Methodology Scheme Research Articles

Synthesis of the Thiazolone Analogue of the Acetylcholinesterase Inhibitor, Huperzine A

AbstractThe preparation of an analogue 3a of the acetylcholinesterase inhibitor, huperzine A (1), is described in which the pyridinone moiety of the natural product is replaced with a thiazolone moiety. The synthesis started from cyclohexane‐1,4‐dione monoethylene ketal (7) by first annulating the thiazole ring using the Gewald protocol (→ 8; Scheme 1) and then constructing the bicyclo[3.3.1]nonane substructure using our previously described Michael addition/aldol condensation methodology (Scheme 3). The central problem was the protection of the thiazolone carbonyl group; only the 2‐unsubstituted thiazole survived the reaction conditions of the first half of the synthesis. Refunctionalization was later effected by lithiation and subsequent chlorination with hexachloroethane (30→31). Compound 3a was ineffective in the acetylcholinesterase inhibition assay in concentrations up to 14 μM.

A Methodology and Encoding Scheme for Evaluating the Usability of Graphical, Direct Manipulation Style Interfaces

A model-based method for assessing the usability of graphical, direct manipulation style interfaces was developed and applied to a military airspace scheduling system. The method involves collecting and integrating verbal protocol data and mouse/keystroke files, and having an analyst familiar with the task, the data, and Norman's (1986) user activity model review the data and make determinations on what the data mean in terms of the model. A hierarchical encoding scheme based on the model is then applied to the integrated data to structure the human-computer interaction (HCI) process at a detailed interaction level. Meaningful patterns can be identified, frequency of events per task, and number of actions per intention can be calculated at various levels in the hierarchical breakdown, highlighting potential usability problems or instances of indirectness. Repetitious sequences, for example, could imply a missing high-level task domain object or an inability to group objects for application of a single action. Detailed model-based error encodings reflect user-system interface difficulties not only in the execution stage of HCI but in the psychological stages as well. The types of usability problems identified and the advantages of the method are discussed. Based on these results, we have begun developing a multi-media tool to support application of the method.

Identification, classification and management of errors in automated component assembly tasks

Manufacturing industries are turning to advanced technologies in order to improve performance. While this is feasible in many industrial applications, it creates new problems in assembly. In particular, handling errors in automated assembly is crucial to the development of viable automatic assembly systems. Although many writers have recognized this as a problem, few have attempted to deal with it in a systematic fashion. In this preliminary paper the subject of errors in automated assembly is discussed, and a scheme for the classification of errors applicable to automated assembly systems is presented. It is suggested that errors are context dependent, and it is plausible to classify errors in close relation to a generic classification of assembly operations. Task analysis methods are used to define specific operational contexts, and which allow us to postulate likely errors. A worked example of this methodology and classification scheme is presented, using the traditional ‘peg-in-hole’ problem. The methodology facilitates a structured analysis of error conditions associated with particular assembly tasks, and by accounting for system characteristics it will then be possible to develop appropriate error management strategies. This work is currently being applied to characterize the Alvey Robotic Assembly Cell, as developed by Lucas Engineering and Systems Limited, and currently sited here at Birmingham. The overall aim of the work is towards the development of the EMA (error management) expert system that will assist the designer and go towards providing intelligent control systems capable of detecting imminent errors, taking corrective actions and/or recovering from them.

Combined directed metalation - cross coupling strategies. A regiospecific route to heteroring-annelated artho-naphthoquinones and a short synthesis of β-lapachone

A general combined metalation - cross coupling methodology ( Scheme 1) for the regiospecific construction of heteroring fused o-naphthoquinones 8 is described and its application to a short synthesis of the antimalarial/antitumor natural product β-lapachone ( 14) is demonstrated.

A Facile Synthesis of Optically Pure (−)‐(S)‐Ipsenol Using a Chiral Titanium Complex

AbstractA stereocontrolled synthetic route to optically pure (−)‐(S)‐ipsenol (1), the pheromone of Pityokteines curvidens and various other bark‐beetle species is described. Key step of the synthesis is an enantioselective aldol reaction using a chiral titanium–carbohydrate complex (Scheme 1). The carboxylate function of the optically pure β‐hydroxy acid 5 thus obtained in mol quantities is then elaborated to the diene moiety by standard methodology (Scheme 2).