Ring‐Opening Reactions of 3‐Aryl‐1‐benzylaziridine‐2‐carboxylates and Application to the Asymmetric Synthesis of an Amphetamine‐Type Compound

Nucleophilic ring‐opening reactions of 3‐aryl‐1‐benzylaziridine‐2‐carboxylates were examined by using O‐nucleophiles and aromatic C‐nucleophiles. The stereospecificity was found to depend on substrates and conditions used. Configuration inversion at C(3) was observed with O‐nucleophiles as a major reaction path in the ring‐opening reactions of aziridines carrying an electron‐poor aromatic moiety, whereas mixtures containing preferentially the syn‐diastereoisomer were generally obtained when electron‐rich aziridines were used (Tables 1–3). In the reactions of electron‐rich aziridines with C‐nucleophiles, S_N2 reactions yielding anti‐type products were observed (Table 4). Reductive ring‐opening reaction by catalytic hydrogenation of (+)‐trans‐(2S,3R)‐3‐(1,3‐benzodioxol‐5‐yl)aziridine‐2‐carboxylate (+)‐trans‐ 3c afforded the corresponding α‐amino acid derivative, which was smoothly transformed into (+)‐tert‐butyl [(1R)‐2‐(1,3‐benzodioxol‐5‐yl)‐1‐methylethyl]carbamate((+)‐ 14 ) with high retention of optical purity (Scheme 6).     

Megastigmane Glycosides from Docynia indica and Their Anti‐inflammatory Activities

Using various chromatographic methods, three new megastigmane glycosides, docynicasides A – C ( 1  –  3 ) and ten known, (6S,9R)‐vomifoliol 9‐O‐β‐d ‐xylopyranosyl‐(1′′→6′)‐O‐β‐d ‐glucopyranoside ( 4 ), hyperin ( 5 ), quercitrin ( 6 ), quercetin 3‐α‐l ‐arabinofuranoside ( 7 ), naringenin 7‐O‐β‐d ‐glucopyranoside ( 8 ), phloridzin ( 9 ), phloretin 2′‐O‐β‐d ‐xylopyranosyl‐(1→6)‐β‐d ‐glucopyranoside ( 10 ), pinosylvin 3‐O‐β‐d ‐glucopyranoside ( 11 ), tormentic acid ( 12 ), and chlorogenic acid methyl ester ( 13 ) were isolated from the fruits of Docynia indica. Their chemical structures were elucidated by physical and chemical methods. All the isolated compounds were evaluated for the inhibitory activity on NO production in LPS‐stimulated BV2 cells. As the results, compounds 3  –  5 showed significant inhibitory activity on LPS‐stimulated NO production in BV2 cells with the IC₅₀ values ranging from 21.0 to 29.3 μm .     

Polar Constituents from Sageretia Thea Leaf Characterized by HPLC‐SPE‐NMR Assisted Approaches

Nine glycosides ( 1–9 ) were characterized from the n‐butanol‐soluble fraction of the ethanolic extract of the leaves of Sageretia thea by the general approach. Among these, Compounds 6 and 7 were identified as a mixture. Application of HPLC‐SPE‐NMR in two selected fractions led to the separation of this mixture and the characterization of three additional minors ( 10–12 ). Among these, 7‐O‐methylmyricetin 3‐O‐α‐l ‐arabinofuranoside ( 8 ) is a new natural product and eight compounds, i.e. glucofragulin A ( 1 ), quercetin‐3‐O‐α‐l ‐arabinopyranoside ( 5 ), 3‐O‐β‐d ‐galactopyranoside ( 6 ), 3‐O‐β‐d ‐glucopyranoside ( 7 ), and 3‐O‐α‐l ‐arabinofuranoside ( 11 ), myricetin‐3‐O‐α‐l ‐arabinofuranoside ( 9 ) and 3‐O‐β‐d‐glucopyranoside ( 10 ), and quercetrin ( 12 ), are found for the first time from the title plant.     

