49 research outputs found

    Shorter and Improved Access to the Key Tetracyclic Core of Sarpagine-Macroline-Ajmaline Indole Alkaloids: the Total Synthesis of Alkaloids Macrocarpines A-g, Talcarpine, N(4)-methyl-n(4),21-secotalpinine, Deoxyperaksine, Dihydroperaksine, Talpinine, O-acetyltalpinine, and N(4)-methyltalpinine

    Get PDF
    Extension of the asymmetric Pictet-Spengler (P-S) reaction to bulkier Nb-alkylated tryptophan derivatives resulted in a shorter and improved stereospecific access to the key bicyclo[3.3.1]nonane framework of bioactive C-19 methyl substituted sarpagine/macro-line/ajmaline indole alkaloids with excellent diastereoselectivity via internal asymmetric induction. The asymmetric Pictet-Spengler/Dieckmann protocol with bulky Nb-alkyl substituted systems enabled a more direct and two-step shorter route to this key architecture. Complete stereocontrol of the C-19 methyl function in either the α- or β-configuration was achieved which would enable one to gain rapid access to the crucial intermediates for the total synthesis of any member of this group of seventy alkaloids. The asymmetric Pictet-Spengler (P-S) reaction of chiral Nb-ethynyl substituted tryptophan methyl ester derivatives (from both D- and L-tryptophan) with a simple aliphatic aldehyde, exhibited unprecedented stereoselectivity toward either of the diastereomeric products. A simple variation of conditions altered the outcome of the cyclization from either 100% trans-selective to 100% cis-selective originating entirely from internal asymmetric induction under mild conditions. This resulted in the highly efficient access to both 1,3-cis-(1,2,3-trisubstituted tetrahydro-β-carbolines, THβCs) and 1,3-trans-(1,2,3-trisubstituted THβCs). By exploiting this very useful ambidextrous-diastereoselectivity, one can set the crucial C-3 and C-5 stereocenters of the C-19 methyl substituted sarpagine-macroline-ajmaline alkaloids beginning either with the DNA-encoded and cheaper L-(-)-tryptophan, as well as optionally from commercially available D-(+)-tryptophan. The unnatural enantiomers of bioactive natural alkaloids are potential drug candidates. The unnatural enantiomer of alkaloids may have similar drug-like properties or even better than the natural counterpart depending on the rate of metabolism. The ambidextrous Pictet-Spengler reaction has enabled one to access the key intermediates with the bicyclo[3.3.1] framework starting from either the natural L-tryptophan or the commercially available D-tryptophan. Logically, the ambidextrous nature of this P-S process would allow one ready access to the unnatural enantiomers of the alkaloids from this subgroup. As the proof of concept, which is important to illustrate the full potential of the ambidextrous P-S reaction, both D-tryptophan and L-tryptophan were employed to synthesize the key intermediates toward the natural enantiomers of alkaloids. Now the enantiomeric series of the same key intermediates could also be synthesized from both D- and L-tryptophan in high yield and optical purity via this P-S/Dieckmann protocol. One can make either the natural or the unnatural alkaloids from either starting amino acid ester, stereo and enantiospecifically at will. After gaining access to the bicyclo[3.3.1] framework via the ambidextrous Pictet-Spengler reaction, the focus turned to the completion of the total synthesis of a number of C-19 methyl substituted sarpagine/macroline/ajmaline indole alkaloids. As a step towards that, alkaloids with Na-H, Nb-CH3 substitution patterns were both of interest via the same route. An enolate driven copper-mediated cross-coupling process enabled a cheaper and greener access to the key pentacyclic intermediates required for the enantiospecific total synthesis of a number of C-19 methyl substituted sarpagine/macroline indole alkaloids. Replacement of palladium (60-68% yields) with copper iodide (82-89% yields) resulted in a much cleaner process in high yield. The formation of an unusual seven-membered cross-coupling product was completely inhibited by using TEMPO as a radical scavenger. Further functionalization led to the first enantiospecific total synthesis of macrocarpines D and E. After the successful completion of the total synthesis of several C(19)-methyl Na-H, Nb-CH3 substituted alkaloids, focus turned toward the total synthesis of a number of alkaloids bearing the Na-CH3, Nb-CH3 substitution pattern. In addition, a pair of sarpagine alkaloids, termed dihydroperaksine and deoxyperaksine bore the C-19 (S)-methyl substitution; this was opposite to the chirality in many of the alkaloids of this group. Access to these alkaloids in high yields illustrated the versatility of the strategy developed here to access alkaloids with either C-19 (S)- or (R)-methyl substituents. This effort resulted in the successful total synthesis of several bioactive alkaloids, as well as correction of the literature values for macrocarpine A and N4-methyl-N4,21-secotalpinine. A late stage Nb-demethylation of macrocarpines A and C afforded the Nb-H bearing alkaloids macrocarpines F and G, respectively. A similar transformation enabled access to the bioactive alkaloid talpinine from both talcarpine and N4-methyl-N4,21-secotalpinine. The other bioactive alkaloid O-acetyltalpinine was also prepared from synthetic talpinine in high yield. Finally, the unusual quaternary Nb-nitrogen function containing alkaloid N4-methyltalpinine that exhibited potent NFκB inhibitory activity was completed via facile transformations in excellent yield

    EMG Signal Classification for Neuromuscular Disorders with Attention-Enhanced CNN

