Enantioselective anion exchangers based on cinchona alkaloid‐derived carbamates: Influence of C8/C9 stereochemistry on chiral recognition

Four diastereomeric chiral stationary phases (CSPs) based on quinine, quinidine, epiquinine, and epiquinidine tert‐butyl carbamate selectors were synthesized and evaluated under ion exchange HPLC conditions with a set of racemic N‐acylated and N‐oxycarbonylated α‐amino acids as selectands. The enantioseparation potential of quinine‐ and quinidine‐derived CSPs proved to be far superior to that of their C₉‐epimeric congeners. The absolute configuration of C₉ stereogenic center of the cinchonan backbone of these selectors was identified as the structural feature controlling the elution order. Guided by an X‐ray structure of a most favorable selector–selectand complex and the observed chromatographic enantioseparation data, a chiral recognition model was advanced. The contributions of ion‐pairing, π–π donor–acceptor, hydrogen bonding and steric interactions were established as crucial factors. Chirality 11:522–528, 1999. © 1999 Wiley‐Liss, Inc.     

Development of Chiral Building Blocks Having a Bicyclo[3.3.0]Octane Framework Using a Diastereomeric Resolution‐Selective Deprotection

A protocol is presented for an efficient and practical approach to the synthesis of enantiomerically pure bicyclo[3.3.0]octane derivatives from achiral C_s‐symmetric bicyclo[3.3.0]octane‐2,8‐dione using a diastereomeric resolution‐selective deprotection method. This method affords chiral building blocks having bicyclo[3.3.0]octane framework with the same site of diastereotopic carbonyl functional group. Chirality 27:364–369, 2015. © 2015 Wiley Periodicals, Inc.     

LiTFSI‐Free Spiro‐OMeTAD‐Based Perovskite Solar Cells with Power Conversion Efficiencies Exceeding 19%

To date, the most efficient perovskite solar cells (PSCs) employ an n–i–p device architecture that uses a 2,2′,7,7′‐tetrakis(N,N‐di‐p‐methoxyphenyl‐amine)‐9,9′‐spirobifluorene (spiro‐OMeTAD) hole‐transporting material (HTM), which achieves optimum conductivity with the addition of lithium bis(trifluoromethane)sulfonimide (LiTFSI) and air exposure. However, this additive along with its oxidation process leads to poor reproducibility and is detrimental to stability. Herein, a dicationic salt spiro‐OMeTAD(TFSI)₂, is employed as an effective p‐dopant to achieve power conversion efficiencies of 19.3% and 18.3% (apertures of 0.16 and 1.00 cm²) with excellent reproducibility in the absence of LiTFSI and air exposure. As far as it is known, these are the highest‐performing n–i–p PSCs without LiTFSI or air exposure. Comprehensive analysis demonstrates that precise control of the proportion of [spiro‐OMeTAD]⁺ directly provides high conductivity in HTM films with low series resistance, fast hole extraction, and lower interfacial charge recombination. Moreover, the spiro‐OMeTAD(TFSI)₂‐doped devices show improved stability, benefitting from well‐retained HTM morphology without forming aggregates or voids when tested under an ambient atmosphere. A facile approach is presented to fabricate highly efficient PSCs by replacing LiTFSI with spiro‐OMeTAD(TFSI)₂. Furthermore, this study provides an insight into the relationship between device performance and the HTM doping level.     

Enantiomeric separation of N‐protected amino acids by non‐aqueous capillary electrophoresis using quinine or Tert‐butyl carbamoylated quinine as chiral additive

A capillary electrophoretic (CE) method for the enantioseparation of N‐protected chiral amino acids was developed using quinine and tert‐butyl carbamoylated quinine as chiral selectors added to nonaqueous electrolyte solutions (NACE). A series of various N‐derivatized amino acids were tested as chiral selectands, and in order to optimize the CE enantioseparation of these compounds, different parameters were investigated: the nature of the organic solvent, the combination of different solvents, the nature and the concentration of the background electrolyte, the selector concentration, the capillary temperature, and the applied voltage. The influence of these factors on the separation of the analyte enantiomers and the electroosmotic flow was studied. Generally, with tert‐butyl carbamoylated quinine as chiral selector, better enantioseparations were achieved than with unmodified quinine. Optimum experimental conditions were found with a buffer made of 12.5 mM ammonia, 100 mM octanoic acid, and 10 mM tert‐butyl carbamoylated quinine in an ethanol–methanol mixture (60:40 v/v). Under these conditions, DNB‐Leu enantiomers could be separated with a selectivity factor (α) of 1.572 and a resolution (Rs) of 64.3; a plate number (N) of 127,000 and an asymmetry factor (As) of 0.93 were obtained for the first migrating enantiomer. Chirality 11:622–630, 1999. © 1999 Wiley‐Liss, Inc.     