New Cycloartane and Flavonol Glycosides from Corchorus depressus

Two new monodesmosidic cycloartane triterpene glycosides, depressosides E and F, and two new flavonol glycosides, depressonol A and B, were isolated from the butanol‐soluble part of the EtOH extract of Corchorus depressus L . The structures of the new compounds were elucidated as (22R,24S)‐22,25‐epoxy‐9,19‐cyclolanostane‐3β,16β,24‐triol 3‐[α‐L ‐rhamnopyranosyl‐(1→4)‐β‐D ‐glucopyranoside] ( 1 ), (22R,24S)‐22,25‐epoxy‐9,19‐cyclolanostane‐3β,16β,24‐triol 3‐[α‐D ‐glucopyranosyl‐(1→3)‐β‐D ‐glucopyranoside] ( 2 ), kaempferol 3‐[β‐D ‐glucopyranosyl‐(1→4)‐β‐D ‐galactopyranoside] 7‐[α‐L ‐arabinofuranoside] ( 4 ), and kaempferol 3‐[β‐D ‐glucopyranosyl‐(1→6)‐β‐D ‐galactopyranoside] 7‐[α‐L ‐arabinofuranoside] ( 5 ) on the basis of chemical evidence and detailed spectroscopic studies.     

Synthesis of the Spermidine Alkaloids (−)‐(2R,3R)‐ and (−)‐(2R,3S)‐3‐Hydroxycelacinnine: Macrocyclization with Oxirane‐Ring Opening and Inversion via Cyclic Sulfamidates

The two epimers (?)‐ 1a and (?)‐ 1b of the macrocyclic lactam alkaloid 3‐hydroxycelacinnine with the (2R,3R) and (2R,3S) absolute configurations, respectively, were synthesized by an alternative route involving macrocyclization with the regio‐ and stereoselective oxirane‐ring opening by the terminal amino group (Schemes 2 and 6). Properly N‐protected chiral trans‐oxirane precursors provided (2R,3R)‐macrocycles after a one‐pot deprotection‐macrocyclization step under moderate dilution (0.005–0.01M ). The best yields (65–85%) were achieved with trifluoroacetyl protection. Macrocyclization of the corresponding cis‐oxiranes was unsuccessful for steric reasons. Inversion at OH? C(3) via nucleophilic displacement of the cyclic sulfamidate derivative with NaNO₂ led to (2R,3S)‐macrocycles. The synthesized (?)‐(2R,3S)‐3‐hydroxycelacinnine ((?)‐ 1b ) was identical to the natural alkaloid.     

Concentration effects in the cationic ring‐opening polymerization of 2‐ethyl‐2‐oxazoline in N,N‐dimethylacetamide

The monomer concentration for the cationic ring‐opening polymerization of 2‐ethyl‐2‐oxazoline in N,N‐dimethylacetamide was optimized utilizing high‐throughput experimentation methods. Detailed ¹H‐NMR spectroscopic investigations were performed to understand the mechanistic aspects of the observed concentration effects. Finally, the improved polymerization concentration was applied for the synthesis of higher molecular weight (> 10,000 Da) poly(2‐ethyl‐2‐oxazoline)s. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1487–1497, 2005     

New palladium(II)–N‐heterocyclic carbene complexes containing benzimidazole‐2‐ylidene ligand derived from menthol: synthesis,characterization and catalytic activities

A new series of sterically hindered ligands containing (1R,2S,4R)‐(+)‐menthoxymethyl group attached to benzimidazole‐based N‐heterocyclic carbene (NHC), palladium–bis‐NHC complexes and (κ²‐C,N)‐palladacyclic NHC complexes have been synthesized and characterized using appropriate spectroscopic techniques. Catalytic performance of the palladium complexes has been investigated for allylic alkylation, Suzuki and Heck carbon–carbon coupling reactions. These complexes smoothly catalyse the carbon–carbon bond formation reactions. Copyright © 2016 John Wiley & Sons, Ltd.     

