Date of Award
12-2025
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
School
Mathematics and Natural Sciences
Committee Chair
Dr. Douglas Masterson
Committee Chair School
Mathematics and Natural Sciences
Committee Member 2
Dr. Julie Pigza
Committee Member 2 School
Mathematics and Natural Sciences
Committee Member 3
Dr. Karl Wallace
Committee Member 3 School
Mathematics and Natural Sciences
Committee Member 4
Dr. Wujian Miao
Committee Member 4 School
Mathematics and Natural Sciences
Committee Member 5
Dr. Robert J Hondal
Abstract
The “Malonate Template” provides access to various amino acids, all from a common intermediate. Herein, demonstrates the use of the malonate template to establish a synthetic route to both 2-thiohistidine and 2-thio-3-N-methyl-histidine from a benzyl methyl malonate derived intermediate. Furthermore, efforts exploiting the applicability of the malonate template for the of both 2-thiohistidine and 2-thio-3-N-methyl-histidine as a suitable alternative to methods previously described by Erdelmeier are described.
The method presented incorporates modifications to the biomimetic pathway described by Erdelmeier for the synthesis of 2-thiohisidine. By exploiting the biomimetic formation of 2-thiohisitidne’s mechanism via mass spectrometry, we demonstrated that 2-thiohsitidine is a by-product of a β-elimination of DHA from the cysteine adduct proposed by Erdelmeier. Accordingly, we were able to incorporate the pathway into our malonate template for a more efficient and versatile synthesis of both 2-thiohsitidne and 2-thio-3-N-methyl-histidine.
Furthermore, with many enantioenriched novel amino acids synthesized previously from the malonate template, we sought to develop a method for rapidly assessing the optical purity of the malonate derived novel amino acids using a deuterium labeled probe for quantifying optical purity directly from 1H-NMR. Our results or consistent with those demonstrated by HPLC and carbon-13 labeling from assaying PLE and six iso-enzymes.
ORCID ID
0000-0002-0576-4005
Copyright
Thomas Owens, 2025
Recommended Citation
Owens, Thomas, "The Malonate Template: The Key to Unlocking Novel Amino Acids" (2025). Dissertations. 2417.
https://aquila.usm.edu/dissertations/2417