR, UV–Vis, ¹H NMR, ¹³C NMR and MS). Complex formation with Hg⁺⁺ and Fe⁺⁺⁺ ions were formed from the four heterocyclic 4, 5, 7 and 9. The antimicrobial activities for synthetic intermediates and final four products were assisted using paper disk diffusion method against Gram-negative bacteria: Escherichia coli, Pseudomonas aeroginosae and Gram-positive bacteria: Staphylococus aureus 25923, Staphylococus aureus 43300 and showed variant activity against some of the microorganisms tested.     

Resolution,absolute configuration and antifilarial activity of coumarinyl amino alcohols

The resolution of racemic coumarinyl amino alcohols 5–10 was achieved by using the inexpensive and readily accessible chiral resolving agent N-carbethoxy-l-proline (S)-11. Direct esterification of rac-5–10 with (S)-11 furnished diastereomeric esters, which were easily separated by column chromatography. The obtained diastereomers yielded the desired enantiopure coumarinyl amino alcohols (S)-(+)-5–10 and (R)-(?)-5–10 in good yields with high enantiomeric excess on saponification. The absolute configurations were determined by X-ray crystal analysis and/or by comparison of the specific rotations. Furthermore, in in vitro antifilarial motility inhibition assays, enantiopure coumarins (S)-(+)-9, (R)-(?)-9 and (S)-(+)-10, (R)-(?)-10 were found to be less efficient in affecting the viability of macrofilariae of Brugia malayi than their racemic forms 9 and 10, respectively, indicating the synergistic effect of the enantiomers in evoking antifilarial action.     

The influence of microwave irradiation on lipase-catalyzed kinetic resolution of racemic secondary alcohols

The influence of microwave irradiation on the Novozyme 435^® (Candida antarctica lipase) catalyzed kinetic resolution of secondary alcohols with different functional groups was studied in comparison to the use of conventional heating at 60 °C. p-Chlorophenyl acetate was used as an acyl donor and toluene as the solvent. (±)-1-Phenyl-1-propanol 1, (±)-1-(4-bromophenyl)-propan-1-ol 3, (±)-1-phenylbut-3-en-1-ol 5 and (±)-3-bromo-2-(2-hydroxypropyl)-1,4-dimethoxynaphthalene 7 were successfully resolved into their (S)-alcohols and (R)-esters, respectively, in good enantiomeric excess. Resolution of (±)-ethyl-5-(4-methoxybenyloxy)-3-hydroxypentanoate 9 afforded its (R)-alcohol and (S)-ester using this method. In addition, microwave-assisted lipase transesterification of meso-symmetric diol 11 effected desymmetrization to ester 12 with high enantiomeric excess. In all cases studied, the conversion value for the microwave-assisted lipase kinetic resolution of secondary alcohols was higher than that obtained using conventional heating.     

Asymmetric azo-ene reactions using the chiral azo-enophile di-(−)-(1R,2S)-2-phenyl-1-cyclohexyl diazenedicarboxylate

The preparation of di-(−)-(1R,2S)-2-phenyl-1-cyclohexyl diazenedicarboxylate 4 is described. Reaction of (1R,2S)-2-phenyl-1-cyclohexanol 1 with excess phosgene in the presence of quinoline afforded chloroformate 2 which was treated directly with hydrazine monohydrate (0.5 equiv.) to afford di-(−)-(1R,2S)-2-phenyl-1-cyclohexyl diazanedicarboxylate 3. Oxidization of 3 to the azo-enophile 4 was then readily effected in high yield using N-bromosuccinimide and pyridine. The azo-ene reactions of 4 with the alkenes cyclohexene 5, cyclopentene 6, trans-3-hexene 7 and trans-4-octene 8 were carried out using the Lewis acid tin(IV) chloride. Use of cyclohexene 5 afforded the ene adduct 9 in 80% yield with a diastereomeric excess of >97:3 whilst the use of cyclopentene 6, trans-3-hexene 7 and trans-4-octene 8 afforded the ene adducts 10 (77%), 11 (71%) and 12 (92%) with a diastereomeric excess of 86:14 in each case. Use of the conjugated aromatic acyclic alkene 13 afforded the product of an ionic addition, namely, chloride 14 in 57% yield. Cleavage of the N–N bond of the ene adduct 9 was effected using lithium in liquid ammonia affording the carbamate 16 in moderate yield.     

