Phosphonic acid analogs of GABA through reductive dealkylation of phosphonic diesters with lithium trialkylborohydrides

Journal Article · Mon Jan 01 00:00:00 EST 2007 · Bioorganic & Medicinal Chemistry Letters

DOI:https://doi.org/10.1016/j.bmcl.2007.04.026· OSTI ID:930910

Chowdhury, Sarwat ^[1]; Muni, Niraj J. ^[1]; Greenwood, Nicholas P. ^[1]; Pepperberg, Dr. David R. ^[1]; Standaert, Robert F ^[2]

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1. University of Illinois, Chicago
2. ORNL

Lithium trialkylborohydrides were found to effect rapid monodealkylation of phosphonic diesters, and this reaction was applied to the synthesis of alkylphosphonic acid 2-aminoethyl esters [H2N(CH2)2OP(OH)R, 4], a little-explored class of analogs of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Compound 4a (R = Me) proved to be a potent antagonist at human ρ1 GABAC receptors (expressed in Xenopus laevis oocytes), with an IC50 of 11.1 M, but is inactive at α1β2γ2 GABAA receptors.

• Research Organization: Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
• Sponsoring Organization: USDOE Laboratory Directed Research and Development (LDRD) Program
• DOE Contract Number: DE-AC05-00OR22725
• OSTI ID: 930910
• Journal Information: Bioorganic & Medicinal Chemistry Letters, Vol. 17, Issue 13
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
DEALKYLATION
LITHIUM COMPOUNDS
CATALYTIC EFFECTS
OOCYTES
PHOSPHONIC ACID ESTERS
SYNTHESIS
NERVE CELLS
RECEPTORS
GABA antagonists
GABAC receptors
dealkylation
phosphonate estes
lithium trialkylborohydrides