Concise and facile synthesis of (R,R)-dexmethylphenidate hydrochloride and its three stereoisomers

A new and concise route is reported for the first time for the preparation of four stereoisomers of dexmethylphenidate hydrochloride starting from a single reactant, 2-benzyolpyridine, through an eight-step reaction process, which includes hydrogenation, protection, oxidation, chiral separation, Wittig reaction, hydroboration, pyridinium dichromate oxidation, and methyl esterification. The absolute configuration of the two chiral centers of each stereoisomer was confirmed by X-ray and chiral HPLC analyses.     

3β,17-二羟基-16-氨基-5α-雄甾烷四个立体异构体的合成

以表雄酮(1)为原料,由中间体3β-羟基-5α-雄甾-16-烯(3)合成3β,17α-二羟基-16α-氨基-5α-雄甾烷(7)和它的16β-氨基异构体(10a);由中间体3β-羟基-16α-溴-5α-雄甾-17-酮(12)合成3β,17β-二羟基-16α-氨基-5α-雄甾烷(21)和它的16β-氨基异构体(15)。上述四个立体异构体均通过化学转化以及波测试谱确证了其构型。     

The Complexation of Some Amino Acids by Isomers of Dicyclohexano-18-Crown-6 and 18-Crown-6 in Methanol

The complexation of some amino acids (glycine, L-alanine,L-leucine, L-valine, and L-serine) by the cis-syn-cisand cis-anti-cis isomers of dicyclohexano-18-crown-6 (DC18C6) in methanol was studied by calorimetric titrationmeasurements. Both isomers exhibited a significant ability to bind the amino acidsmentioned above. The results obtained demonstrate that the structural isomers ofDC18C6 are significantly different in terms of thermodynamics concerning their complexationwith the amino acids. The stability constants and the thermodynamic data forthe reaction of the amino acids under study in protonated form and 18-crown-6 (18C6) are reported.     

Synthesis of Highly Luminescent Tris-Fluorenyl Chromophores as Intermediates of Potential Nonlinear Photonic Materials

In our effort to enhance the cross section of simultaneous multiphoton absorption of C₆₀-based photonic nanomaterials, a novel highly luminescent tris-fluorenyl ring-interconnected chromophore tris-DPAF-C₉ was designed and synthesized using a C ₃ symmetrical triaminobenzene core as the synthon. The structural moiety bears a close resemblance to that of 2-diphenylamino-9,9-dialkylfluorenyl attachment in the previously studied C₆₀(> DPAF-C_n)_x. The product tris-DPAF-C₉ was fully characterized by NMR, UV, IR, and MALDI-TOF MS spectroscopic methods. Based on the molecular energy calculation at MOPAC PM3 level, it suggested the presence of two possible cis/trans stereoisomers on the configuration of fluorenyl moieties. Consequently, a lower heat formation (ΔH _f) of 19.9 kcal/mol was found for the tris-cis C₉-isomer as the favorable one vs 47.9 kcal/mol for the bis-mono-trans C₉-isomer.     

A reactive and environmentally friendly protocol for expeditious synthesis of various resorcinarenes using zinc hydrogen sulfate

In this work, for the first time, metal hydrogen phosphates and sulfates have been studied as effective solid acid catalysts for the condensation of resorcinol with aromatic and aliphatic aldehydes to give tetrameric cyclic products, resorcinarenes, which have major roles in biological and industrial activities. This catalyst has several advantages, it is non-toxic, thermally and mechanically stable, inexpensive and highly resistant against organic solvents. It increases the reaction rate about six fold and makes this method an attractive alternative to the existing methods for resorcinarene formation. Interestingly, the present catalyst exhibited a high turnover number (TON) and turnover frequency (TOF) which were even comparable with that of HCl.     

Synthesis of Novel N-Acylhydrazones and Their C-N/N-N Bond Conformational Characterization by NMR Spectroscopy

In this article, a synthesis of N’-(benzylidene)-2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetohydrazides and their structural interpretation by NMR experiments is described in an attempt to explain the duplication of some peaks in their ¹H- and ¹³C-NMR spectra. Twenty new 6-methyl-1H-pyrazolo[3,4-b]quinoline substituted N-acylhydrazones 6(a–t) were synthesized from 2-chloro-6-methylquinoline-3-carbaldehyde (1) in four steps. 2-Chloro-6-methylquinoline-3-carbaldehyde (1) afforded 6-methyl-1H-pyrazolo[3,4-b]quinoline (2), which upon N-alkylation yielded 2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetate (3). The hydrazinolysis of 3 followed by the condensation of resulting 2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetohydrazide (4) with aromatic aldehydes gave N-acylhydrazones 6(a–t). Structures of the synthesized compounds were established by readily available techniques such as FT-IR, NMR and mass spectral studies. The stereochemical behavior of 6(a–t) was studied in dimethyl sulfoxide-d₆ solvent by means of ¹H NMR and ¹³C NMR techniques at room temperature. NMR spectra revealed the presence of N’-(benzylidene)-2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetohydrazides as a mixture of two conformers, i.e., E_(C=N)(N-N) synperiplanar and E_(C=N)(N-N) antiperiplanar at room temperature in DMSO-d₆. The ratio of both conformers was also calculated and E_{(C=N) (N-N)} syn-periplanar conformer was established to be in higher percentage in equilibrium with the E_{(C=N) (N-N)} anti-periplanar form.     