An Efficient Synthesis of Optically Active trans‐(3R,4R)‐3‐Acetoxy‐4‐aryl‐1‐(chrysen‐6‐yl)azetidin‐2‐ones Using (+)‐Car‐3‐ene as a Chiral Auxiliary

An efficient enantioselective synthesis of 3‐acetoxy trans‐β‐lactams 7a and 7b via [2+2] cycloaddition reactions of imines 4a and 4b , derived from a polycyclic aromatic amine and bicyclic chiral acid obtained from (+)‐car‐3‐ene, is described. The cycloaddition was found to be highly enantioselective, producing only trans‐(3R,4R)‐N‐azetidin‐2‐one in very good yields. This is the first report of the synthesis of enantiomerically pure trans‐β‐lactams 7a and 7b with a polycyclic aromatic substituent at N(1) of the azetidin ring.     

Anionic ring‐opening polymerization of a five‐membered cyclic urethane derived from d‐glucosamine

The anionic ring‐opening polymerization of a five‐membered cyclic urethane, 2‐amino‐4,6‐O‐benzylidene‐2‐N,3‐O‐carbonyl‐2‐deoxy‐α,d ‐glucopyranoside (MBUG), which was prepared from naturally abundant d ‐glucosamine, was examined. Potassium tert‐butoxide (t‐BuOK) was the most effective initiator among the evaluated bases and produced polyurethane with the Mn of 7800 without any elimination of CO₂. The equimolar reaction of MBUG and t‐BuOK in the presence of CH₃I produced N‐methylated MBUG and suggested that the initiation reaction involves proton abstraction from the NH group. This N‐methylated compound did not undergo the polymerization. Therefore, the mechanism of propagation in the ROP of MBUG should involve the proton abstraction and nucleophilic substitution of the resulting amide anion. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 2491–2497     

Syntheses and Glycosidase Inhibitory Activities of 2‐(Aminomethyl)‐5‐(hydroxymethyl)pyrrolidine‐3,4‐diol Derivatives

New 2‐(aminomethyl)‐5‐(hydroxymethyl)pyrrolidine‐3,4‐diol derivatives were synthesized from (5S)‐5‐[(trityloxy)methyl]pyrrolidin‐2‐one ( 6 ) (Schemes 1 and 2) and their inhibitory activities toward 25 glycosidases assayed (Table). The influence of the configuration of the pyrrolidine ring on glycosidase inhibition was evaluated. (2R,3R,4S,5R)‐2‐[(benzylamino)methyl]‐5‐(hydroxymethyl)pyrrolidine‐3,4‐diol ((+)‐ 21 ) was found to be a good and selective inhibitor of α‐mannosidase from jack bean (K_i=1.2 μM ) and from almond (K_i=1.0 μM ). Selectivity was lost for the non‐benzylated derivative (2R,3R,4S,5R)‐2‐(aminomethyl)‐5‐(hydroxymethyl)pyrrolidine‐3,4‐diol ((+)‐ 22 ) which inhibited α‐galactosidases, β‐galactosidases, β‐glucosidases, and α‐N‐acetylgalactosaminidase as well.     

Di‐ and tri‐organotin derivatives of 3S,4S‐3‐[(R)‐1‐(tert‐butyl‐dimethylsilyloxy)ethyl]‐4‐[(R)‐1‐carboxyethyl]‐2‐azetidinone: synthesis,characterization and in vitro antitumour activity

Di‐n‐butyl‐, triphenyl and tri‐n‐butyltin derivatives of 3 S, 4 S ‐3‐[( R )‐1‐(tert‐butyldimethyl‐­<?tw=103.5%>silyloxy)ethyl‐4‐[( R )‐1‐carboxyethyl]‐2‐azetidi<?tw>‐­none were synthesized and characterized. Their antitumour activity was screened against seven tumoural cell lines of human origin. Copyright © 1999 John Wiley & Sons, Ltd.     

