184481-10-5Relevant academic research and scientific papers
Identification, Synthesis, and Characterization of a Major Circulating Human Metabolite of TRPV4 Antagonist GSK2798745
Pero, Joseph E.,McAtee, John J.,Behm, David J.,Briand, Jacques,Graczyk-Millbrandt, Grazyna,Erhard, Karl,Roberts, Andrew D.,Rivero, Ralph A.,Holt, Dennis A.,Lawhorn, Brian G.
supporting information, p. 1498 - 1502 (2021/09/13)
GSK2798745, an antagonist of the transient receptor potential vanilloid 4 (TRPV4) ion channel, was recently investigated in clinical trials for the treatment of cardiac and respiratory diseases. Human plasma and urine samples collected from healthy volunteers following oral administration were analyzed to identify circulating and excreted metabolites of the parent drug. One major circulating metabolite (1) was found in pooled human plasma samples, accounting for approximately half of the observed drug-related material. Isolation of metabolite 1 from urine samples followed by MS and NMR studies led to a putative structural assignment of 1 where hydroxylation of GSK2798745 occurred on the central ring, producing a penta-substituted cyclohexane structure containing three stereocenters. Two unique chemical syntheses of the proposed structure were developed to confirm the identity of metabolite 1 and provide access to gram quantities for biological characterization.
A concise, stereocontrolled total synthesis of rippertenol
Snyder, Scott A.,Wespe, Daniel A.,Von Hof, J. Marian
supporting information; experimental part, p. 8850 - 8853 (2011/08/04)
The first total synthesis of the unique terpene rippertenol, a molecule with dense stereochemical complexity arrayed on a compact framework largely devoid of functional groups, is described. Key elements include orchestrated and unique applications of aldol condensations, Diels-Alder chemistry, and a ring expansion to advance a chiral starting material containing a single chiral center into the final target in a concise and diastereocontrolled manner.
Concise total syntheses of the sesquiterpenoids (-)-homalomenol A and (-)-homalomenol B
Piers, Edward,Oballa, Renata M.
, p. 8439 - 8447 (2007/10/03)
The conjugate additions of the organocopper(I) reagents 22 and 27 to the enantiomerically homogeneous bicyclic enone 4 provided, after epimerization (NaOMe, MeOH) of the resultant product mixtures and appropriate chromatographic separations, the bicyclo[4.3.0]nonan-2-ones 24 and 28. Compounds 24 and 28 were readily converted, via two synthetic steps in each case, into the sesquiterpenoids (-)-homalomenols B (2) and A (1), respectively.
Synthesis of optically active cyclohexenol derivatives via enzyme catalyzed ester hydrolysis of 4-acetoxy-3-methyl-2-cyclohexenone
Polla, Magnus,Frejd, Torbjoern
, p. 5883 - 5894 (2007/10/02)
The optically active cyclohexenol derivatives 9a-9d, and 10a-10c are synthesized from (-)-6, which is obtained by enzymatic ester hydrolysis of racemic 8. Attempts towards the synthesis of the taxane skeleton are described.