Asymmetric [2,3] Wittig rearrangement of crotyl furfuryl ethers

Asymmetric Wittig rearrangement of crotyl furfuryl ethers was investigated in diastereo- and enantioselective manners. Both (2S,3Z)- and (2S,3E)-3-penten-2-yl furfuryl ethers 3 and 9 rearranged with complete chirality transfer to give the syn- and anti-isomers 4 and 10, respectively. Enantioselective Wittig rearrangement of both (Z)-and (E)-crotyl furfuryl ethers 15 and 17 using butyllithium and (−)-sparteine was examined to afford (1S,2R)-1-(2-furyl)-2-methyl-3-buten-ol 16 in up to 43% ee.     

Convenient construction of a variety of glycosidic linkages using a universal glucosyl donor

This letter deals with the concept of constructing four types (cis-α, trans-α, cis-β, and trans-β) of glycosidic linkages using a universal glucosyl donor. The selectively protected universal glucosyl donor 8 was synthesized in 36% yield from d-glucose (eight steps). The donor 8 undergoes glycosidation with a primary carbohydrate alcohol 7 to give disaccharide 9 having a 1,2-cis-α-glycosidic linkage in 90% yield. The construction of the corresponding 1,2-trans-α-glycosidic linkage was performed in 68% yield (three steps) from 9. A similar glycosidation of the 2-O-(N-phenylcarbamoyl)-glucosyl donor 6 derived from 8 with 7 gave disaccharide 11 having a 1,2-trans-β-glycosidic linkage in 75% yield. The construction of the corresponding 1,2-cis-β-linkage was performed in 53% yield (three steps) from 11.     

Tri- and tetrasubstituted α-fluorocyclohexanones with enantiomeric excesses in the range of 97–100%

The α-fluorinated trisubstituted ketones (2S,5R)-(−)-7-Ia, (2R,5R)-(+)-7-IIe, (2S,5R)-(−)-8-Ia and (2R,5R)-(+)-8-IIe were synthesised from (+)-dihydrocarvone (99% (R)-configuration at C-5) and fully characterised. α-Fluorinated tetrasubstituted ketones (−)-9-Ia, (+)-9-Ia, (+)-9-IIa and (+)-10-Ia having e.e.s of ≥97% were synthesised as racemates from 3-methyl cyclohexenone then resolved into the pure enantiomers using chiral HPLC and fully characterised.     

Syntheses of methylene-bridged ansa-zirconocene complexes and copolymerization studies of ethylene and norbornene

Methylene-bridged ansa-metallocene complexes bearing substituents on the cyclopentadienyl (Cp) and fluorenyl (Flu) moieties, namely methylene[9-(2,7-di-tert-butyl)fluorenyl(2-(1,3-dimethylcyclopentadienyl))]zirconium dichloride (1a) and its analogue, methylene[(9-(2,7-di-tert-butyl)fluorenyl(2-(1-methyl-3-phenyl)cyclopentadienyl))]zirconium dichloride (2a), have been prepared from (2,7-di-tert-butyl)-9-prop-2-ynyl-9H-fluorene (2). This procedure includes the use of 3-bromo-1-propyne which affords the methylene bridging unit by way of an intermolecular Pauson-Khand reaction in which norbornadiene and a pendant alkyne cyclize to form a ring that later becomes a substituted cyclopentadienyl group. Ethylene-norbornene (E-N) copolymerization was then carried out using these new complexes (1a and 1b) in the presence of methylaluminoxane (MAO) as a cocatalyst; these activities can be compared to that of isopropylene[9-fluorenyl-cyclopentadienyl]zirconium dichloride (3a). The activity of catalyst 1a was comparable to that of 3a but much higher than that of 2a. In addition, 1a shows higher norbornene insertion performance, and gives an E-N copolymer with a higher glass transition temperature (T_g) than 2a under identical conditions; both 1a and 2a give a lower T_g polymer than 3a does.     

Synthesis of 2,3,4-trideoxy-4-c-(phenylphosphinyl)-dl-glycero-pentofuranose and its 1,5-diacetate

Synthesis of 2,3,4-trideoxy-4-C-(phenylphosphinyl)-dl-glycero-pentofuranose (11) starting from 2-furanmethanol was successful. The reaction of methyl 2,3-dideoxy-(1S)-dl-pentopyranosid-4-ulose 4-(p-toluenesulfonylhydrazone) with methyl phenylphosphonite gave methyl (4RS)-2,3,4-trideoxy-4-C-[(methoxy)phenylphosphinyl]-4-C-(p-toluenesulfonylhydrazino)-(1S)-dl-pentopyranoside (7), which on treatment with sodium borohydride afforded methyl 2,3,4-trideoxy-4-C-[(methoxy)phenylphosphinyl]-(1S)-dl-glycero-pentopyranoside (9). Treatment of compound 9 with SDMA followed by hydrolysis and treatment with acetic anhydride-pyridine afforded 1,5-diacetate 12 of compound 11.