Research Page

Current Research

Research in the Martin lab focuses on the development of new catalytic transformations, novel strategies for bond activation and the synthesis of bioactive molecules for the study and treatment of human disease. We find inspiration both through the identification of bioactive natural product targets and through consideration of larger problems where organic chemistry is poised to offer practical solutions (e.g. depolymerization and selective functionalization of biomass). Our goal is to provide reaction platforms that are both practical and sustainable and to work with groups specialized in biological and biochemical fields to investigate the causes and prevention of diseases such as cancer and neurodegeneration.

Sustainable Catalysis

Converting abundant, renewable feedstocks into valuable chemical building blocks is an important goal to improve the sustainability of the global chemical enterprise. As we transition from petroleum sources to renewable sources such as plant biomass, the need arises for efficient strategies to manipulate and functionalize highly oxygenated feedstocks such as sugars, lignin and lignocellulose, as well as modify hydroxylated natural products more generally. We are developing novel methods for the reductive functionalization, redox-neutral cross coupling and catalytic deoxygenation of alcohols. We have reported a cobalt-mediated strategy for the carbonylation/decarboxylation of benzylic alcohols (Organometallics 2019). We are investigating this strategy as a photocatalytic method for the activation of C–O bonds in alcohols to allow the efficient formation of alkyl radicals for both deoxygenation and C–C bond formation. We use a variety of light sources to provide visible light irradiation to our reactions, ranging from simple CFL bulbs to LEDs including the high intensity Kessil PR160 series of blue LED lamps. Selecting the right wavelength for each photocatalyst system can improve reaction rates and product yields. This research has been supported by a CAREER grant from the NSF (CHE-1952860).

We are also investigating the use of H-atom transfer (HAT) in activating C–H bonds for functionalization of a variety of hydrocarbons and simple molecules. We have a longstanding interest in the functionalization of diamondoids, rigid caged hydrocarbons that map onto the diamond lattice. We reviewed the direct radical functionalization (C-H to C-C via radicals) of diamondoids in OBC 2022. In 2019, we reported a visible light-mediated method for the direct alkylation of diamondoids such as adamantane and diamantane that proceeds with a unique selectivity profile (ACS Catalysis 2019). The direct substitution of various substituted adamantanes and drug derivatives occurs at the strongest C–H bond in the presence of a variety of common functional groups, including electronically activating N- and O-derivatives. This work was highlighted in 2019 (link) and was more recently expanded to aminoalkylation to access N-substituted derivatives with antiviral properties and the core of saxagliptin, a diabetes drug (ChemComm 2020). More recently, we explored a new mechanism for diamondoid functionalization using highly oxidizing pyrylium photocatalysts (ACS Catalysis 2024). This work featured extensive mechanistic studies (EPR, Stern-Volmer luminescence quencing, cyclic voltammetry) and the functionalization of higher diamondoids such as triamantane and tetramantane. Ongoing research aims to understand the underlying mechanistic principles and develop new strategies for site-selective C–H functionalization reactions. This research is supported by a MIRA grant from the NIH (R35-GM138050).

More recently, we have become interested in the use of iron catalysts for C-H functionalization reactions, with the goal of developing general reactions that use visible light rather than ultraviolet (UV) light. We have discovered a wavelength-selective catalytic reaction that provides new insight into the role of ligand-to-metal-charge transfer (LMCT) in iron catalysis.

Design and Synthesis of Bioactive Molecules

Another major focus of the lab is the exploration of general approaches to families of natural products where promising biological activity has been reported, in particular in the areas of neuroprotection and non-oncogene addiction. We have previously reported a Heck-based strategy for the synthesis of phenolic lipids such as anacardic and ginkgolic acids (OrgLett 2018). In collaboration with Dr. Jeff Perry in the Department of Biochemistry at UCR, we studided their use as inhibitors of both MMP and SUMOylation enzymes. We have also investigated the synthesis of decalin-based terpenes (OrgLett 2018) and revised the structure of an earthworm metabolite through synthesis and NMR techniques in collaboration with the Larive lab (JNatProd 2019). We are eager to collaborate on new projects where our synthesis skills can be leveraged to ask biological questions and gain information on the mechanism of action of bioactive compounds.

We are currently developing synthetic strategies to neuroprotective natural products, such as the limonoids, to provide probe molecules and investigate their mechanism of action. In collaboration with other researchers in the Iowa Neuroscience Institute (INI), including the Doorn Lab, we are testing natural products and small molecule analogs for neuroprotective activity. We have synthesized fraxinellone, calodendrolide, and many unnatural analogs, and have identified simplidied analogs with significantly improved neuroprotective activity against glutamate toxicity and environmental neurotoxins, such as pesticides. The ultimate goal is to provide molecular tools for the investigation of neurodegenerative processes and structure-activity relationship data for the development of neuroprotective small molecules as drugs for the treatment of neurodegenerative disease. This research is supported by a MIRA grant from the NIH (R35-GM138050).