5‐Hydroxyalkyl derivatives of tert‐butyl 2‐oxo‐2,5‐dihydro‐1H‐pyrrole‐1‐carboxylate: diastereoselectivity of the Mukaiyama crossed‐aldol‐type reaction

The title compounds, rac‐(1′R,2R)‐tert‐butyl 2‐(1′‐hydroxyethyl)‐3‐(2‐nitrophenyl)‐5‐oxo‐2,5‐dihydro‐1H‐pyrrole‐1‐carboxylate, C₁₇H₂₀N₂O₆, (I), rac‐(1′S,2R)‐tert‐butyl 2‐[1′‐hydroxy‐3′‐(methoxycarbonyl)propyl]‐3‐(2‐nitrophenyl)‐5‐oxo‐2,5‐dihydro‐1H‐pyrrole‐1‐carboxylate, C₂₀H₂₄N₂O₈, (II), and rac‐(1′S,2R)‐tert‐butyl 2‐(4′‐bromo‐1′‐hydroxybutyl)‐5‐oxo‐2,5‐dihydro‐1H‐pyrrole‐1‐carboxylate, C₁₃H₂₀BrNO₄, (III), are 5‐hydroxyalkyl derivatives of tert‐butyl 2‐oxo‐2,5‐dihydropyrrole‐1‐carboxylate. In all three compounds, the tert‐butoxycarbonyl (Boc) unit is orientated in the same manner with respect to the mean plane through the 2‐oxo‐2,5‐dihydro‐1H‐pyrrole ring. The hydroxyl substituent at one of the newly created chiral centres, which have relative R,R stereochemistry, is trans with respect to the oxo group of the pyrrole ring in (I), synthesized using acetaldehyde. When a larger aldehyde was used, as in compounds (II) and (III), the hydroxyl substituent was found to be cis with respect to the oxo group of the pyrrole ring. Here, the relative stereochemistry of the newly created chiral centres is R,S. In compound (I), O—H...O hydrogen bonding leads to an interesting hexagonal arrangement of symmetry‐related molecules. In (II) and (III), the hydroxyl groups are involved in bifurcated O—H...O hydrogen bonds, and centrosymmetric hydrogen‐bonded dimers are formed. The Mukaiyama crossed‐aldol‐type reaction was successful when using the 2‐nitrophenyl‐substituted hydroxypyrrole, or the unsubstituted hydroxypyrrole, and boron trifluoride diethyl ether as catalyst. The synthetic procedure leads to a syn configuration of the two newly created chiral centres in all three compounds.     

Catalytic,Cascade Ring‐Opening Benzannulations of 2,3‐Dihydrofuran O,O‐ and N,O‐Acetals

An Al(OTf)₃‐catalyzed intramolecular cascade ring‐opening benzannulation of 2,3‐dihydrofuran O,O‐ and N,O‐acetals is described. The cascade sequence involves the dihydrofuran ring‐opening by acetal hydrolysis, an intramolecular Prins‐type cyclization, and aromatization to generate an array of benzo‐fused (hetero)aromatic systems in up to 95 % yield. This method represents the first example of dihydrofuran acetal usage in benzannulation reactions. The approach provides excellent regiocontrol based on the choice of alkenes used to form the requisite dihydrofuran acetals.     

Stereochemical assignment of five new lignan glycosides from Viscum album by NMR study combined with CD spectroscopy

The chemical study of the leaves and twigs of Viscum album led to the isolation of five new lignan glycosides, namely, ligalbumosides A–E (2‐6) and one known lignan glycoside, alangilignoside C (1). The structures of five new lignan glycosides were determined to be (7R,8S,8'S)‐4,9,4'‐trihydroxy‐3,5,3',5'‐tetramethoxy‐7,9'‐epoxylignan 9‐O‐β‐D‐glucopyranoside (2), (7S,8S,7'S,8'R)‐4,9,4'‐trihydroxy‐3,5,3',5',7'‐pentamethoxy‐7,9'‐epoxylignan 9‐O‐β‐D‐glucopyranoside (3), (7R,8R,7'S,8'S)‐4,9,4'‐trihydroxy‐3,5,3',5',7'‐pentamethoxy‐7,9'‐epoxylignan 9‐O‐β‐D‐glucopyranoside (4), (7S,8R,7'S,8'R)‐4,9,4'‐trihydroxy‐3,5,3',5',7'‐pentamethoxy‐7,9'‐epoxylignan 9‐O‐β‐D‐glucopyranoside (5), and (7R,8S,7'R,8'S)‐4,9,4',7'‐tetrahydroxy‐3,5,3',5'‐tetramethoxy‐7,9'‐epoxylignan 9‐O‐β‐D‐glucopyranoside (6) using 1D‐, 2D‐NMR, and CD spectra, chemical methods, as well as comparing the results with those reported in the literature. Copyright © 2012 John Wiley & Sons, Ltd.     

