This thematic issue focuses on total synthesis as an enabling science. Total synthesis is the science of constructing molecules from simple starting materials and often deals with complex architectures that require a retrosynthetic problem-solving analysis. Total synthesis and the discovery of original synthetic methodologies have always been intimately linked. Old and recent achievements show that connections to other disciplines are important to the success of total synthesis and can be a source of new discoveries. Indeed, as a science allowing the preparation of useful functional compounds, it is strongly connected to biological and medicinal studies, while the development of natural-product-based tools for chemical biology often requires the construction of complex molecules (biology-driven total synthesis). Incidentally, the term "total synthesis" is not limited to natural products but also, sometimes, involves complex drugs. Furthermore, it is possible to test biosynthetic hypotheses concerning natural products through synthetic approaches (biomimetic synthesis). In addition, total syntheses have also been achieved with enzymes, strengthening the links to biology.

Total synthesis is not limited to academic laboratories but rather also pursued in industry, where a particular efficiency and economy of tasks is paramount. This requires permanent technological progress. Thus, the recent boom of machine learning and computational chemistry for retrosynthetic analyses and beyond foreshadows a renew interests to harvest increasingly complex synthetic strategies for industrial processes. In terms of discoveries in organic chemistry, total synthesis is a fruitful feed, and serendipity has well been exploited. Even dead ends, yet always heartbreaking for synthetic chemists, still provide a wealth of useful information for the chemical community. Finally, this is not to forget that organic chemistry, which is above all an experimental science, is performed daily by researchers in the laboratory, and some of these life stories can be truly inspiring to current and future generations. This thematic issue anticipates articles covering any of these remarks in the form of original research papers and reviews. In addition, submissions that highlight key topics and provide accounts and insights, or even biographical articles based on scientific data and/or evidence, are welcome.