Target-oriented total synthesis of architecturally complex organic molecules possesses a rich and long-standing history. Today, it remains a pivotal component of synthetic chemistry and its various interconnected disciplines. Over the past decades, the development of ambitious synthetic pathways has enabled access to highly complex and intricate molecular structures, consistently advancing the boundaries of efficiency and creativity by integrating modern methodologies and innovative strategies. In this context, while adhering to the guiding principles of the “Corey school” of retrosynthetic analysis, “concept-based” synthetic design has received widespread attention and served a parallel role in the design of synthetic pathways. Notable examples include “biomimetic and bioinspired synthesis”, “protecting-group-free synthesis”, “collective and divergent synthesis”, “cascade and multi-component synthesis”, and “desymmetrization and symmetry-based synthesis”. Each of these concepts has established a significant role in target-oriented organic synthesis, demonstrating broad applicability across structurally diverse compound classes. Moreover, emerging synthetic concepts are also accounting for notable contributions to the field, including “two-phase terpene synthesis” (Baran), “network analysis synthesis of polycyclic compounds” (Sarpong), as well as strategies based on “late-stage functionalization” and “molecular editing.”

This thematic issue, titled “Concept-driven strategies in target-oriented synthesis”, aims to showcase a meticulously curated collection of recent advancements in target-oriented synthesis presented by leading experts in the field. These contributions serve as a testament to the state-of-the-art practices in target-oriented synthesis and underscore the vibrancy and immense potential of this dynamic field. It is anticipated that this thematic issue will inspire practitioners, students, and total synthesis enthusiasts at all levels, fostering a deeper interest in the discipline and encouraging the pursuit of new frontiers in chemical synthesis.

Submission deadline: October 31, 2025