Enantioselectivity in the metabolism of mexiletine by conjugation in female patients with the arrhythmic form of chronic Chagas' heart disease

The phenomenon of enantioselectivity in the metabolism of mexiletine (MEX) conjugation was investigated in eight female patients with the arrhythmic form of chronic Chagas' heart disease treated with racemic mexiletine hydrochloride (two 100 mg capsules every 8 hr). Blood samples were collected up to 24 hr after the administration of the morning dose, with discontinuation of the subsequent doses during the study period. Plasma concentrations of N‐hydroxymexiletine glucuronide were calculated as the difference between the concentrations of unchanged and total (unchanged + conjugated) MEX enantiomers. Total plasma MEX concentrations were analyzed by HPLC after enzymatic hydrolysis with β‐glucuronidase, the formation of diastereomeric derivatives with the chiral reagent N‐acetyl‐l ‐cysteine/o‐phthalaldehyde, and fluorescence detection. The differences in the pharmacokinetic parameters of the enantiomers were evaluated by the paired t‐test. The plasma concentrations of the (+)‐(S)‐MEX did not differ before and after enzymatic hydrolysis. The pharmacokinetic parameters calculated for (−)‐(R)‐N‐hydroxymexiletine glucuronide are presented as means (95% confidence interval): maximum plasma concentration C_max = 194.0 ng · ml⁻¹ (154.3–233.7), time to maximum plasma concentration t_max = 1.4 hr (0.3–2.5), area under the plasma concentration versus time curve AUC^0–24 = 2099.2 ng · h · ml⁻¹ (1585.6–2612.6), elimination half‐life t_1/2β = 12.8 hr (9.9–15.6) and extent of conjugation of 31.6% (24.3–38.9%). The present data indicate stereospecific conjugation of (−)‐(R)‐N‐hydroxymexiletine in the female patients with the arrhythmic form of Chagas' heart disease. Chirality 11:29–32, 1999. © 1999 Wiley‐Liss, Inc.     

Synthesis and discovery of potent carbonic anhydrase,acetylcholinesterase, butyrylcholinesterase,and α‐glycosidase enzymes inhibitors: The novel N,N′‐bis‐cyanomethylamine and alkoxymethylamine derivatives

During this investigation, N,N′‐bis‐azidomethylamines, N,N′‐bis‐cyanomethylamine, new alkoxymethylamine and chiral derivatives, which are considered to be a new generation of multifunctional compounds, were synthesized, functional properties were investigated, and anticholinergic and antidiabetic properties of those compounds were studied through the laboratory tests, and it was approved that they contain physiologically active compounds rather than analogues. Novel N‐bis‐cyanomethylamine and alkoxymethylamine derivatives were effective inhibitors of the α‐glycosidase, cytosolic carbonic anhydrase I and II isoforms, butyrylcholinesterase (BChE), and acetylcholinesterase (AChE) with K_i values in the range of 0.15–13.31 nM for α‐glycosidase, 2.77–15.30 nM for human carbonic anhydrase isoenzymes I (hCA I), 3.12–21.90 nM for human carbonic anhydrase isoenzymes II (hCA II), 23.33–73.23 nM for AChE, and 3.84–48.41 nM for BChE, respectively. Indeed, the inhibition of these metabolic enzymes has been considered as a promising factor for pharmacologic intervention in a diversity of disturbances.     

