The Chemistry of the Defensive Secretions of Three Species of Millipedes in the Genus Brachycybe.

Millipedes have long been known to produce a diverse array of chemical defense agents that deter predation. These compounds, or their precursors, are stored in high concentration within glands (ozadenes) and are released upon disturbance. The subterclass Colobognatha contains four orders of millipedes, all of which are known to produce terpenoid alkaloids-spare the Siphonophorida that produce terpenes. Although these compounds represent some of the most structurally-intriguing millipede-derived natural products, they are the least studied class of millipede defensive secretions. Here, we describe the chemistry of millipede defensive secretions from three species of Brachycybe: Brachycybe producta, Brachycybe petasata, and Brachycybe rosea. Chemical investigations using mass spectrometry-based metabolomics, chemical synthesis, and 2D NMR led to the identification of five alkaloids, three of which are new to the literature. All identified compounds are monoterpene alkaloids with the new compounds representing indolizidine (i.e. hydrogosodesmine) and quinolizidine alkaloids (i.e. homogosodesmine and homo-hydrogosodesmine). The chemical diversity of these compounds tracks the known species phylogeny of this genus, rather than the geographical proximity of the species. The indolizidines and quinolizidines are produced by non-sympatric sister species, B. producta and B. petasata, while deoxybuzonamine is produced by another set of non-sympatric sister species, B. rosea and Brachycybe lecontii. The fidelity between the chemical diversity and phylogeny strongly suggests that millipedes generate these complex defensive agents de novo and begins to provide insights into the evolution of their biochemical pathways.

Branched tyramides from males of the harvester ant, Pogonomyrmex badius.

Tyramides are produced in microgram quantities by males of species in the large Myrmicine ant sub-family (> 7000 species). Tyramides are transferred to female sexuals during mating where a specific female sexual evolved enzyme hydrolyzes the tyramides to the biogenic amine, tyramine. Tyramine is a ligand for receptors that rapidly activate reproductive development in the newly mated queen-previously reproductively inhibited by the mother queen. Without this elaborate biogenic amine precursor and co-evolved female sexual derived tyramide hydrolase, the defenseless newly mated queen's worker production would be delayed by up to 6 days, which could be lethal to the new queen. This is one of possibly several ant species separation mechanisms evolved to maintain species integrity. Here we report two methyl-branched tyramides from harvester ant, Pogonomyrmex badius, males, including one highly branched tyramide not previously reported.

Photoredox/Cobalt Dual-Catalyzed Decarboxylative Elimination of Carboxylic Acids: Development and Mechanistic Insight.

Recently, dual-catalytic strategies towards the decarboxylative elimination of carboxylic acids have gained attention. Our lab previously reported a photoredox/cobaloxime dual catalytic method that allows the synthesis of enamides and enecarbamates directly from N-acyl amino acids and avoids the use of any stoichiometric reagents. Further development, detailed herein, has improved upon this transformation's utility and further experimentation has provided new insights into the reaction mechanism. These new developments and insights are anticipated to aid in the expansion of photoredox/cobalt dual-catalytic systems.

Decarboxylative Acetoxylation of Aliphatic Carboxylic Acids.

Organic molecules bearing acetoxy moieties are important functionalities in natural products, drugs, and agricultural chemicals. Synthesis of such molecules via transition metal-catalyzed C-O bond formation can be achieved in the presence of a carefully chosen directing group to alleviate the challenges associated with regioselectivity. An alternative approach is to use ubiquitous carboxylic acids as starting materials and perform a decarboxylative coupling. Herein, we report conditions for a photocatalytic decarboxylative C-O bond formation reaction that provides rapid and facile access to the corresponding acetoxylated products. Mechanistic investigations suggest that the reaction operates via oxidation of the carboxylate followed by rapid decarboxylation and oxidation by Cu(OAc)2.

Photoinduced Kochi Decarboxylative Elimination for the Synthesis of Enamides and Enecarbamates from N-Acyl Amino Acids.

Decarboxylative elimination of easily accessible N-acyl amino acids to provide enamide and enecarbamate building blocks has been realized through the combination of an organophotoredox catalyst and copper acetate as the terminal oxidant. This operationally simple process utilizes inexpensive and readily available reagents without preactivation of the carboxylic acid. Enamides and enecarbamates are now accessible directly from N-acyl amino acids consequently improving upon the utility of Kochi's oxidative decarboxylation of carboxylic acids.

Photocatalytic Aminodecarboxylation of Carboxylic Acids.

Aminodecarboxylation of unactivated alkyl carboxylic acids has been accomplished utilizing an organic photocatalyst. This operationally simple reaction utilizes readily available carboxylic acids to chemoselectively generate reactive alkyl intermediates that are not accessible via conventional two-electron pathways. The organic radical intermediates are efficiently trapped with electrophilic diazo compounds to provide aminated alkanes.

Organophotoredox/palladium dual catalytic decarboxylative Csp3-Csp3 coupling of carboxylic acids and π-electrophiles.

A dual catalytic decarboxylative allylation and benzylation method for the construction of new C(sp3)-C(sp3) bonds between readily available carboxylic acids and functionally diverse carbonate electrophiles has been developed. The new process is mild, operationally simple, and has greatly improved upon the efficiency and generality of previous methodology. In addition, new insights into the reaction mechanism have been realized and provide further understanding of the harnessed reactivity.