Synthetic Strategies toward Natural Products Containing Contiguous Stereogenic Quaternary Carbon Atoms

Abstract

Strategies for the total synthesis of complex natural products that contain two or more contiguous stereogenic quarternary carbon atoms in their intricate structures are reviewed with twelve representative examples. Emphasis has been put on the methods to create quarternary carbon stereocenters, including syntheses of the same natural product from different groups, thereby showcasing diversity of thought and individual creativity. A compendium of selected natural products containing two or more contiguous stereogenic quarternary carbon atoms and key reactions in their total or partial syntheses is provided in the Supporting Information section.

Acyclic Quaternary Carbon Stereocenters via Enantioselective Transition Metal Catalysis

“…This method was used to construct oxetanes 90 and cyclopropanes 91 bearing quaternary carbon stereocenters, as well as the terpenoid natural products oridamycin A, triptoquinones B and C and isoiresin (not shown), 92 which incorporate vicinal quaternary carbon stereocenters. 93, 94 …”

Concise Synthesis of (−)-Hodgkinsine, (−)-Calycosidine, (−)-Hodgkinsine B, (−)-Quadrigemine C, and (−)-Psycholeine via Convergent and Directed Modular Assembly of Cyclotryptamines

“…1 A subset of these natural products, alkaloids comprised of multiple cyclotryptamine units, presents a considerable synthetic challenge due to the presence of multiple quaternary stereocenters as well as numerous basic nitrogen atoms (Figure 1). While there have been significant advances in catalyst- and substrate-controlled formation of C sp2 –C sp3 2,3 and C sp3 –C sp3 4,5,6,7 quaternary stereocenters in the context of cyclotryptamine alkaloids, 8 the synthesis of oligocyclotryptamines remains a challenge due to the paucity of methods allowing for precise introduction of all quaternary stereocenters.…”

P450-Mediated Coupling of Indole Fragments To Forge Communesin and Unnatural Isomers

“…1 A defining feature of these natural products is the presence of vicinal quaternary carbon stereocenters, which are particularly intriguing from both synthetic and biosynthetic perspectives. 2 Synthetic approaches to the vicinal quaternary stereocenters of these natural products have been developed and include Heck cyclization methodology, bis(alkylation) chemistry, pericyclic reactions, and radical couplings. 2 The biosynthetic pathways to these natural products, however, have been much less well-studied and the enzymes responsible for vicinal quaternary stereocenter formation have not been revealed.…”

“…2 Synthetic approaches to the vicinal quaternary stereocenters of these natural products have been developed and include Heck cyclization methodology, bis(alkylation) chemistry, pericyclic reactions, and radical couplings. 2 The biosynthetic pathways to these natural products, however, have been much less well-studied and the enzymes responsible for vicinal quaternary stereocenter formation have not been revealed. Identifying the biocatalysts that form the C3-C3′ linkage is an important objective towards better understanding of indole dimer biosynthesis and how Nature can efficiently construct complex scaffolds.…”