Computer-aided Design Synthesis Research Articles

Node-Aligned Graph-to-Graph: Elevating Template-free Deep Learning Approaches in Single-Step Retrosynthesis.

Single-step retrosynthesis in organic chemistry increasingly benefits from deep learning (DL) techniques in computer-aided synthesis design. While template-free DL models are flexible and promising for retrosynthesis prediction, they often ignore vital 2D molecular information and struggle with atom alignment for node generation, resulting in lower performance compared to the template-based and semi-template-based methods. To address these issues, we introduce node-aligned graph-to-graph (NAG2G), a transformer-based template-free DL model. NAG2G combines 2D molecular graphs and 3D conformations to retain comprehensive molecular details and incorporates product-reactant atom mapping through node alignment, which determines the order of the node-by-node graph outputs process in an autoregressive manner. Through rigorous benchmarking and detailed case studies, we have demonstrated that NAG2G stands out with its remarkable predictive accuracy on the expansive data sets of USPTO-50k and USPTO-FULL. Moreover, the model's practical utility is underscored by its successful prediction of synthesis pathways for multiple drug candidate molecules. This proves not only NAG2G's robustness but also its potential to revolutionize the prediction of complex chemical synthesis processes for future synthetic route design tasks.

Tools for Synthesis Planning, Automation, and Analytical Data Analysis.

Computer-aided synthesis design, automation, and analytics assisted by machine learning are promising resources in the researcher's toolkit. Each component may alleviate the chemist from routine tasks, provide valuable insights from data, and enable more informed experimental design. Herein, we highlight selected works in the field and discuss the different approaches and the problems to which they may apply. We emphasize that there are currently few tools with a low barrier of entry for non-experts, which may limit widespread integration into the researcher's workflow.

Retrosynthesis from transforms to predictive sustainable chemistry and nanotechnology: a brief tutorial review

Retrosynthesis is a tool initially developed to simplify the planning of the synthesis of organic molecules. With the progress of computer-aided synthesis design (CASD), its development will be predictive green and sustainable CASD.

Guiding solvothermal synthesis

Machine Learning Machine learning is rapidly revolutionizing computer-aided synthesis design, occasionally producing vivid use cases when the reaction parameters important for the synthesis are hidden in a complex chemical space. Xie et al. report a machine learning–assisted framework for the synthesis of metal-organic nanocapsules (MONCs), giant molecular building units potentially useful in different fields, based on predicting the crystallization propensity using experimental attempts as a training dataset. Machine-learning algorithms achieve prediction accuracies of more than 90%, considerably outperforming trained chemists, and the generated synthesis parameters direct solvothermal crystallization to new structures of MONCs. The proposed strategy for the discovery of new materials can be applied more broadly beyond MONCs. J. Am. Chem. Soc. 10.1021/jacs.9b11569 (2019).

MOTO-X: A Multiple-Output Transistor-Level Synthesis CAD Tool

Transistor count minimization is an important goal as very-large-scale integration technology approaches its technical and physical limits. In this paper, we present a computer-aided design synthesis tool that tries to minimize the number of transistors required to implement a given multiple-output logic function. The proposed transistor-level synthesis approach goes beyond the traditional series-parallel design style and allows for extensive bridging. It starts from a sum-of-products expression for each output, allowing also for don’t care terms, and produces a transistor network with a small number of transistors to implement all outputs jointly under a user-specified bound on the number of transistors in series to avoid long charge/discharge paths. Experimental results on previously examined multioutput functions and case studies (full adder, Gray/binary counter, and seven-segment display) demonstrate the benefit of the approach.

Route Design in the 21st Century: The ICSYNTH Software Tool as an Idea Generator for Synthesis Prediction

The new computer-aided synthesis design tool ICSYNTH has been evaluated by comparing its performance in predicting new ideas for route design to that of historical brainstorm results on a series of commercial pharmaceutical targets, as well as literature data. Examples of its output as an idea generator are described, and the conclusion is that it adds appreciable value to the performance of the professional drug research and development chemist team.

A Short Review of Chemical Reaction Database Systems, Computer-Aided Synthesis Design, Reaction Prediction and Synthetic Feasibility.

This article is the text for a pedagogical lecture to be given at the Strasbourg Summer School in Chemoinformatics in June 2104. It covers a very wide range of reaction topics including structure and reaction representation, reaction centers, atom-to-atom mapping, reaction retrieval systems, computer-aided synthesis design, retrosynthesis, reaction prediction and synthetic feasibility. In the time available the coverage of each topic can only be cursory; the main usefulness of this article to the research community is the extensive bibliography.