Preparation and structural analysis of (±)‐cis‐ethyl 2‐sulfanylidenedecahydro‐1,6‐naphthyridine‐6‐carboxylate and (±)‐trans‐ethyl 2‐oxooctahydro‐1H‐pyrrolo[3,2‐c]pyridine‐5‐carboxylate

Bicycle ring closure on a mixture of (4aS,8aR)‐ and (4aR,8aS)‐ethyl 2‐oxodecahydro‐1,6‐naphthyridine‐6‐carboxylate, followed by conversion of the separated cis and trans isomers to the corresponding thioamide derivatives, gave (4aSR,8aRS)‐ethyl 2‐sulfanylidenedecahydro‐1,6‐naphthyridine‐6‐carboxylate, C₁₁H₁₈N₂O₂S. Structural analysis of this thioamide revealed a structure with two crystallographically independent conformers per asymmetric unit (Z′ = 2). The reciprocal bicycle ring closure on (3aRS,7aRS)‐ethyl 2‐oxooctahydro‐1H‐pyrrolo[3,2‐c]pyridine‐5‐carboxylate, C₁₀H₁₆N₂O₃, was also accomplished in good overall yield. Here the five‐membered ring is disordered over two positions, so that both enantiomers are represented in the asymmetric unit. The compounds act as key intermediates towards the synthesis of potential new polycyclic medicinal chemical structures.     

Synthesis,pH‐ and temperature‐induced micellization and gelation of doubly hydrophilic triblock copolymer of poly(N,N‐dimethylamino‐2‐ethylmethacrylate)‐b‐poly(ethylene glycol)‐b‐poly(N,N‐dimethylamino‐2‐ethylmethacrylate) in aqueous solutions

A doubly hydrophilic triblock copolymer of poly(N,N‐dimethylamino‐2‐ethyl methacrylate)‐b‐Poly(ethylene glycol)‐b‐poly(N,N‐dimethylamino‐2‐ethylmethacrylate) (PDMAEMA‐b‐PEG‐b‐PDMAEMA) with well‐defined structure and narrow molecular weight distribution (M_w/M_n = 1.21) was synthesized in aqueous medium via atom transfer radical polymerization (ATRP) of N,N‐dimethylamino‐2‐ethylmethacrylate (DMAEMA) initiated by the PEG macroinitiator. The macroinitiator and triblock copolymer were characterized with ¹H NMR and gel permeation chromatography (GPC). Fluorescence spectroscopy, dynamic light scattering (DSL), transmittance measurement, and rheological characterization were applied to investigate pH‐ and temperature‐induced micellization in the dilute solution of 1 mg/mL when pH > 13 and gelation in the concentrated solution of 25 wt % at pH = 14 and temperatures beyond 80 °C. The unimer of R_h = 3.7 ± 0.8 nm coexisted with micelle of R_h = 45.6 ± 6.5 nm at pH 14. Phase separation occurred in dilute aqueous solution of the triblock copolymer of 1 mg/mL at about 50 °C. Large aggregates with R_h = 300–450 nm were formed after phase separation, which became even larger as R_h = 750–1000 nm with increasing temperature. The gelation temperature determined by rheology measurement was about 80 °C at pH 14 for the 25 wt % aqueous solution of the triblock copolymer. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5869–5878, 2008     

