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Herein, we present a unified chemical synthesis of three subgroups of cephalotaxus diterpenoids. Key to the success lies in adopting a synthetic strategy that is inspired by biosynthesis but is opposite in nature. By employing selective one‐carbon introduction and ring expansion operations, we have successfully converted cephalotane‐type C18 dinorditerpenoids (using cephanolide B as a starting material) into troponoid‐type C19 norditerpenoids and intact cephalotane‐type C20 diterpenoids. This synthetic approach has enabled us to synthesize cephinoid H, 13‐oxo‐cephinoid H, 7‐oxo‐cephinoid H, fortalpinoid C, 7‐epi‐fortalpinoid C, cephanolide E, and 13‐epi‐cephanolide E. Furthermore, through the development of an intermolecular asymmetric Michael reaction between β‐oxo esters and β‐substituted enones, we have achieved the enantioselective synthesis of advanced intermediates within our synthetic sequence, thus formally realizing the asymmetric total synthesis of the cephalotaxus diterpenoids family. [ABSTRACT FROM AUTHOR]

Secondary metabolites that have the same biological origin must share some relationship in their biosynthesis. Exploring this relationship has always been a significant task for synthetic biologists. However, from the perspective of synthetic chemists, it is equally important to propose, prove, or refute potential biosynthetic pathways in order to elucidate and understand the biosynthesis of homologous secondary metabolites. In this study, driven by the high structural similarity between the homologous Ganoderma meroterpenoids cochlearol B and ganocin B, two chemically synthetic strategies were designed and investigated sequentially for the synthesis of cochlearol B from ganocin B. These strategies include intramolecular metal‐catalyzed hydrogen atom transfer (MHAT) and intramolecular photochemical [2+2] cycloaddition. The aim was to reveal their potential biosynthetic conversion relationship using chemical synthesis methods. As a result, a highly efficient total synthesis of cochlearol B, cochlearol T, cochlearol F, as well as the formal total synthesis of ganocins A–B, and ganocochlearins C–D, has been achieved. Additionally, a novel synthetic approach for the synthesis of 6,6‐disubstituted 6H‐dibenzo[b,d]pyran and its analogues has been developed through palladium(II)‐catalyzed Wacker‐type/cross‐coupling cascade reactions. [ABSTRACT FROM AUTHOR]

Herein, we report a concise and divergent synthesis of the complex hasubanan alkaloids metaphanine and oxoepistephamiersine from commercially available and inexpensive cyclohexanedione monoethylene acetal. Our synthesis features a palladium‐catalyzed cascade cyclization reaction to set the tricyclic carbon framework of the desired molecules, a regioselective Baeyer–Villiger oxidation followed by a MeNH2 triggered skeletal reorganization cascade to construct the benzannulated aza[4.4.3]propellane, and a strategically late‐stage regio‐/diastereoselective oxidative annulation of sp3 C−H bond to form the challenging THF ring system and hemiketal moiety in a single step. In addition, a highly enantioselective alkylation of cyclohexanedione monoethylene acetal paved the way for the asymmetric synthesis of target molecular. [ABSTRACT FROM AUTHOR]

We briefly highlight our recent work on the total synthesis of six Ganoderma phenolic meroterpenoids: ganocins A–C, ganocochlearins A–D, and cochlearol T. Critical to this success was a bioinspired two-phase strategy that featured an early-stage rapid construction of a common planar tricyclic intermediate and late-stage highly selective transformations of this intermediate into various Ganoderma meroterpenoids. Key steps of the synthesis include a biomimetic ortho -quinone methide intramolecular hetero-Diels–Alder reaction, a Stahl-type oxidative aromatization, a nucleophilic dearomatization of a phenol, a regioselective 1,4-reduction of a dienone, a site-selective Mukaiyama hydration, and an intramolecular oxa-Michael addition/triflation cascade. [ABSTRACT FROM AUTHOR]

A divergent synthetic approach to six Ganoderma meroterpenoids, namely ganocins A–C, ganocochlearins C and D, and cochlearol T, has been developed for the first time. This synthetic route features a two‐phase strategy which includes early‐stage rapid construction of a common planar tricyclic intermediate followed by highly selective late‐stage transformations into various Ganoderma meroterpenoids. Key to the strategy are a bioinspired intramolecular hetero‐Diels–Alder reaction and Stahl‐type oxidative aromatization, allowing efficient formation of the common tricyclic phenol intermediate. A nucleophilic dearomatization of the phenol unit, combined with a regioselective 1,4‐reduction of the resulting dienone, enabled rapid access to ganocins B and C. Additionally, site‐selective Mukaiyama hydration, followed by an intramolecular oxa‐Michael addition/triflation cascade, served as a key strategic element in the chemical synthesis of ganocin A. [ABSTRACT FROM AUTHOR]

Synthetic studies toward the daphnane and tigliane diterpenes, a large family of natural products from the plant families Euphorbiaceae and Thymelaeaceae , are reported. Retrosynthetic analysis traced these molecules back to an aromatic precursor and several routes were explored in the forward direction to access such motifs. Two strategies ultimately proved capable of forging complex 5,7,6 -fused tricyclic ring systems, one of which proceeded in only seven steps. Image 1 [ABSTRACT FROM AUTHOR]

In this work, we present the details of the first unified chemical synthesis of cephalotaxus diterpenoids with three distinct carbon skeleton structures. Drawing on our previous synthesis of cephalotane-type C18 dinorditerpenoid and inspired by the proposed biosynthetic synthesis pathway, we formulated a biosynthetic reversed chemical synthetic strategy. This strategy facilitated the conversion of C18 dinorditerpenoid into troponoid-type C19 norditerpenoid and intact cephalotane-type C20 diterpenoid through pivotal one-carbon introduction and ring expansion reactions. In the synthesis of troponoid-type C19 norditerpenoid, we utilized TMSCHN 2 as one-carbon unit and meticulously examined the selective regulatory effect of halogen substituents in ring expansion and rearrangement reactions. This endeavor culminated in the successful synthesis of natural product molecules within this subclass, notably including cephinoid H and fortalpinoid C, marking the first chemical total synthesis in this line of research. In the investigation of intact cephalotane-type C20 diterpenoid synthesis, while adhering to the overall synthesis strategy, we initially pursued a ring expansion before carbon introduction approach, which proved unsuccessful. Subsequently, we explored a synthetic route of introducing carbon first and then expanding the ring, leading to a successful outcome and resulting in the first chemical total synthesis of the representative molecule cephanolide E within this subclass. Various challenges such as establishing crucial quaternary carbon stereocenters, selecting appropriate one-carbon units, and controlling ring expansion reactions were effectively addressed throughout this process. Moreover, enantioselective synthesis of natural products within this family was achieved through the development of asymmetric Michael reactions. A detailed research summary is presented for introducing the unified total synthesis of three subgroups of cephalotaxus diterpenoids, with a novel synthetic route possessing a reverse order with potential biosynthetic route. The troponoid-type C19 norditerpenoids cephinoid H and fortalpinoid C could be synthesized from cephalotane-type C18 dinorditerpenoid-cephanolide B through regioselective ring expansion modulated by introducing a chlorine atom at the C15 site. For intact cephalotane-type C20 diterpenoids, we develop two synthetic routes to explore their syntheses from cephalotane-type C18 dinorditerpenoid-cephanolide B, involving ring expansion/C17-introduction and its reverse process. The first synthetic route is unsuccessful due to the great difficulty of C17-introduction and the first total synthesis cephalotane-type C20 diterpenoid cephanolide E is finally realized via the second synthetic route. [Display omitted] [ABSTRACT FROM AUTHOR]