Joel Michael Smith

Research topics

Matched from indexed official interests or NIH project evidence.

• PTSD and Trauma
• Depression

Active NIH awards

• Synthesis of Bioactive Natural Products and Unnatural Congeners

  5R35GM150795-03

  NIGMS · FY 2025 · $367K

  Project Summary/Abstract Alkaloid natural products have had an immense impact on the field of therapeutic medicine, and hold promise for the discovery of new neuropharmacological treatments. One area of proposed research in the Smith Lab concerns the development of new psychoplastogenic compounds based on the psychedelic lysergic acid diethylamide (LSD). Although derivatives of LSD have been explored previously over many decades, derivatives bearing various substitutions on the indole ring of the ergoline scaffold have never been explored. All of these derivatives are currently only accessible through total synthesis, and potentially can serve as therapeutic leads for various neuropsychiatric diseases including Parkinson's disease, PTSD, severe depression, and addiction. Our concise synthetic approach to the scaffold of LSD hinges on the utilization and chemical modification of widely available heterocyclic aromatic precursors. This strategy allows for the exploration of chemical space that would otherwise be inaccessible, however therapeutically enabling. Synthetic inspiration drawn from our route to these LSD analogs has led us to investigate the synthesis of marine macrocyclic diamine alkaloids such as the halicyclamines and the sarains. None of these targets have been synthesized previously. Our modular, yet redox-economic platform for assembling these structurally complex compounds hinges on employing heterocyclic starting materials at higher oxidation levels to efficiently access their congeners with lower redox levels. Innovation in this research direction is mainly strategic, demanding a navigation of synthetic assembly that has not been traversed previously. This will also demand tactical advances in chemistry that will undoubtedly shed light on novel reactivity patterns that will be broadly important within the realm of heterocyclic chemistry.

• Synthesis of Bioactive Natural Products and Unnatural Congeners

  5R35GM150795-02

  NIGMS · FY 2024 · $367K

  Project Summary/Abstract Alkaloid natural products have had an immense impact on the field of therapeutic medicine, and hold promise for the discovery of new neuropharmacological treatments. One area of proposed research in the Smith Lab concerns the development of new psychoplastogenic compounds based on the psychedelic lysergic acid diethylamide (LSD). Although derivatives of LSD have been explored previously over many decades, derivatives bearing various substitutions on the indole ring of the ergoline scaffold have never been explored. All of these derivatives are currently only accessible through total synthesis, and potentially can serve as therapeutic leads for various neuropsychiatric diseases including Parkinson's disease, PTSD, severe depression, and addiction. Our concise synthetic approach to the scaffold of LSD hinges on the utilization and chemical modification of widely available heterocyclic aromatic precursors. This strategy allows for the exploration of chemical space that would otherwise be inaccessible, however therapeutically enabling. Synthetic inspiration drawn from our route to these LSD analogs has led us to investigate the synthesis of marine macrocyclic diamine alkaloids such as the halicyclamines and the sarains. None of these targets have been synthesized previously. Our modular, yet redox-economic platform for assembling these structurally complex compounds hinges on employing heterocyclic starting materials at higher oxidation levels to efficiently access their congeners with lower redox levels. Innovation in this research direction is mainly strategic, demanding a navigation of synthetic assembly that has not been traversed previously. This will also demand tactical advances in chemistry that will undoubtedly shed light on novel reactivity patterns that will be broadly important within the realm of heterocyclic chemistry.

• Synthesis of Bioactive Natural Products and Unnatural Congeners

  1R35GM150795-01

  NIGMS · FY 2023 · $367K

  Project Summary/Abstract Alkaloid natural products have had an immense impact on the field of therapeutic medicine, and hold promise for the discovery of new neuropharmacological treatments. One area of proposed research in the Smith Lab concerns the development of new psychoplastogenic compounds based on the psychedelic lysergic acid diethylamide (LSD). Although derivatives of LSD have been explored previously over many decades, derivatives bearing various substitutions on the indole ring of the ergoline scaffold have never been explored. All of these derivatives are currently only accessible through total synthesis, and potentially can serve as therapeutic leads for various neuropsychiatric diseases including Parkinson's disease, PTSD, severe depression, and addiction. Our concise synthetic approach to the scaffold of LSD hinges on the utilization and chemical modification of widely available heterocyclic aromatic precursors. This strategy allows for the exploration of chemical space that would otherwise be inaccessible, however therapeutically enabling. Synthetic inspiration drawn from our route to these LSD analogs has led us to investigate the synthesis of marine macrocyclic diamine alkaloids such as the halicyclamines and the sarains. None of these targets have been synthesized previously. Our modular, yet redox-economic platform for assembling these structurally complex compounds hinges on employing heterocyclic starting materials at higher oxidation levels to efficiently access their congeners with lower redox levels. Innovation in this research direction is mainly strategic, demanding a navigation of synthetic assembly that has not been traversed previously. This will also demand tactical advances in chemistry that will undoubtedly shed light on novel reactivity patterns that will be broadly important within the realm of heterocyclic chemistry.