Title

Progress Toward the Total Synthesis of Credneramide A and B

Presenter Information

Kathryn O'Neal

Document Type

Oral Presentation

Location

SURC Ballroom C/D

Start Date

15-5-2014

End Date

15-5-2014

Keywords

Neuroscience, Organic synthesis

Abstract

In a chemical synapse, the process of synaptic transmission is as follows: when an action potential reaches the axon terminal, it opens voltage-gated calcium channels, allowing calcium ions to enter the terminal. Calcium causes synaptic vesicles filled with neurotransmitter molecules to fuse with the membrane, releasing their contents into the synaptic cleft. The neurotransmitters diffuse across the synaptic cleft and activate receptors on the postsynaptic neuron. High cytosolic calcium in the axon terminal also triggers mitochondrial calcium uptake, which, in turn, activates mitochondrial energy metabolism to produce ATP to support continuous neurotransmission. Many common antidepressants work to inhibit the calcium oscillations in neurons. Two newly discovered natural products, credneramide A and B, were found to inhibit calcium oscillations in cerebrocortical mouse neurons. Phenethylamine, the parent compound of credneramides, targets dopaminergic neurons, resulting in fewer side effects than antidepressants targeting serotonin. We carried out the known reaction between propargylmagnesium bromide and acrolein to assemble 1-hexen-5-yn-3-ol. Then, we lengthened the backbone of the molecule using a chemical reaction known as a Johnson ortho-ester Claisen rearrangement to afford the compound oct-4-en-7-yne ethanoic acid. After these steps have been successfully completed, we will continue the synthesis further, ending with the crednaramide A and B.

Poster Number

17

Faculty Mentor(s)

Chamberland, Stephen

Additional Mentoring Department

Chemistry

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May 15th, 8:30 AM May 15th, 11:00 AM

Progress Toward the Total Synthesis of Credneramide A and B

SURC Ballroom C/D

In a chemical synapse, the process of synaptic transmission is as follows: when an action potential reaches the axon terminal, it opens voltage-gated calcium channels, allowing calcium ions to enter the terminal. Calcium causes synaptic vesicles filled with neurotransmitter molecules to fuse with the membrane, releasing their contents into the synaptic cleft. The neurotransmitters diffuse across the synaptic cleft and activate receptors on the postsynaptic neuron. High cytosolic calcium in the axon terminal also triggers mitochondrial calcium uptake, which, in turn, activates mitochondrial energy metabolism to produce ATP to support continuous neurotransmission. Many common antidepressants work to inhibit the calcium oscillations in neurons. Two newly discovered natural products, credneramide A and B, were found to inhibit calcium oscillations in cerebrocortical mouse neurons. Phenethylamine, the parent compound of credneramides, targets dopaminergic neurons, resulting in fewer side effects than antidepressants targeting serotonin. We carried out the known reaction between propargylmagnesium bromide and acrolein to assemble 1-hexen-5-yn-3-ol. Then, we lengthened the backbone of the molecule using a chemical reaction known as a Johnson ortho-ester Claisen rearrangement to afford the compound oct-4-en-7-yne ethanoic acid. After these steps have been successfully completed, we will continue the synthesis further, ending with the crednaramide A and B.