Conformationally Selective 2-Aminotetralin Ligands Targeting the alpha2A- and alpha2C-Adrenergic Receptors.

Many important physiological processes are mediated by alpha2A- and alpha2C-adrenergic receptors (α2Rs), a subtype of class A G protein-coupled receptors (GPCRs). However, α2R signaling is poorly understood, and there are few approved medications targeting these receptors. Drug discovery aimed at α2Rs is complicated by the high degree of binding pocket homology between α2AR and α2CR, which confounds ligand-mediated selective activation or inactivation of signaling associated with a particular subtype. Meanwhile, α2R signaling is complex and it is reported that activating α2AR is beneficial in many clinical contexts, while activating α2CR signaling may be detrimental to these positive effects. Here, we report on a novel 5-substituted-2-aminotetralin (5-SAT) chemotype that, depending on substitution, has diverse pharmacological activities at α2Rs. Certain lead 5-SAT analogues act as partial agonists at α2ARs, while functioning as inverse agonists at α2CRs, a novel pharmacological profile. Leads demonstrate high potency (e.g., EC50 < 2 nM) at the α2AR and α2CRs regarding Gαi-mediated inhibition of adenylyl cyclase and production of cyclic adenosine monophosphate (cAMP). To help understand the molecular basis of 5-SAT α2R multifaceted functional activity, α2AR and α2CR molecular models were built from the crystal structures and 1 µs molecular dynamics (MD) simulations and molecular docking experiments were performed for a lead 5-SAT with α2AR agonist and α2CR inverse agonist activity, i.e., (2S)-5-(2'-fluorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine (FPT), in comparison to the FDA-approved (for opioid withdrawal symptoms) α2AR/α2CR agonist lofexidine. Results reveal several interactions between FPT and α2AR and α2CR amino acids that may impact the functional activity. The computational data in conjunction with experimental in vitro affinity and function results provide information to understand ligand stabilization of functionally distinct GPCR conformations regarding α2AR and α2CRs.

Evaluation of adverse drug reactions of chemotherapeutic agents used in advanced non-small cell lung cancer - experience from a rural tertiary care institution in North Eastern India.

BACKGROUND: Lung cancer is one of the major causes of morbidity and mortality both in developed and developing countries. Adverse drug reactions (ADRs) are inevitable, albeit unwanted aspects of cancer chemotherapeutic agents used in lung cancer. AIM AND OBJECTIVES: To determine common ADRs and the severity of ADRs of different chemotherapeutic agents used in non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: The study was conducted among purposively selected 160 patients who had undergone chemotherapy for lung carcinoma. Clinical records of NSCLC patients were reviewed and data related to the socio-demographic and clinic-therapeutic profiles of patients were collected. ADRs were graded according to the Common toxicity criteria (CTC) grading. Data analysis was done using the IBM-SPSS software and presented using the principle of descriptive statistics. Relationships between ADRs and drug regimens were determined using Chi-square tests considering a 95% confidence interval and P value ≤ 0.05 as significant. RESULT: Among 160 patients, 78.8% were males and 21.3% were females. The mean age was 59.15 ± 10.6 years, illness duration was 7.5 ± 10.6 months, and treatment duration was 4.4 ± 0.91 months. The overall mortality rate and systemic toxicity of the paclitaxel-carboplatin combination were the lowest. Almost an equal proportion of moderate to severe changes in parameters such as myelosuppression, anemia, thrombocytopenia, alopecia, skin changes, allergic reaction, and peripheral neuropathy, were observed with all chemotherapeutic regimens. Gemcitabine-carboplatin regimen was associated with a higher proportion of altered liver enzymes, electrolyte imbalance, diarrhea, pleural effusion, and renal toxicities. CONCLUSION: There was a high prevalence of ADRs with different chemotherapeutic agents. Early detection of these ADRs may help in minimizing the damage by either modifying the dose or changing the offending agent.

A new class of 5-HT2A /5-HT2C receptor inverse agonists: Synthesis, molecular modeling, in vitro and in vivo pharmacology of novel 2-aminotetralins.

