Total synthesis of cyrneines A–B and glaucopine C

Abstract

The cyrneine diterpenoids represent a structurally intriguing subfamily of cyathane diterpenoids and could significantly induce neurite outgrowth. Therefore, the efficient synthesis of these natural products is of great importance. Herein, we present a route for the collective synthesis of cyrneines A, B, and glaucopine C. As the key precursor, the 5-6-6-tricyclic scaffold is efficiently constructed by employing a mild Suzuki coupling of heavily substituted nonactivated cyclopentenyl triflate and a chelation-controlled regiospecific Friedel-Crafts cyclization as key transformations. The stereoselective installation of the all-carbon quaternary center at C6 ring junction of the tricycle is achieved via Birch reductive methylation. Subsequently, a carbenoid-mediated ring expansion furnishes the essential 5-6-7-tricyclic core. Finally, manipulation of this core by several appropriately orchestrated conversions accomplishes a more step-economic synthesis of cyrneine A (20 steps), and the first synthesis of cyrneine B (24 steps) and glaucopine C (23 steps).

Pd-Catalyzed Aerobic Oxidative Heck Cross-Coupling for the Straightforward Construction of Indole δ-Lactams

“…Accordingly, we shifted our focus to a phosphinamide-based palladacycle catalyst 16, which was developed previously by our group (Du et al., 2015, Guan et al., 2014). A supportive clue, albeit not tightly related with the proposed Heck-type reaction, that encouraged us to inspect this catalyst herein is that 16 exhibited extremely high catalytic activity for mild Suzuki coupling of a broad range of arene ( pseudo )halides (Wu et al., 2015, Wu et al., 2018, Cao et al., 2018). To our delight, the use of 16 as catalyst did improve substantially the yield of 15a to 72% (entry 4).…”

Synthesis and Biological Evaluation of Diversified Hamigeran B Analogs as Neuroinflammatory Inhibitors and Neurite Outgrowth Stimulators

“…To the best of our knowledge, this synthetic route represents The synthetic route for the synthesis of 1-hydroxyl-9-epi-hamigeran B intermediate is illustrated in Scheme 2. The synthesis of intermediate diol 9p, began with the known chiral cyclopentaneone 11 as the previous study [28]. Using imidazole and TBSCl to treat compound 11 afforded the α-hydroxy protected compound 12.…”

Synthetic Studies on Enantioselective Total Synthesis of Cyathane Diterpenoids: Cyrneines A and B, Glaucopine C, and (+)-Allocyathin B2

“…Very recently, we successfully developed a route that could be used for a collective total synthesis of cyrneines A ( 1 ) and B ( 2 ), and glaucopine C ( 3 ) . As illustrated in Figure , the pivotal transformations involved in our synthetic route were (i) an enzyme-catalyzed desymmetric enantioselective reduction of the readily available diketone 8 for preparing the chiral starting material 9 in excellent enantioselectivity (99% ee) and diastereoselectivity (ca.…”