A Strategy for Synthesis of Carbon Nitride Induced Chemically Doped 2D MXene for High‐Performance Supercapacitor Electrodes

A step‐by‐step strategy is reported for improving capacitance of supercapacitor electrodes by synthesizing nitrogen‐doped 2D Ti₂CT_x induced by polymeric carbon nitride (p‐C₃N₄), which simultaneously acts as a nitrogen source and intercalant. The NH₂CN (cyanamide) can form p‐C₃N₄ on the surface of Ti₂CT_x nanosheets by a condensation reaction at 500–700 °C. The p‐C₃N₄ and Ti₂CT_x complexes are then heat‐treated to obtain nitrogen‐doped Ti₂CT_x nanosheets. The triazine‐based p‐C₃N₄ decomposes above 700 °C; thus, the nitrogen species can be surely doped into the internal carbon layer and/or defect site of Ti₂CT_x nanosheets at 900 °C. The extended interlayer distance and c‐lattice parameters (c‐LPs of 28.66 Å) of Ti₂CT_x prove that the p‐C₃N₄ grown between layers delaminate the nanosheets of Ti₂CT_x during the doping process. Moreover, 15.48% nitrogen doping in Ti₂CT_x improves the electrochemical performance and energy storage ability. Due to the synergetic effect of delaminated structures and heteroatom compositions, N‐doped Ti₂CT_x shows excellent characteristics as an electrochemical capacitor electrode, such as perfectly rectangular cyclic voltammetry results (CVs, R² = 0.9999), high capacitance (327 F g^?1 at 1 A g^?1, increased by ≈140% over pristine‐Ti₂CT_x), and stable long cyclic performance (96.2% capacitance retention after 5000 cycles) at high current density (5 A g^?1).     

First Synthesis of Double Headed 1,3,4‐Oxadiazino[6,5‐b]indole Acyclo C‐Nucleosides

Condensation of 1,3‐dihydro‐2,3‐dioxo‐2H‐indoles (1a–c) with galactaric acid bis hydrazide (2) gave the corresponding galactaric acid bis[2‐(1,2‐dihydro‐2‐oxo‐3H‐indol‐3‐ylidene)hydrazides] (3a–c). Acetylation of the latter compounds with acetic anhydride in the presence of pyridine at ambient temperature gave the 2,3,4,5‐tetra‐O‐acetylgalactaric acid bis[2‐(1,2‐dihydro‐2‐oxo‐1‐substituted‐3H‐indol‐3‐ylidene)hydrazides] (4b–d). Heterocyclization of the tetra‐O‐acetates 4b–d by heating with thionyl chloride afforded the double headed acyclo C‐nucleosides: 1,2,3,4‐tetra‐O‐acetyl‐1,4‐bis{9‐substituted‐1,3,4‐oxadiazino[6,5‐b]indol‐2‐yl‐1‐ium}‐galacto‐tetritol dichlorides (5b–d). Structures of the prepared compounds were elucidated from their spectral properties.     

Catalytic and Dual‐Conductive Matrix Regulating the Kinetic Behaviors of Polysulfides in Flexible Li–S Batteries

The main challenge in developing foldable Li–S batteries (LSB) lies in developing an electrode that is ultraflexible, conductive, and catalytic for dissolved lithium polysulfides (LiPSs). In this paper, lightweight macromolecule graphitic carbon nitride (g‐C₃N₄) film and a conductive polymer (CP) of poly(3,4‐ethylenedioxythiophene) shell are introduced into flexible LSBs by compositing with carbon cloth (CC). In the designed hybrid of CP/g‐C₃N₄@CC, 2D g‐C₃N₄ is used in the form of an effective trapper and functions as a continuous catalytic layer for LiPSs via the formation of pyridinic‐N‐Li bonds. This is revealed by both experimental investigations and theoretical analysis. The sandwich‐like CC and CP simultaneously bring an omnidirectional conductive network for fast interfacial reaction kinetics. With these benefits, the self‐supported CP/g‐C₃N₄@CC forms a powerful interaction system to fully in situ “lock” LiPSs in the commercial CC matrix. Thus, a substantially enhanced electrochemical performance is obtained at a high sulfur loading (4.7 mg cm^–2) even operating in a pouch cell. This work may provide a potential avenue for practical use of high‐performance LSBs toward flexible energy‐storage devices.     

Atomic Layer Deposition of Tin Monosulfide Thin Films

Thin film solar cells made from earth‐abundant, non‐toxic materials are needed to replace the current technology that uses Cu(In,Ga)(S,Se)₂ and CdTe, which contain scarce and toxic elements. One promising candidate absorber material is tin monosulfide (SnS). In this report, pure, stoichiometric, single‐phase SnS films were obtained by atomic layer deposition (ALD) using the reaction of bis(N,N′‐diisopropylacetamidinato)tin(II) [Sn(MeC(N‐ⁱPr)₂)₂] and hydrogen sulfide (H₂S) at low temperatures (100 to 200 °C). The direct optical band gap of SnS is around 1.3 eV and strong optical absorption (α > 10⁴ cm^?1) is observed throughout the visible and near‐infrared spectral regions. The films are p‐type semiconductors with carrier concentration on the order of 10¹⁶ cm^?3 and hole mobility 0.82–15.3 cm²V^?1s^?1 in the plane of the films. The electrical properties are anisotropic, with three times higher mobility in the direction through the film, compared to the in‐plane direction.     

