Language
English
Publication Date
5-3-2024
Journal
Organic Letters
DOI
10.1021/acs.orglett.4c00528
PMID
38506470
PMCID
PMC12415967
PubMedCentral® Posted Date
9-9-2025
PubMedCentral® Full Text Version
Post-print
Abstract
The morpholine heterocycle is a structural unit found in many bioactive compounds and FDA-approved drugs, but the generation of more complex C-functionalized morpholine derivatives remains considerably underexplored. Using systematic chemical diversity (SCD), a concept that guides the expansion of saturated drug-like scaffolds through regiochemical and stereochemical variation, we describe the synthesis of a collection of methyl-substituted morpholine acetic acid esters starting from enantiomerically pure amino acids and amino alcohols. In total, 24 diverse substituted morpholines were produced that vary systematically in regiochemistry and stereochemistry (relative and absolute). These diverse C-substituted morpholines can be directly applied in fragment screening or incorporated as building blocks in medicinal chemistry and library synthesis.
Keywords
Morpholines, Molecular Structure, Stereoisomerism, Esters, Amino Acids, Chemistry, Pharmaceutical
Published Open-Access
yes
Recommended Citation
Tang, Sunny Ann; Fults, Afton; Boyd, Shelton R; et al., "Expanding Complex Morpholines Using Systematic Chemical Diversity" (2024). Faculty and Staff Publications. 3877.
https://digitalcommons.library.tmc.edu/baylor_docs/3877
Graphical Abstract