    Full text link
    Amyotrophic Lateral Sclerosis (ALS) and Myopathy present considerable challenges in the realm of neuromuscular disorder diagnostics. In this study, we employ advanced deep-learning techniques to address the detection of ALS and Myopathy, two debilitating conditions. Our methodology begins with the extraction of informative features from raw electromyography (EMG) signals, leveraging the Log-spectrum, and Delta Log spectrum, which capture the frequency contents, and spectral and temporal characteristics of the signals. Subsequently, we applied a deep-learning model, SpectroEMG-Net, combined with Convolutional Neural Networks (CNNs) and Attention for the classification of three classes. The robustness of our approach is rigorously evaluated, demonstrating its remarkable performance in distinguishing among the classes: Myopathy, Normal, and ALS, with an outstanding overall accuracy of 92\%. This study marks a contribution to addressing the diagnostic challenges posed by neuromuscular disorders through a data-driven, multi-class classification approach, providing valuable insights into the potential for early and accurate detection

    Service Quality Dimensions of Retailing - A Study on Retail Chain Stores in Chittagong

    Get PDF
    Service quality is a critical component of customer perceptions about the service. The performance and quality parameters of any service are dependent on customer expectations and how efficiently and satisfactorily the service firm is able to serve its customers. This study employs the SERVQUAL method to study service quality aspects of retail stores in Chittagong, Bangladesh. The traditional quality dimensions for assessing the service quality have been modified to assess the customers’ service needs and satisfaction in the retail sector. The results showed that a high positive correlation existed between various service dimensions, and that customers’ evaluation of service quality was more or less similar across different age groups. This study aims at identifying components of retail service quality in retail chain store in Chittagong. A survey of 412 shoppers in various retail chain store in Chittagong has resulted that service quality of retain chain store composes of 5 dominant factors namely Tangibility, Reliability, Assurance, Responsiveness and Empathy. Keywords: SERVQUAL; Retailer; Interactions; Behavior; Retailin

    ResEMGNet: A Lightweight Residual Deep Learning Architecture for Neuromuscular Disorder Detection from Raw EMG Signals

    Full text link
    Amyotrophic Lateral Sclerosis (ALS) and Myopathy are debilitating neuromuscular disorders that demand accurate and efficient diagnostic approaches. In this study, we harness the power of deep learning techniques to detect ALS and Myopathy. Convolutional Neural Networks (CNNs) have emerged as powerful tools in this context. We present ResEMGNet, designed to identify ALS and Myopathy directly from raw electromyography (EMG) signals. Unlike traditional methods that require intricate handcrafted feature extraction, ResEMGNet takes raw EMG data as input, reducing computational complexity and enhancing practicality. Our approach was rigorously evaluated using various metrics in comparison to existing methods. ResEMGNet exhibited exceptional subject-independent performance, achieving an impressive overall three-class accuracy of 94.43\%

    Analysis of Call Data Record (CDR) using Hadoop Cluster

    Get PDF
    The management of big data is the most important issue for this decade since the real world applications are generating very large scale of data in petabytes and zetabytes scale. Most popular solution of big data management is a system based on Hadoop Distributed File System. However, implementing enterprise level solution is a challenge because of the production of such huge data. In this project, we employ Hadoop cluster to the telecommunication data since it produces a huge amount of log data regarding to customer calls as well as network equipment. To emphasize more realistic solution we ponder on call data details for our Big Data application. In this project, we have acquired real-time Call Data Record (CDR) data for our implementation from telco operator named Banglalink who is operating 30 million users in Bangladesh. To narrow down the scope, CDR data analytics using Hadoop cluster can result top callers to promote customer experience. This implement can also help Banglalink to implement similar application for backup data warehouse using Hadoop cluster for CDR analytics

    Consumer Attitude Towards the Cell Phone: A study on Young Generations of Chittagong Metropolitan City, Bangladesh

    Get PDF
    Due to increased competition, locally as well as internationally, organizations need a distinguishing element that will keep consumers identifying and buying their product. This study employs to analyze the relationship between demographic variables on the brand preference and is identifying the attributes that affect the choice behavior of mobile hand set as well as why the young consumers give special emphasis to some particular factors in Chittagong metropolitan city. From the study we see that though both male and female respondents now using Nokia (57.92%) hand set but about 50.61% of male & 59.85% of female respondent choices Samsung mobile set as their most favorite brand to next purchase because of android operating system. We also see that both newspaper (39.82%) and television (36.18%) has a great influence over the respondents to choose the above mentioned mobile hand set as their favorite brand. About 67.16 % of respondents are willing to spend money more than Tk. 10,000 to get the test of latest features provided by the various mobile set companies. JEL Classification Code:  E3

    Biatrial Myxoma in a Young Male Patient

    Get PDF

    Consumer Attitude Towards the Cell Phone: A study on Young Generations of Chittagong Metropolitan City, Bangladesh

    Get PDF
    Due to increased competition, locally as well as internationally, organizations need a distinguishing element that will keep consumers identifying and buying their product. This study employs to analyze the relationship between demographic variables on the brand preference and is identifying the attributes that affect the choice behavior of mobile hand set as well as why the young consumers give special emphasis to some particular factors in Chittagong metropolitan city. From the study we see that though both male and female respondents now using Nokia (57.92%) hand set but about 50.61% of male & 59.85% of female respondent choices Samsung mobile set as their most favorite brand to next purchase because of android operating system. We also see that both newspaper (39.82%) and television (36.18%) has a great influence over the respondents to choose the above mentioned mobile hand set as their favorite brand. About 67.16 % of respondents are willing to spend money more than Tk. 10,000 to get the test of latest features provided by the various mobile set companies
    corecore