Bromolactamization: Key Step in the Stereoselective Synthesis of Enantiomerically Pure,cis‐Configured Perhydropyrroloquinoxalines

Compounds based on the pyrroloquinoxaline system can interact with serotonin 5‐HT₃, cannabinoid CB₁, and μ‐opioid receptors. Herein, a chiral pool synthesis of diastereomerically and enantiomerically pure bromolactam (S,R,R,R)‐ 14A is presented. Introduction of the cyclohexenyl ring at the N‐atom of (S)‐proline derivatives 8 or methyl (S)‐pyroglutamate ( 12 ) led to the N‐cyclohexenyl substituted pyrrolidine derivatives 4 and 13 , respectively. All attempts to cyclize the (S)‐proline derivatives 4 with a basic pyrrolidine N‐atom via [3 + 2] cycloaddition, aziridination, or bromolactamization failed. Fast aromatization occurred during treatment of cyclohexenamines under halolactamization conditions. In contrast, reaction of a 1:1 mixture of diastereomeric pyroglutamates (S,R)‐ 13bA and (S,S)‐ 13bB with LiO^tBu and NBS provided the tricyclic bromolactam (S,R,R,R)‐ 14A with high diastereoselectivity from (S,R)‐ 13bA , but did not transform the diastereomer (S,S)‐ 13bB . The different behavior of the diastereomeric pyroglutamates (S,R)‐ 13bA and (S,S)‐ 13bB is explained by different energetically favored conformations. Chirality 26:793–800, 2014. © 2014 Wiley Periodicals, Inc.     

Photoactive Blend Morphology Engineering through Systematically Tuning Aggregation in All‐Polymer Solar Cells

Polymer aggregation plays a critical role in the miscibility of materials and the performance of all‐polymer solar cells (APSCs). However, many aspects of how polymer texturing and aggregation affect photoactive blend film microstructure and photovoltaic performance are poorly understood. Here the effects of aggregation in donor–acceptor blends are studied, in which the number‐average molecular weights (M_ns) of both an amorphous donor polymer, poly[4,8‐bis(5‐(2‐ethylhexyl)thiophen‐2‐yl)benzo[1,2‐b;4,5‐b′]dithiophene‐2,6‐diyl‐alt‐(4‐(2‐ethylhexyl)‐3‐fluorothieno[3,4‐b]thiophene‐)‐2‐carboxylate‐2‐6‐diyl)] ( PBDTT‐FTTE ) and a semicrystalline acceptor polymer, poly{[N,N′‐bis(2‐octyldodecyl)naphthalene‐1,4,5,8‐bis(dicarboximide)‐2,6‐diyl]‐alt‐5,5′‐(2,2′‐bithiophene)} ( P(NDI2OD‐T2) ) are systematically varied. The photovoltaic performance is correlated with active layer microstructural and optoelectronic data acquired by in‐depth transmission electron microscopy, grazing incidence wide‐angle X‐ray scattering, thermal analysis, and optical spectroscopic measurements. Coarse‐grained modeling provides insight into the effects of polymer aggregation on the blend morphology. Notably, the computed average distance between the donor and the acceptor polymers correlates well with solar cell photovoltaic metrics such as short‐circuit current density (J_sc) and represents a useful index for understanding/predicting active layer blend material intermixing trends. Importantly, these results demonstrate that for polymers with different texturing tendencies (amorphous/semicrystalline), the key for optimal APSC performance, photovoltaic blend morphology can be controlled via both donor and acceptor polymer aggregation.     