BACKGROUND AND PURPOSE: The 5-HT receptor subtypes 5-HT2A and 5-HT2C are important neurotherapeutic targets, though, obtaining selectivity over 5-HT2B and H1 receptors is challenging. Here, we delineated molecular determinants of selective binding to 5-HT2A and 5-HT2C receptors for novel 4-phenyl-2-dimethylaminotetralins (4-PATs). EXPERIMENTAL APPROACH: We synthesized 42 novel 4-PATs with halogen or aryl moieties at the C(4)-phenyl meta-position. Affinity, function, molecular modeling and 5-HT2A receptor mutagenesis studies were performed to understand structure-activity relationships at 5-HT2 -type and H1 receptors. Lead 4-PAT-type 5-HT2A /5-HT2C receptor inverse agonists were compared with pimavanserin, a selective 5-HT2A /5-HT2C receptor inverse agonist approved to treat Parkinson's disease-related psychosis, in the mouse head twitch response and locomotor activity assays, models relevant to antipsychotic drug development. KEY RESULTS: Most 4-PAT diastereomers in the (2S,4R)-configuration bound non-selectively to 5-HT2A , 5-HT2C and H1 receptors, with >100-fold selectivity over 5-HT2B receptors, whereas diastereomers in the (2R,4R)-configuration bound preferentially to 5-HT2A over 5-HT2C receptors and had >100-fold selectivity over 5-HT2B and H1 receptors. Results suggest that G2385.42 and V2355.39 in 5-HT2A receptors (conserved in 5-HT2C receptors) are important for high affinity binding, whereas interactions with T1945.42 and W1584.56 determine H1 receptor affinity. The 4-PAT analog (2S,4R)-4-(4'-(dimethylamino)-[1,1'-biphenyl]-3-yl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine, (2S,4R)-2k, a potent and selective 5-HT2A /5-HT2C receptor inverse agonist, had activity like pimavanserin in the mouse head twitch response assay but was distinct in not suppressing locomotor activity. CONCLUSIONS AND IMPLICATIONS: The novel 4-PAT chemotype can yield selective 5-HT2A /5-HT2C receptor inverse agonists for antipsychotic drug development by optimizing ligand-receptor interactions in transmembrane domain 5. Chirality can be exploited to attain selectivity over H1 receptors, which may circumvent sedative effects.

(S)-5-(2'-Fluorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine, a Serotonin Receptor Modulator, Possesses Anticonvulsant, Prosocial, and Anxiolytic-like Properties in an Fmr1 Knockout Mouse Model of Fragile X Syndrome and Autism Spectrum Disorder.

Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by intellectual disabilities and a plethora of neuropsychiatric symptoms. FXS is the leading monogenic cause of autism spectrum disorder (ASD), which is defined clinically by repetitive and/or restrictive patterns of behavior and social communication deficits. Epilepsy and anxiety are also common in FXS and ASD. Serotonergic neurons directly innervate and modulate the activity of neurobiological circuits altered in both disorders, providing a rationale for investigating serotonin receptors (5-HTRs) as targets for FXS and ASD drug discovery. Previously we unveiled an orally active aminotetralin, (S)-5-(2'-fluorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine (FPT), that exhibits partial agonist activity at 5-HT1ARs, 5-HT2CRs, and 5-HT7Rs and that reduces repetitive behaviors and increases social approach behavior in wild-type mice. Here we report that in an Fmr1 knockout mouse model of FXS and ASD, FPT is prophylactic for audiogenic seizures. No FPT-treated mice displayed audiogenic seizures, compared to 73% of vehicle-treated mice. FPT also exhibits anxiolytic-like effects in several assays and increases social interactions in both Fmr1 knockout and wild-type mice. Furthermore, FPT increases c-Fos expression in the basolateral amygdala, which is a preclinical effect produced by anxiolytic medications. Receptor pharmacology assays show that FPT binds competitively and possesses rapid association and dissociation kinetics at 5-HT1ARs and 5-HT7Rs, yet has slow association and rapid dissociation kinetics at 5-HT2CRs. Finally, we reassessed and report FPT's affinity and function at 5-HT1ARs, 5-HT2CRs, and 5-HT7Rs. Collectively, these observations provide mounting support for further development of FPT as a pharmacotherapy for common neuropsychiatric symptoms in FXS and ASD.

Catalytic Asymmetric Epoxidation of Aldehydes with Two VANOL-Derived Chiral Borate Catalysts.

