Programmable meroterpene synthesis

Abstract

The bicyclo[3.3.1]nonane architecture is a privileged structural motif found in over 1000 natural products with relevance to neurodegenerative disease, bacterial and parasitic infection, and cancer among others. Despite disparate biosynthetic machinery, alkaloid, terpene, and polyketide-producing organisms have all evolved pathways to incorporate this carbocyclic ring system. Natural products of mixed polyketide/terpenoid origins (meroterpenes) are a particularly rich and important source of biologically active bicyclo[3.3.1]nonane-containing molecules. Herein we detail a fully synthetic strategy toward this broad family of targets based on an abiotic annulation/rearrangement strategy resulting in a 10-step total synthesis of garsubellin A, an enhancer of choline acetyltransferase and member of the large family of polycyclic polyprenylated acylphloroglucinols. This work solidifies a strategy for making multiple, diverse meroterpene chemotypes in a programmable assembly process involving a minimal number of chemical transformations.

The search for, and chemistry and mechanism of, neurotrophic natural products

“…In the course of chemical studies on PPAPs of Garcinia subelliptica (Guttiferae) [ 128 , 129 ], we found that garsubellin A ( 71 ) could increase the ChAT activity, a key enzyme for physiologic acetylcholine synthesis in the nervous system, by up to 154% at 10 μM in comparison with the control in primary cultured P10 rat septal neurons [ 130 ]. Owing to its important biological activity and architectural structure, garsubellin A ( 71 ) stimulated substantial synthetic effort, and the excellent synthetic achievements have been reported [ 127 , 131 – 133 ]. More efficient synthetic methods of 71 , however, still have to be developed to supply sufficient quantities to explore its full biological characterization (Figs.…”

The pinene scaffold: its occurrence, chemistry, synthetic utility, and pharmacological importance

“…Phloroglucin-like natural products such as hyperforin ( Fig. 17 ), berkeleyone A, berkeleydione, huperzine, upia, mexicanolide, rugulosone, nemorosome, and garsubellin A, C, and D 99 have potential medicinal application in treating inflammation, depression, as well as neurologic disorders such as Alzheimer's disease.…”

Progress in neutron techniques: towards improved polymer electrolyte membranes for energy devices

“…From a practical point of view, in complex systems such as hydrated membranes, the scattering function is given by a few terms associated with the polymer (S P ) and water (S W ) dynamics, so that the scattering function can be expressed as: (10) .…”

“…Critical issues that are currently being investigated address improvements in durability and performance efficiency combined with lowered production costs [5,6]. Research to develop and model the chemistry and improve the performance of novel as well as current membrane formulations is under way in laboratories worldwide [6][7][8][9][10]. Neutron scattering (NS) and imaging techniques designed to probe the structure and dynamics of bulk and thin film materials are playing an increasing role in studies to understand, control and develop critical issues of water uptake and management related to polymer structure, selective transport of ions and molecular species through the membrane, and the coupling between these dynamic processes.…”