Computer-aided design synthesis: an application of shape grammars

Computer-aided design systems enable the creation of digital product definitions that are widely used throughout the design process. Typically, such product definitions are created after the bulk of [shape] designing has been completed because their creation requires a detailed knowledge of the shape that is to be defined. Shape grammars have been applied in a range of domains to generate design shapes that conform to a given style early in design processes. A key challenge that restricts their implementation lies in the detection of embedded shapes, sub-shapes, which are manipulated according to shape rules to create new shapes. The automatic detection of sub-shapes is an open research question within the shape grammar community. The research reported in this paper explored the use of computer vision techniques to address this problem; the results achieved to date show real promise. An early prototype is presented and demonstrated on a designer's sketches.

ChemInform Abstract: Are Microreactors Useful for Organic Synthesis?

Recent developments regarding microreactors of which reaction volume is at μl order are reviewed from the viewpoint of system design for laboratory automation which is useful for process chemistry. Physical and chemical phenomena at μm level (size effects), structural elements, and fabrication methods concerning microreactors are summarized. Applied reaction examples classified into seven categories are also surveyed. The advantages of microreactors are (1) easy of rapid and precise control of temperature, which is helpful in obtaining of heat-unstable compounds, (2) high reaction rate, (3) high yield of reaction products (the author's hypothesis) and (4) easy of scale-up of reaction volume without complicated calculations in chemical engineering. The productivity of chemical compounds by microreactors is much enough for cost-effective fine chemicals. The importance of combination of computer-aided synthesis design and microreactors is also pointed out to swiftly validate the candidate reaction routes presented. In conclusion, microreactors have great potential for serving as a powerful tool for organic synthesis research.

マイクロリアクタは有機合成に役立つか

Recent developments regarding microreactors of which reaction volume is at μl order are reviewed from the viewpoint of system design for laboratory automation which is useful for process chemistry. Physical and chemical phenomena at μm level (size effects), structural elements, and fabrication methods concerning microreactors are summarized. Applied reaction examples classified into seven categories are also surveyed. The advantages of microreactors are (1) easy of rapid and precise control of temperature, which is helpful in obtaining of heat-unstable compounds, (2) high reaction rate, (3) high yield of reaction products (the author's hypothesis) and (4) easy of scale-up of reaction volume without complicated calculations in chemical engineering. The productivity of chemical compounds by microreactors is much enough for cost-effective fine chemicals. The importance of combination of computer-aided synthesis design and microreactors is also pointed out to swiftly validate the candidate reaction routes presented. In conclusion, microreactors have great potential for serving as a powerful tool for organic synthesis research.

Computer-aided synthesis design at RISC-Linz: automatic extraction and use of reaction classes

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Synthesis, design, and construction of ultra-wide-band nonuniform quadrature directional couplers in inhomogeneous media

A computer-aided synthesis design procedure is given for nonuniform quadrature directional couplers in inhomogeneous media. A wiggly geometry is used which effectively slows the odd-mode phase velocity to match the even-mode phase velocity. The wiggly geometry results in improved isolation and increased effective dielectric constant. This technique provides a shorter coupler length due to increased effective dielectric constant. Cubic splines of strip width, strip spacing, and wiggle depth as functions of coupling coefficient are computed using static capacitances of uniform coupled lines. These functions are then used as synthesis functions to evaluate the continuous physical parameters of nonuniform coupled lines by using the continuously varying coupling coefficient. A nonuniform interdigitated coupler is introduced to realize the tight coupling values. >

A review of chemical structure retrieval systems

AbstractThis paper decribes the development and current state‐of‐the‐art in computerized systems for the storage and retrieval of chemical structure information. The main types of machine‐readable structure representation — fragmentation codes, linear notations and connection tables — are described, together with the retrieval algorithms which are used to provide structure and substructure search facilities. Current research work in chemical structure retrieval includes the development of techniques for the representation and searching of the generic structures which occur in chemical patents, for searching files of three‐dimensional structures, for ranking searches designed to identify compounds structurally similar to a given query compound, and the use of parallel computers to increase the efficiency of substructure searching. Chemical structure handling techniques are also applicable in a range of application areas, including chemical reaction indexing, computer‐aided synthesis design and structure elucidation, and substructural analysis methods for the study of quantitative structure—activity relationships.