A highly diastereo- and enantioselective method for the epoxidation of aldehydes with α-diazoacetamides has been developed with two different borate ester catalysts of VANOL. Both catalytic systems are general for aromatic, aliphatic, and acetylenic aldehydes, giving high yields and inductions for nearly all cases. One borate ester catalyst has two molecules of VANOL and the other only one VANOL. Catalysts generated from BINOL and VAPOL are ineffective catalysts. An application is shown for access to the side-chain of taxol.

Defluoridation using novel chemically treated carbonized bone meal: batch and dynamic performance with scale-up studies.

Novel defluoridating adsorbent was synthesized by chemical treatment of carbonized bone meal using aluminum sulfate and calcium oxide. Precursor for chemical treatment was prepared by partial carbonization of raw bone meal at 550 °C for 4 h. Maximum fluoride removal capacity was 150 mg/g when carbonized bone meal (100 g/L) was treated with aluminum sulfate (500 g/L) and calcium oxide (15 g/L). Morphological analysis revealed formation of a coating layer consisting of aluminum compounds on the precursor surface. This was verified by stretching frequency of aluminum hydroxide (602 cm-1) in the infrared spectra. Presence of hydroxylapatite (2θ = 30° and 2θ = 24°) and aluminum mineral phases (2θ = 44°) in the adsorbent were identified from the X-ray diffractograms. Adsorption capacity decreased from 150 mg/g (30 °C) to 120 mg/g (50 °C) indicating exothermic adsorption. Adsorption experiments under batch kinetic mode were simulated using shrinking core model. Effective fluoride diffusivity in the adsorbent and the mass transfer coefficient were estimated as 5.8 × 10-12 m2/s and 9 × 10-4 m/s, respectively. Desorption was maximum at basic pH and desorption efficiency was decreased by 31% after third cycle. Dynamic filtration with artificially fluoride-spiked solution showed that the empty bed contact time for a packed column with equal weight of carbonized and chemically treated adsorbent was 4.7 min and number of bed volumes treated (till WHO limit of 1.5 mg/L) was 340 for a column of 3-cm diameter and 18-cm length. The system was successfully tested using contaminated groundwater from an affected area. Fixed-bed column experiments were simulated from the first principles using convective pore diffusion-adsorption model for both synthetic solution and contaminated groundwater. Axial dispersion coefficient was found to be one order of magnitude less than the pore diffusivity indicating dominance of fluoride diffusion within porous network of adsorbent. The developed adsorbent exhibited antibacterial property as well.

Multicomponent Catalytic Asymmetric Synthesis of trans-Aziridines.

A multicomponent trans-aziridination of aldehydes, amines, and diazo compounds with BOROX catalysts is developed. The optimal protocol is slightly different for aryl aldehydes than for aliphatic aldehydes. The key to the success with aryl aldehydes was allowing the catalyst, aldehyde, and amine to react for 20 min before addition of the diazo compound. A variety of 11 different electron-poor and electron-rich aryl aldehydes were screened to give trans-aziridines in 73-90% yield with 82-99% ee and trans/cis selectivities of 19:1 to >99:1. The optimal protocol for the trans-aziridination of aliphatic aldehydes did not require prereaction of the catalyst, aldehyde, and amine, and instead, the diazo compound could be added directly. The scope of the reaction is limited to unbranched aliphatic aldehydes and was tolerant of a number of functional groups including ethers, esters, epoxides, carbamates, and phthalimides. A total of 10 aliphatic aldehydes were examined and found to give trans-aziridines in 60-88% yield with 60-98% ee and trans/cis selectivities of 6:1 to >99:1. Alkenyl aldehydes did not react, but an alkynyl aldehyde gave a 71% yield and 95% ee of an aziridine that was found to be the cis- and not the trans-diastereomer. The aryl and aliphatic aldehydes both gave the trans-aziridines with the same absolute configuration with the same catalyst; however, in those cases where cis-aziridines were formed, the configuration was opposite for those formed from aryl versus aliphatic aldehydes.

Investigation of antifouling and disinfection potential of chitosan coated iron oxide-PAN hollow fiber membrane using Gram-positive and Gram-negative bacteria.