Effect of Aglycon Structure on Saccharide Elongation by Cells

Alkyl N‐acetyl‐β‐D ‐glucosaminide (GlcNAc primers) with different aglycon moieties were synthesized and used to determine the effect of the aglycon structure on cellular saccharide elongation. Dodecyl N‐acetyl‐β‐D ‐glucosaminide (GlcNAc‐C12), tridecan‐7‐yl N‐acetyl‐β‐D ‐glucosaminide (GlcNAc‐2C6), and pentacosan‐13‐yl N‐acetyl‐β‐D ‐glucosaminide (GlcNAc‐2C12) primers were synthesized by glycosylation of dodecan‐1‐ol, tridecan‐7‐ol, and pentacosan‐13‐ol, respectively, with peracetylglucosamine. These primers were introduced to mouse B16 melanoma cells to prepare glycolipids. After 48 h incubation, results showed that GlcNAc‐C12 was elongated to give NeuAc‐Gal‐GlcNAc‐C12. GlcNAc‐2C6 was also elongated to afford Gal‐GlcNAc‐2C6 and NeuAc‐Gal‐GlcNAc‐2C6. On the other hand, GlcNAc‐2C12 primer was not elongated. Significantly, the results demonstrated that the amount of glycosylated product increased 1.5‐times by modifying the aglycon structure of GlcNAc from C₁₂ to 2 C₆ despite having almost the same number of C‐units.     

Luminescent properties of a novel fluorene organic material

The photo‐physical properties of 6,6′‐(9H‐fluoren‐9,9‐diyl)bis(2,3‐bis(9,9‐dihexyl‐9H‐fluoren‐2‐yl)quinoxaline) (BFLBBFLYQ) and its blend doped with N′‐biphenyl‐N,N′‐bis‐(3‐methylphenyl)‐1,1′‐biphenyl‐4,4′‐diamine (TPD) were investigated. The absorption, photoluminescence (PL) and electroluminescence (EL) properties of pristine BFLBBFLYQ and blend in solution and spin‐coated film are outlined, including a discussion of charge‐transfer (CT) exciplex emission of BFLBBFLYQ:TPD blend in the solid state. The luminescent properties of BFLBBFLYQ films using different deposition processes were studied. It was found that the low‐energy emission bands at 530–570 nm appeared in the PL spectra of BFLBBFLYQ evaporated films in ultra‐high vacuum. Also, the low‐energy band was the exclusive emission in the EL spectra of BFLBBFLYQ films. Copyright © 2008 John Wiley & Sons, Ltd.     

Toward engineering efficient peptidomimetics. Screening conformational landscape of two modified dehydroaminoacids

Effective peptidomimetics should posses structural rigidity and appropriate interaction pattern leading to potential spatial and electronic matching to the target receptor site. Rational design of such small bioactive molecules could push chemical synthesis and molecular modeling toward faster progress in medicinal chemistry. Conformational properties of N‐t‐butoxycarbonyl‐glycine‐(E/Z)‐dehydrophenylalanine N′,N′‐dimethylamides (Boc‐Gly‐(E/Z)‐ΔPhe‐NMe₂) in chloroform were studied by NMR and IR spectroscopy. The experimental findings were supported by extensive calculations at DFT(B3LYP, M06‐2X) and MP2 levels of theory and the β‐turn tendency for both isomers of the studied dipeptide were determined in vacuum and in solution. The theoretical data and experimental IR results were used as an additional information for the NMR‐based determination of the detailed solution conformations of the peptides. The obtained results reveal that N‐methylation of C‐terminal amide group changes dramatically the conformational properties of studied dehydropeptides. Theoretical conformational analysis reveals that the tendency to adopt β‐turn conformations is much weaker for the N‐methylated Z isomer (Boc‐Gly‐(Z)‐ΔPhe‐NMe₂), both in vacuum and in polar environment. On the contrary, N‐methylated E isomer (Boc‐Gly‐(E)‐ΔPhe‐NMe₂) can easily adopt β‐turn conformation, but the backbone torsion angles (φ₁, ψ₁, φ₂, ψ₂) are off the limits for common β‐turn types. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 28–40, 2014.     

Solvent effects on the conformational preferences of model peptoids. MP2 study

The influence of aqueous environment on the main‐chain conformation (ω₀, ?, and ψ dihedral angles) of two model peptoids: N‐acetyl‐N‐methylglycine N’‐methylamide (Ac‐N(Me)‐Gly‐NHMe) ( 1 ) and N‐acetyl‐N‐methylglycine N’,N’‐dimethylamide (Ac‐N(Me)‐Gly‐NMe₂) ( 2 ) was investigated by MP2/6‐311++G(d,p) method. The Ramachandran maps of both studied molecules with cis and trans configuration of the N‐terminal amide bond in the gas phase and in water environment were obtained and all energy minima localized. The polarizable continuum model was applied to estimate the solvation effect on conformation. Energy minima of the Ac‐N(Me)‐Gly‐NHMe and Ac‐N(Me)‐Gly‐NMe₂ have been analyzed in terms of the possible hydrogen bonds and C = O dipole attraction. To validate the theoretical results obtained, conformations of the similar structures gathered in the Cambridge Crystallographic Data Centre were analyzed. Obtained results indicate that aqueous environment in model peptoids 1 and 2 favors the conformation F (? and ψ = ?70º, 180º), and additionally significantly increases the percentage of structures with cis configuration of N‐terminal amide bond in studied compounds. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.     

