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Divergent Stereoselectivity in Phosphothreonine (pThr)-Catalyzed Reductive Aminations of 3-Amidocyclohexanones.

ABSTRACT: Phosphothreonine (pThr)-embedded peptide catalysts are found to mediate the reductive amination of 3-amidocyclohexanones with divergent selectivity. The choice of peptide sequence can be used to alter the diastereoselectivity to favor either the cis-product or trans-product, which are obtained in up to 93:7 er. NMR studies and DFT calculations are reported and indicate that both pathways rely on secondary interactions between substrate and catalyst to achieve selectivity. Furthermore, catalysts appear to accomplish a parallel kinetic resolution of the substrates. The facility for phosphopeptides to tune reactivity and access multiple products in reductive aminations may translate to the diversification of complex substrates, such as natural products, at numerous reactive sites.

SUBMITTER: Shugrue CR

PROVIDER: S-EPMC5963540 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Divergent Stereoselectivity in Phosphothreonine (pThr)-Catalyzed Reductive Aminations of 3-Amidocyclohexanones.

Shugrue Christopher R CR Featherston Aaron L AL Lackner Rachel M RM Lin Angela A Miller Scott J SJ

The Journal of organic chemistry 20180405 8

Phosphothreonine (pThr)-embedded peptide catalysts are found to mediate the reductive amination of 3-amidocyclohexanones with divergent selectivity. The choice of peptide sequence can be used to alter the diastereoselectivity to favor either the cis-product or trans-product, which are obtained in up to 93:7 er. NMR studies and DFT calculations are reported and indicate that both pathways rely on secondary interactions between substrate and catalyst to achieve selectivity. Furthermore, catalysts ...[more]

PMID: 29547285

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