Chitosan coated iron oxide nanoparticles were impregnated into polyacrylonitrile based hollow fiber membrane. The molecular weight cut off was varied in the range of 120 to 145kDa with the concentration of nanoparticles. Incorporation of nanoparticles improved the permeability, mechanical property and hydrophilicity of the membrane. The contact angle of the membrane decreased from 80° to 51° and the permeability increased by 31% at 0.5wt% nanoparticles concentration. The antibacterial and antifouling property of the membrane were investigated with two biofilm causing Gram positive and Gram negative bacteria. The damage of cell membrane was directly confirmed by release of cellular constituent absorbing in 260nm. The cellular deformation on the membrane surface was evident by direct microscopic observation in FESEM. This damage was likely caused by electrostatic interaction between NH3+ group of nanoparticles and anionic components of phosphoryl group of bacteria. The hollow fiber membrane shows promising antibiofouling property even after long experimental run as evident by 95% flux recovery ratio. The effect of operating conditions on rejection and flux profile was investigated during long experimental run. The result indicated that there was no detectable iron in the permeate sample that could impose adverse health hazard.

Multicomponent cis- and trans-Aziridinatons in the Syntheses of All Four Stereoisomers of Sphinganine.

All four stereoisomers of sphinganine can be synthesized by a multicomponent aziridination of an aldehyde, an amine and an α-diazo carbonyl compound mediated by a BOROX catalyst with high asymmetric induction (≥96% ee). The threo isomers are available from ring-opening of cis-aziridines by an oxygen nucleophile with inversion at the C-3 position and the erythro-isomers are likewise available from trans-aziridines.

A socio-economic study along with impact assessment for laterite based technology demonstration for arsenic mitigation.

Arsenic contamination mitigation technologies have been adsorption-based, but the most widely-used and traditionally available adsorbents suffered inherent limitations, including cost infeasibility and problems associated with regeneration and disposal of the spent adsorbent. The present technology is based on indigenously developed activated laterite prepared from the naturally and abundantly available material, and can hence easily be scaled up for community usage and large scale implementation. The total arsenic removal capacity is 32.5mg/g, which is the highest among all naturally occurring arsenic adsorbents. A major issue in earlier adsorbents was that during regeneration, the adsorbed arsenic would be released back into the environment (leaching), and would eventually contaminate the groundwater again. But the adsorbent in this filter does not require regeneration during its five-year lifespan and does not leach upon disposal. An attempt is made to test and demonstrate the practical implementation of the technology - its effectiveness and viability in three community (primary schools - one in Malda and two in north 24 Parganas, West Bengal, India) and 20 household filters, catering to over 5000 people in different areas of West Bengal exposed to high arsenic contamination of groundwater (ranging from 0.05 to 0.5mg/l). The work also focuses on the social impact of the real life technological solution on the lives on the affected people in the worst hit arsenic affected communities, perhaps the greatest public health risk emergency of the decade.

Inhibition of the multidrug efflux pump LmrS from Staphylococcus aureus by cumin spice Cuminum cyminum.

Staphylococcus aureus is a serious causative agent of infectious disease. Multidrug-resistant strains like methicillin-resistant S. aureus compromise treatment efficacy, causing significant morbidity and mortality. Active efflux represents a major antimicrobial resistance mechanism. The proton-driven multidrug efflux pump, LmrS, actively exports structurally distinct antimicrobials. To circumvent resistance and restore clinical efficacy of antibiotics, efflux pump inhibitors are necessary, and natural edible spices like cumin are potential candidates. The mode of cumin antibacterial action and underlying mechanisms behind drug resistance inhibition, however, are unclear. We tested the hypothesis that cumin inhibits LmrS drug transport. We found that cumin inhibited bacterial growth and LmrS ethidium transport in a dosage-dependent manner. We demonstrate that cumin is antibacterial toward a multidrug-resistant host and that resistance modulation involves multidrug efflux inhibition.

Catalyst-Controlled Multicomponent Aziridination of Chiral Aldehydes.

A highly diastereoselective and enantioselective method for the multicomponent aziridination of chiral aldehydes has been developed with BOROX catalysts of the VANOL (3,3'-diphenyl-2,2'-bi-1-naphthol) and VAPOL (2,2'-diphenyl-(4-biphenanthrol)) ligands. Very high to perfect catalyst control is observed with most all substrates examined including aldehydes with chiral centers in the α- and ß-positions. High catalyst control was also observed for a number of chiral heterocyclic aldehydes allowing for the preparation of epoxy aziridines, bis(aziridines) and ethylene diaziridines. Application of this reaction in the synthesis of ß3 -homo-d-alloisoleucine and ß3 -homo-l-isoleucine is reported.