Synthesis of new C3 symmetric amino acid‐ and aminoalcohol‐containing chiral stationary phases and application to HPLC enantioseparations

We recently reported a new C3‐symmetric (R)‐phenylglycinol N‐1,3,5‐benzenetricarboxylic acid‐derived chiral high‐performance liquid chromatography (HPLC) stationary phase (CSP 1) that demonstrated better results as compared to a previously described N‐3,5‐dintrobenzoyl (DNB) (R)‐phenylglycinol‐derived CSP. Over a decade ago, (S)‐leucinol, (R)‐phenylglycine, and (S)‐leucine derivatives were used as the starting materials of 3,5‐DNB‐based Pirkle‐type CSPs for chiral separation. In this study, three new C3‐symmetric CSPs (CSP 2, 3, and 4) were prepared by combining the ideas and results mentioned above. Here we describe the synthetic procedures and applications of the new C3‐symmetric CSPs (CSP 2–CSP 4).     

Dominance of bacterial ammonium oxidizers and fungal denitrifiers in the complex nitrogen cycle pathways related to nitrous oxide emission

Organic compounds and mineral nitrogen (N) usually increase nitrous oxide (N₂O) emissions. Vinasse, a by‐product of bio‐ethanol production that is rich in carbon, nitrogen, and potassium, is recycled in sugarcane fields as a bio‐fertilizer. Vinasse can contribute significantly to N₂O emissions when applied with N in sugarcane plantations, a common practice. However, the biological processes involved in N₂O emissions under this management practice are unknown. This study investigated the roles of nitrification and denitrification in N₂O emissions from straw‐covered soils amended with different vinasses (CV: concentrated and V: nonconcentrated) before or at the same time as mineral fertilizers at different time points of the sugarcane cycle in two seasons. N₂O emissions were evaluated for 90 days, the period that occurs most of the N₂O emission from fertilizers; the microbial genes encoding enzymes involved in N₂O production (archaeal and bacterial amoA, fungal and bacterial nirK, and bacterial nirS and nosZ), total bacteria, and total fungi were quantified by real‐time PCR. The application of CV and V in conjunction with mineral N resulted in higher N₂O emissions than the application of N fertilizer alone. The strategy of vinasse application 30 days before mineral N reduced N₂O emissions by 65% for CV, but not for V. Independent of rainy or dry season, the microbial processes were nitrification by ammonia‐oxidizing bacteria (AOB) and archaea and denitrification by bacteria and fungi. The contributions of each process differed and depended on soil moisture, soil pH, and N sources. We concluded that amoA‐AOB was the most important gene related to N₂O emissions, which indicates that nitrification by AOB is the main microbial‐driven process linked to N₂O emissions in tropical soil. Interestingly, fungal nirK was also significantly correlated with N₂O emissions, suggesting that denitrification by fungi contributes to N₂O emission in soils receiving straw and vinasse application.     

Lewis acid catalysed methylation of N‐(9H‐fluoren‐9‐yl)methanesulfonyl (Fms) protected lipophilic α‐amino acid methyl esters

This work reports an efficient Lewis acid catalysed N‐methylation procedure of lipophilic α‐amino acid methyl esters in solution phase. The developed methodology involves the use of the reagent system AlCl₃/diazomethane as methylating agent and α‐amino acid methyl esters protected on the amino function with the (9H‐fluoren‐9‐yl)methanesulfonyl (Fms) group. The removal of Fms protecting group is achieved under the same conditions to those used for Fmoc removal. Thus the Fms group can be interchangeable with the Fmoc group in the synthesis of N‐methylated peptides using standard Fmoc‐based strategies. Finally, the absence of racemization during the methylation reaction and the removal of Fms group were demonstrated by synthesising a pair of diastereomeric dipeptides. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.