Total Synthesis of Puberuline C

Abstract

Puberuline C (1) is an architecturally complex C19-diterpenoid alkaloid with a unique ring fusion pattern. The 6/7/5/6/6/6-membered rings (ABCDEF-rings) contain one tertiary amine and six oxygen functionalities, and possess 12 contiguously aligned stereocenters, three of which are quaternary. These structural features of 1 make its chemical construction exceptionally challenging. Here, we disclose the first total synthesis of 1. The synthesis was accomplished from 2-cyclohexenone (9) by integrating radical cascade and Mukaiyama aldol reactions as the key transformations. A double Mannich reaction fused the A- and E-rings, and Sonogashira coupling attached the C-ring, efficiently leading to ACE-rings with the requisite 19 carbons of 1. The chemically stable tertiary chloride of the ACE-ring structure was then transformed to the corresponding bridgehead radical, which participated in the simultaneous cyclization of the B- and F-rings via a highly organized radical cascade process. This unusual step installed five contiguous stereocenters, including two quaternary carbons, without damaging the preexisting multiple polar functionalities. Subsequently, the intramolecular Mukaiyama aldol reaction between silyl enol ether and acetal was realized by applying a combination of SnCl4 and ZnCl2, forging the last remaining D-ring of the hexacycle. Finally, 3 was elaborated into 1 through regio- and stereoselective functionalizations of the BCD-rings. Our novel radical-based strategy achieved the total synthesis of 1 in 32 total steps from simple 9, demonstrating the power of the radical cascade reaction to streamline the assembly of highly complex molecules.

Integrated Transcriptomic and Metabolomic Analysis Reveal the Dynamic Process of Bama Hemp Seed Development and the Accumulation Mechanism of α-Linolenic Acid and Linoleic Acid

“…Regarding amino acid metabolism, the KEGG pathways included cysteine and methionine metabolism, amino sugar and nucleotide sugar metabolism (KO:00520), leucine and isoleucine degradation (KO:00280), and tyrosine metabolism. In addition, diterpenoid biosynthesis (KO:00908) was identified in all six comparison groups, which is an important secondary metabolite in plants and possesses significant medical potential as an alkaloid . Moreover, genes related to fatty acid metabolism were found in all six comparison groups, particularly enriched in the following pathways: steroid hormone biosynthesis (KO:00140), LA metabolism (KO:00591), cutin and suberin metabolism (KO:00073), and fatty acid biosynthesis (KO:00061).…”

“…In addition, diterpenoid biosynthesis (KO:00908) was identified in all six comparison groups, which is an important secondary metabolite in plants and possesses significant medical potential as an alkaloid. 37 Moreover, genes related to fatty acid metabolism were found in all six comparison groups, particularly enriched in the following pathways: steroid hormone biosynthesis (KO:00140), LA metabolism (KO:00591), cutin and suberin metabolism (KO:00073), and fatty acid biosynthesis (KO:00061). Notably, LA metabolism (KO:00591) was enriched in all four comparison groups (Figure 7).…”

Metal-free synthesis of carbamoylated dihydroquinolinones via cascade radical annulation of cinnamamides with oxamic acids

“…Radical cascade cyclization is a powerful tool for the streamlined construction of complex molecular frameworks in step- and atom-economical ways. 8 Cascade reactions have the potential to minimize waste and reduce the costs of the process, supporting green and sustainable chemistry. The decarboxylative radical cascade cyclization strategy has been used extensively for the efficient synthesis of N-heterocycles.…”

Continuous Enantioselective α-Alkylation of Ketones via Direct Photoexcitation

“…The α-alkylation of aldehydes and ketones is among the most crucial carbon–carbon bond-forming reactions in organic chemistry and indispensable for synthesizing numerous biologically active compounds and natural products. − In many cases, stereocontrol is needed to force the formation of one defined product. Significant efforts have been made to develop enantioselective methods, primarily relying on chiral auxiliaries .…”