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The development of several unique strategies and tactics for the synthesis of α-pinene isotopologues that has culminated in access to all eight possible isomers with deuterium incorporated selectively at each available carbon atom is described. Access to this library of isotopologues provides new tools to more fully investigate the atmospheric autoxidation of α-pinene, a complex process that plays a major role in the formation of secondary organic aerosol in the Earth's atmosphere.

Reported here are substrate-dictated rearrangements of chrysanthenol derivatives prepared from verbenone to access complex bicyclic frameworks. These rearrangements set the stage for a 10-step formal synthesis of the natural product xishacorene B. Key steps include an anionic allenol oxy-Cope rearrangement and a Suárez directed C-H functionalization. The success of this work was guided by extensive computational calculations which provided invaluable insight into the reactivity of the chrysanthenol-derived systems, especially in the key oxy-Cope rearrangement.

Retrosynthetic analysis is a cornerstone of modern natural product synthesis, providing an array of tools for disconnecting structures. However, discussion of retrosynthesis is often limited to the reactions used to form selected bonds in the forward synthesis. This review details three strategies for retrosynthesis, focusing on how they can be combined to plan the synthesis of polycyclic natural products, such as atropurpuran and the related arcutane alkaloids. Recent syntheses of natural products containing the arcutane framework showcase how these strategies for retrosynthesis can be combined to plan the total synthesis of highly caged scaffolds. Comparison of multiple syntheses of the same target provides a unique opportunity for detailed analysis of the impact of retrosynthetic disconnections on synthesis outcomes.

A key challenge in the synthesis of diterpenoid alkaloids lies in identifying strategies that rapidly construct their multiply bridged polycyclic skeletons. Existing approaches to these structurally intricate secondary metabolites are discussed in the context of a "bond-network analysis" of molecular frameworks, which was originally devised by Corey some 40 years ago. The retrosynthesis plans that emerge from a topological analysis of the highly bridged frameworks of the diterpenoid alkaloids are discussed in the context of eight recent syntheses of hetidine and hetisine natural products and their derivatives. This Minireview highlights the extent to which network analyses of the type described here sufficed for designing synthesis plans, as well as areas where they had to be amalgamated with functional group oriented synthetic planning considerations.

A copper-mediated conjugate addition of electron-rich aryl groups into a complex vinyl nitrile using arylmagnesium bromides is reported. The conjugate addition adducts were advanced toward the synthesis of designed aconitine-type analogues. The variation in oxygenation patterns on the arene coupling partner, introduced through the current conjugate addition approach, may ultimately provide insight into structure-activity relationships of the diterpenoid alkaloids.

The secondary metabolites that comprise the diterpenoid alkaloids are categorized into C18, C19, and C20 families depending on the number of contiguous carbon atoms that constitute their central framework. Herein, we detail our efforts to prepare these molecules by chemical synthesis, including a photochemical approach, and ultimately a bioinspired strategy that has resulted in the development of a unifying synthesis of one C18 (weisaconitine D), one C19 (liljestrandinine), and three C20 (cochlearenine, paniculamine, and N-ethyl-1α-hydroxy-17-veratroyldictyzine) natural products from a common intermediate.

A key challenge in the synthesis of diterpenoid alkaloids lies in identifying strategies that rapidly construct their multiply bridged polycyclic skeletons. Existing approaches to these structurally intricate secondary metabolites are discussed in the context of a "bond-network analysis" of molecular frameworks, which was originally devised by Corey some 40 years ago. The retrosynthesis plans that emerge from a topological analysis of the highly bridged frameworks of the diterpenoid alkaloids are discussed in the context of eight recent syntheses of hetidine and hetisine natural products and their derivatives. This Minireview highlights the extent to which network analyses of the type described here sufficed for designing synthesis plans, as well as areas where they had to be amalgamated with functional group oriented synthetic planning considerations., (© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

The secondary metabolites that comprise the diterpenoid alkaloids are categorized into C 18 , C 19 , and C 20 families depending on the number of contiguous carbon atoms that constitute their central framework. Herein, we detail our efforts to prepare these molecules by chemical synthesis, including a photochemical approach, and ultimately a bioinspired strategy that has resulted in the development of a unifying synthesis of one C 18 (weisaconitine D), one C 19 (liljestrandinine), and three C 20 (cochlearenine, paniculamine, and N-ethyl-1α-hydroxy-17-veratroyldictyzine) natural products from a common intermediate.