Stereoisomer separation of flavanones and flavanone‐7‐O‐glycosides by means of nanoliquid chromatography employing derivatized β‐cyclodextrins as mobile‐phase additive

A nanoliquid chromatographic method for the stereoisomer separation of some flavanone aglycones and 7‐O‐glycosides has been proposed employing a C18 capillary column and a chiral mobile‐phase additive such as cyclodextrin. The chiral separation of eriodictyol, naringenin, and hesperitin was obtained by addition of carboxymethyl‐β‐cyclodextrin to the mobile phase, whereas eriocitrin, naringin, narirutin, and hesperidin diastereoisomers were resolved by using sulfobutyl ether‐β‐cyclodextrin. The influence of the composition of the mobile phase, the length of the capillary column, and the flow rate on the chiral recognition were investigated. At optimum conditions, baseline separation for the selected aglycones and glycosylated forms were achieved with a mobile phase consisting of 50 mM sodium acetate buffer pH 3 and 30% methanol containing 20 mM of carboxymethyl‐β‐cyclodextrin and 10 mM of sulfobutyl ether‐β‐cyclodextrin, respectively. Precision, linearity, and sensitivity of the method were tested. Limits of detection and quantification for the studied flavanone glycosides were in the range 1.3‐2.5 and 7.5‐12.5 µg/mL, respectively. The method was used for the determination of the diastereomeric composition of the flavanone‐7‐O‐glycosides in Citrus juices after solid‐phase extraction procedure.     

Understanding the chiral recognitions between neuraminidases and inhibitors: Studies with DFT,docking, and MD methods

The chiral recognitions between various neuraminidases (NA) and 5‐[(1R,2S)‐1‐(acetylamino)‐2‐ methoxy‐2‐methylpentyl]‐4‐[(1Z)‐1‐propenyl)‐(4S,5R)]‐D‐proline (BL) stereoisomers have been theoretically studied. The zwitterions of BL are responsible for the bioactivities, and electrostatic rather than van der Waals (vdW) contributions play a significant role. With the presence of NA proteins, the orders of relative stabilities of the BL stereoisomers are greatly altered; meanwhile, the ranges are significantly enlarged, ensuring the respective recognitions of the BL9z, BL3z, BL2z, and BL1z stereoisomers by the N1, N2, N9 subtype, and B type NA proteins. It is mainly due to geometric complementarities of the NA active sites with the BL carboxyl and propenyl groups. The recognitions of proteins with chiral ligands are rather targeted, even applicable to N2 and N9 with high structural similarities. Thus, the significance of chirality is addressed for the designs of anti‐influenza drugs, which aids our understanding of chiral recognitions between proteins and ligands. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Graphs to chemical structures 3. General theorems with the use of different sets of sphericity indices for combinatorial enumeration of nonrigid stereoisomers

The extended sphericity indices of k-cycles, which were defined in Part 2 of this series (S. Fujita, Theor Chem Acc, Online: http://www.springerlink.com/index/10.1007/s00214-004-0606-z) according to the enantiospheric, homospheric, or hemispheric nature of each k-cycle, are further extended to prove more general theorems for enumerating nonrigid stereoisomers with rotatable ligands. One of the extended points is the use of different sets of sphericity indices to treat one or more orbits contained in skeletons and ligands. Another is to take account of chirality in proligands and sub-proligands, the latter of which are introduced to consider further inner structures of ligands. Two theorems for enumerating nonrigid stereoisomers are proved by adopting two schemes of their derivation, i.e., the scheme ``positions of a skeleton ⇐ proligands ⇐ ligands (positions of a ligand ⇐ sub-proligands)' and the scheme ``(positions of a skeleton ⇐ proligands ⇐ ligands (positions of a ligand)) ⇐ sub-proligands'. The theorems are applied to the stereoisomerism of trihydroxyglutaric acids. Thereby, it is demonstrated where Pólya's theorem and other previous methods are deficient, when applied to the enumeration of stereoisomers.