Asymmetric Tandem 1,5‐Hydride Shift/Ring Closure for the Synthesis of Chiral Spirooxindole Tetrahydroquinolines

The direct functionalization of sp³ C?H bonds through a tandem 1,5‐hydride shift/ring closure is described. Various optically active spirooxindole tetrahydroquinoline derivatives bearing contiguous quaternary or tertiary stereogenic carbon centers were readily synthesized. A chiral scandium complex of N,N′‐dioxide promoted the reactions in good yields (up to 97 %) with excellent diastereoselectivities (>20:1) and enantioselectivities (up to 94 % ee). Kinetic isotope effect (KIE) experiments and internal redox reactions of chiral substrates were conducted, and the results provided intriguing information that helped clarify the mechanism of the reaction.     

Cucurbitane‐type triterpene glycosides from the fruits of Momordica charantia

The chemical study of Momordica charantia fruits led to the isolation of three new cucurbitane triterpene glycosides, momordicosides U, V, and W (1–3). The structures of these compounds were determined to be (19R, 23R)‐5β, 19‐epoxy‐19‐methoxycucurbita‐6,24‐diene‐3β, 23‐diol 3‐O‐β‐D‐allopyranoside (1), (23R)‐5β, 19‐epoxycucurbita‐6,24‐diene‐3β, 23‐diol 3‐O‐β‐D‐allopyranoside (2), and (19R)‐5β, 19‐epoxy‐19,25‐dihydroxycucurbita‐6,23(E)‐diene‐3β‐ol 3‐O‐β‐D‐glucopyranoside (3), by chemical and spectroscopic methods. Copyright © 2010 John Wiley & Sons, Ltd.     

Four New Lignan Glycosides from Osmanthus fragrans Lour. var. aurantiacus Makino

Four new tetrahydrofuranoid lignan glycosides, (7S,8R,7′R,8′S)‐4,9,4′,7′‐tetrahydroxy‐3,3′‐dimethoxy‐7,9′‐epoxylignan 9‐O‐β‐D ‐glucopyranoside ( 2 ), (7R,8S,7′S,8′R)‐4,9,4′,7′‐tetrahydroxy‐3,3′‐dimethoxy‐7,9′‐epoxylignan 9‐O‐β‐D ‐glucopyranoside ( 3 ), (7R,8S,7′R,8′S)‐4,9,4′,9′‐tetrahydroxy‐3,3′‐dimethoxy‐7,7′‐epoxylignan 9‐O‐β‐D ‐glucopyranoside ( 4 ), and rel‐(7R,8S,7′S,8′R)‐4,9,4′,9′‐tetrahydroxy‐3,3′‐dimethoxy‐7,7′‐epoxylignan 9‐O‐β‐D ‐glucopyranoside ( 5 ), and ten known lignan glycosides, 1 and 6 – 14 , were isolated from the leaves of Osmanthus fragrans Lour. var. aurantiacus Makino . Their structures were established on the basis of spectral and chemical studies.     

N—H⋯N and C—H⋯π inter­actions in 4‐amino‐3‐methyl‐5‐(p‐tol­yl)‐4H‐1,2,4‐triazole and 4‐amino‐3‐methyl‐5‐phenyl‐4H‐1,2,4‐triazole

The title compounds, C₁₀H₁₂N₄, (I), and C₉H₁₀N₄, (II), have been synthesized and characterized both spectroscopically and structurally. The dihedral angles between the triazole and benzene ring planes are 26.59 (9) and 42.34 (2)°, respectively. In (I), mol­ecules are linked principally by N—H⋯N hydrogen bonds involving the amino NH₂ group and a triazole N atom, forming R₄⁴(20) and R₂⁴(10) rings which link to give a three‐dimensional network of mol­ecules. The hydrogen bonding is supported by two different C—H⋯π inter­actions from the tolyl ring to either a triazole ring or a tolyl ring in neighboring mol­ecules. In (II), inter­molecular hydrogen bonds and C—H⋯π inter­actions produce R₃⁴(15) and R₄⁴(21) rings.