Probability Distributions.- Linear Models for Regression.- Linear Models for Classification.- Neural Networks.- Kernel Methods.- Sparse Kernel Machines.- Graphical Models.- Mixture Models and EM.- Approximate Inference.- Sampling Methods.- Continuous Latent Variables.- Sequential Data.- Combining Models.

Pattern Recognition and Machine Learning

In the pursuit of new pharmaceuticals and agrochemicals, chemists in the life science industry require access to mild and robust synthetic methodologies to systematically modify chemical structures, explore novel chemical space, and enable efficient synthesis. In this context, photocatalysis has emerged as a powerful technology for the synthesis of complex and often highly functionalized molecules. This Review aims to summarize the published contributions to the field from the life science industry, including research from industrial-academic partnerships. An overview of the synthetic methodologies developed and strategic applications in chemical synthesis, including peptide functionalization, isotope labeling, and both DNA-encoded and traditional library synthesis, is provided, along with a summary of the state-of-the-art in photoreactor technology and the effective upscaling of photocatalytic reactions.

Photocatalysis in the Life Science Industry.

Click chemistry, proposed nearly 20 years ago, promised access to novel chemical space by empowering combinatorial library synthesis with a "few good reactions". These click reactions fulfilled key criteria (broad scope, quantitative yield, abundant starting material, mild reaction conditions, and high chemoselectivity), keeping the focus on molecules that would be easy to make, yet structurally diverse. This philosophy bears a striking resemblance to DNA-encoded library (DEL) technology, the now-dominant combinatorial chemistry paradigm. This review highlights the similarities between click and DEL reaction design and deployment in combinatorial library settings, providing a framework for the design of new DEL synthesis technologies to enable next-generation drug discovery.

DNA-Encoded Chemistry: Drug Discovery from a Few Good Reactions

DNA-encoded chemical libraries (DELs) represent a versatile and powerful technology platform for the discovery of small-molecule ligands to protein targets of biological and pharmaceutical interest. DELs are collections of molecules, individually coupled to distinctive DNA tags serving as amplifiable identification barcodes. Thanks to advances in DNA-compatible reactions, selection methodologies, next-generation sequencing, and data analysis, DEL technology allows the construction and screening of libraries of unprecedented size, which has led to the discovery of highly potent ligands, some of which have progressed to clinical trials. In this Review, we present an overview of diverse approaches for the generation and screening of DEL molecular repertoires. Recent success stories are described, detailing how novel ligands were isolated from DEL screening campaigns and were further optimized by medicinal chemistry. The goal of the Review is to capture some of the most recent developments in the field, while also elaborating on future challenges to further improve DEL technology as a therapeutic discovery platform.

DNA-Encoded Chemical Libraries: A Comprehensive Review with Succesful Stories and Future Challenges.

This review highlights the preparation of sodium sulfinates (RSO2Na) and their multifaceted synthetic applications. Substantial progress has been made over the last decade in the utilization of sodium sulfinates emerging as sulfonylating, sulfenylating or sulfinylating reagents, depending on reaction conditions. Sodium sulfinates act as versatile building blocks for preparing many valuable organosulfur compounds through S–S, N–S, and C–S bond-forming reactions. Remarkable advancement has been made in synthesizing thiosulfonates, sulfonamides, sulfides, and sulfones, including vinyl sulfones, allyl sulfones, and β-keto sulfones. The significant achievement of developing sulfonyl radical-triggered ring-closing sulfonylation and multicomponent reactions is also thoroughly discussed. Of note, the most promising site-selective C–H sulfonylation, photoredox catalytic transformations and electrochemical synthesis of sodium sulfinates are also demonstrated. Holistically, this review provides a unique and comprehensive overview of sodium sulfinates, which summarizes 355 core references up to March 2020. The chemistry of sodium sulfinate salts is divided into several sections based on the classes of sulfur-containing compounds with some critical mechanistic insights that are also disclosed.

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Yang Hongfang

Papers

Synthesis of 1,2-Amino Alcohols by Photoredox-Mediated Decarboxylative Coupling of α-Amino Acids and DNA-Conjugated Carbonyls.

A Strategy for the Synthesis of Sulfonamides on DNA.

Copper-Mediated DNA-Compatible One-Pot Click Reactions of Alkynes with Aryl Borates and TMS-N3.

DNA Compatible Intermolecular Wittig Olefination for the Construction of α, β-Unsaturated Carbonyl Compounds.

Solution-Phase DNA-Compatible Pictet-Spengler Reaction Aided by Machine Learning Building Block Filtering.