Inactivation of Pseudomonas aeruginosa by Chitosan Coated Iron Oxide Nanoparticles.

BACKGROUND: Pseudomonas aeruginosa is one of the potent opportunistic pathogens associated with respiratory and urinary tract infection. The bacterium owes its pathogenicity due to the intrinsic resistance to antibiotics and disinfectants. OBJECTIVE: The present study is focused on the synthesis of antibacterial chitosan coated iron oxide nanoparticles for rapid inactivation of Pseudomonas aeruginosa. We have discussed the relevant patents on synthesis and antibacterial potential of metallic nanoparticles and chitosan. METHOD: Chitosan coated iron oxide nanoparticles were synthesized by coprecipitation method at room temperature using non-toxic chitosan and iron salts in alkali media. The particles were characterized and evaluated for antibacterial property against Pseudomonas aeruginosa. RESULTS: The average size of the particles was measured as 52 nm. The surface area of the coated particles was as high as 90 ±5 m2/g. FTIR spectra confirmed the coating of chitosan on nanoparticles. The coated particles showed excellent antibacterial activity against the bacteria. The minimum inhibitory concentration of the coated particles was 105)µg mol-1. The morphological alteration and cytoplasmic leakage of bacteria were confirmed by SEM image and release of intracellular constituents, respectively. Higher 260 nm absorbance value confirmed stronger antibacterial activity of the coated nanoparticles as compared to pure chitosan and bare iron oxide nanoparticles. CONCLUSION: The study indicated that chitosan coated iron oxide nanoparticles have superior antibacterial property as compared to pure chitosan and iron oxide nanoparticles.

Inactivation of Pseudomonas aeruginosa by chitosan coated iron oxide nanoparticles.

BACKGROUND: Pseudomonas aeruginosa is one of the potent opportunistic pathogens associated with respiratory and urinary tract infection. The bacterium owes its pathogenicity due to the intrinsic resistance to antibiotics and disinfectants. OBJECTIVE: The present study is focused on the synthesis of antibacterial chitosan coated iron oxide nanoparticles for rapid inactivation of Pseudomonas aeruginosa. We have discussed the relevant patents on synthesis and antibacterial potential of metallic nanoparticles and chitosan. METHOD: Chitosan coated iron oxide nanoparticles were synthesized by co-precipitation method at room temperature using non-toxic chitosan and iron salts in alkali media. The particles were characterized and evaluated for antibacterial property against Pseudomonas aeruginosa. RESULTS: The average size of the particles was measured as 52 nm. The surface area of the coated particles was as high as 90 ±5 m2/g. FTIR spectra confirmed the coating of chitosan on nanoparticles. The coated particles showed excellent antibacterial activity against the bacteria. The minimum inhibitory concentration of the coated particles was 105 µg mol-1. The morphological alteration and cytoplasmic leakage of bacteria were confirmed by SEM image and release of intracellular constituents, respectively. Higher 260 nm absorbance value confirmed stronger antibacterial activity of the coated nanoparticles as compared to pure chitosan and bare iron oxide nanoparticles. CONCLUSION: The study indicated that chitosan coated iron oxide nanoparticles have superior antibacterial property as compared to pure chitosan and iron oxide nanoparticles.

Comparative genome analysis of non-toxigenic non-O1 versus toxigenic O1 Vibrio cholerae.

