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Modular synthesis of cell-permeating 2-ketoglutarate esters.

ABSTRACT: Cell-permeating esters of 2-ketoglutarate (2-KG) have been synthesized through a convergent sequence from two modules in two and three steps, respectively. This route provides access to a full series of mono- and disubstituted 2-KG esters, enabling us to define the effect of regioisomeric masking on metabolite release and antihypoxic activity in cell-based assays. In addition to providing insight into the biological activity of cell permeable 2-KG esters, the straightforward and modular nature of this synthetic route may prove useful for the development of next-generation 2-KG analogues for diagnostic and therapeutic applications.

SUBMITTER: Zengeya TT

PROVIDER: S-EPMC6320255 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Modular synthesis of cell-permeating 2-ketoglutarate esters.

Zengeya Thomas T TT Kulkarni Rhushikesh A RA Meier Jordan L JL

Organic letters 20150427 10

Cell-permeating esters of 2-ketoglutarate (2-KG) have been synthesized through a convergent sequence from two modules in two and three steps, respectively. This route provides access to a full series of mono- and disubstituted 2-KG esters, enabling us to define the effect of regioisomeric masking on metabolite release and antihypoxic activity in cell-based assays. In addition to providing insight into the biological activity of cell permeable 2-KG esters, the straightforward and modular nature o ...[more]

PMID: 25915096

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