Pathogenic strains of Vibrio cholerae are responsible for endemic and pandemic outbreaks of the disease cholera. The complete toxigenic mechanisms underlying virulence in Vibrio strains are poorly understood. The hypothesis of this work was that virulent versus non-virulent strains of V. cholerae harbor distinctive genomic elements that encode virulence. The purpose of this study was to elucidate genomic differences between the O1 serotypes and non-O1 V. cholerae PS15, a non-toxigenic strain, in order to identify novel genes potentially responsible for virulence. In this study, we compared the whole genome of the non-O1 PS15 strain to the whole genomes of toxigenic serotypes at the phylogenetic level, and found that the PS15 genome was distantly related to those of toxigenic V. cholerae. Thus we focused on a detailed gene comparison between PS15 and the distantly related O1 V. cholerae N16961. Based on sequence alignment we tentatively assigned chromosome numbers 1 and 2 to elements within the genome of non-O1 V. cholerae PS15. Further, we found that PS15 and O1 V. cholerae N16961 shared 98% identity and 766 genes, but of the genes present in N16961 that were missing in the non-O1 V. cholerae PS15 genome, 56 were predicted to encode not only for virulence-related genes (colonization, antimicrobial resistance, and regulation of persister cells) but also genes involved in the metabolic biosynthesis of lipids, nucleosides and sulfur compounds. Additionally, we found 113 genes unique to PS15 that were predicted to encode other properties related to virulence, disease, defense, membrane transport, and DNA metabolism. Here, we identified distinctive and novel genomic elements between O1 and non-O1 V. cholerae genomes as potential virulence factors and, thus, targets for future therapeutics. Modulation of such novel targets may eventually enhance eradication efforts of endemic and pandemic disease cholera in afflicted nations.

BOROX catalysis: self-assembled amino-BOROX and imino-BOROX chiral Brønsted acids in a five component catalyst assembly/catalytic asymmetric aziridination.

A five-component catalyst assembly/aziridination reaction is described starting from an aldehyde, an amine, ethyl diazoacetate, B(OPh)(3), and a molecule of a vaulted biaryl ligand (VAPOL or VANOL). A remarkable level of chemo-selectivity was observed since, while 10 different products could have resulted from various reactions between the five components, an aziridine was formed in 85% yield and 98% ee and only two other products could be detected in 3% yield. Studies reveal that the first in a sequence of three reactions is an exceedingly rapid amine-induced assembly of an amino-BOROX chiral Brønsted acid species from VAPOL and B(OPh)(3), which is followed by imine formation from the amine and aldehyde and the concomitant formation of an imino-BOROX chiral Brønsted acid and finally the reaction of the imine with ethyl diazoacetate mediated by the imino-BOROX catalyst to give aziridine-2-carboxylic esters with very high diastereo- and enantioselectivity.

Multicomponent catalytic asymmetric aziridination of aldehydes.

The first multicomponent catalytic asymmetric aziridination reaction is developed to give aziridine-2-carboxylic esters with very high diastereo- and enantioselectivity from aromatic and aliphatic aldehydes. This new method pushes the boundary of the aziridination reaction to substrates that failed with preformed imines.

Substrate-induced covalent assembly of a chemzyme and crystallographic characterization of a chemzyme-substrate complex.

A substrate induced covalent assembly of a highly organized chemzyme known to be effective in both catalytic asymmetric aziridination and aza Diels-Alder reactions is described and the information gained from which led to an efficient one-pot aziridination protocol. The crystal structures of two chemzyme-iminium complexes were elucidated by X-ray diffraction analysis that provides critical insights into the binding of the substrates with the chemzyme.

Seeking passe-partout in the catalytic asymmetric aziridination of imines: evolving toward substrate generality for a single chemzyme.

The asymmetric catalytic aziridination reaction (AZ reaction) of imines derived from dianisylmethyl (DAM) amine and tetra-methyldianisylmethyl (MEDAM) amine were examined with boroxinate catalysts prepared from both the VANOL and VAPOL ligands. This included an evaluation of different protocols for the preparation of the catalyst. The AZ reaction of DAM and MEDAM imines prepared from nine different aryl and aliphatic aldehydes were examined. The MEDAM imines were superior to the DAM imines in the AZ reaction, giving much higher asymmetric inductions and higher overall yields of aziridines. The MEDAM imines were found to also be superior to the previously studied diphenylmethyl (benzhydryl or Bh) and tetra-tert-butyldianisylmethyl (BUDAM) imines especially for imines derived from aliphatic aldehydes. The average asymmetric induction over the nine different MEDAM imines studied was 97% ee with the VAPOL catalyst and 96% ee with the VANOL catalyst. The MEDAM imines can be deprotected to give N-H aziridines in all cases except for some electron-rich aryl aldehydes. The MEDAM imines are much more reactive than benzhydryl imines, and this was most evident when a diazoacetate ester is replaced by a diazoacetamide. The less reactive diazoacetamides give very low yields in their reactions with benzhydryl imines but high yields with MEDAM imines.