Los Alamos National Security, LLC

University of California

Marc A Alvarez

Rodolfo Antonio Martinez

Clifford J Unkefer

Louis A Silks

Jurgen G Schmidt

Robert F Williams

David Bryan Kimball

Rudolfo A Martinez

Compounds having stable isotopesC and/orH were synthesized from precursor compositions having solid phase supports or affinity tags.

Isotopically labeled compositions and method

The present invention is directed to the labeled compounds, wherein C* is each eitherC andC where at least one C* isC, each hydrogen of the methylene group is hydrogen or deuterium, the methyl group includes either zero or three deuterium atoms, Q is sulfide, sulfinyl, or sulfone, Z is an aryl group such as 1-naphthyl, substituted 1-naphthyl, 2-naphthyl, substituted 2-naphthyl, or a phenyl group wherein R, R, R, Rand Rare each independently either hydrogen, a C-Clower alkyl, a halogen, and an amino group such as NH, NHR and NRR' where R and R&#x2032; are each independently either a C-Clower alkyl, a phenyl, and an alkoxy group, and the methyl group can include either zero or three deuterium atoms. The present invention is also directed to the labeled compounds 

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The present invention is directed to labeled compounds of the formulae  wherein R, R, R, Rand Rare each independently selected from the group consisting of hydrogen, a C-Clower alkyl, a halogen, and an amino group selected from the group consisting of NH, NHR and NRR' where R and R&#x2032; are each independently selected from the group consisting of a C-Clower alkyl, an aryl, and an alkoxy group, and X is selected from the group consisting of hydrogen, a C-Clower alkyl group, and a fully-deuterated C-Clower alkyl group.

The present invention is directed to labeled compounds, of the formulae wherein C* is each independently selected from the group consisting ofC andC with the proviso that at least one C* isC, each hydrogen of the methylene group can independently be either hydrogen or deuterium, the methyl group includes either zero or three deuterium atoms, Q is from the group of sulfide, sulfinyl, and sulfone, Z is an aryl group from the group of 1-naphthyl, substituted 1-naphthyl, 2-naphthyl, substituted 2-naphthyl, and phenyl groups with the structure wherein R, R, R, Rand Rare each independently from the group of hydrogen, a C-Clower alkyl, a halogen, and an amino group from the group of NH, NHR and NRR' where R and R&#x2032; are each independently from the group of a C-Clower alkyl, a phenyl, and an alkoxy group, and the methyl group can include either zero or three deuterium atoms.

The present invention is directed to labeled compounds of the formulae  wherein R, R, R, Rand Rare each independently selected from the group consisting of hydrogen, a C-Clower alkyl, a halogen, and an amino group selected from the group consisting of NH, NHR and NRR' where R and R&#x2032; are each independently selected from the group consisting of a C-Clower alkyl, an aryl, and an alkoxy group, and X is selected from the group consisting of hydrogen, a C-Clower alkyl group, and a fully-deuterated C-Clower alkyl group. The present invention is also directed to a process of preparing labeled compounds, e.g., process of preparing [C]methacrylic acid by reacting a (CHCHO&#x2014;C(O)&#x2014;CH)&#x2014; aryl sulfone precursor withCHI to form a (CHCHO&#x2014;C(O)&#x2014;C(CH))&#x2014; aryl sulfone intermediate, and, reacting the (CHCHO&#x2014;C(O)&#x2014;C(CH))&#x2014; aryl sulfone intermediate with sodium hydroxide, followed by acid to form [C]methacrylic acid. The present invention is further directed to a process of preparing [H]methyl methacrylate by reacting a (HOOC&#x2014;C(CH)&#x2014; aryl sulfinyl intermediate with CDI to form a (HCOOC&#x2014;C(CH))&#x2014; aryl sulfinyl intermediate, and heating the(HCOOC&#x2014;C(CH))&#x2014; aryl sulfinyl intermediate at temperatures and for time sufficient to form [H]methyl methacrylate.

The present invention is directed to asymmetric chiral labeled glycerols including at least one chiral atom, from one to twoC atoms and from zero to four deuterium atoms bonded directly to a carbon atom, e.g., (2S) [1,2-C]glycerol and (2R) [1,2-C]glycerol, and to the use of such chiral glycerols in the preparation of labeled amino acids.

Synthesis of &lsqb;2H1, 13C&rsqb;, &lsqb;2H2, 13C&rsqb; and &lsqb;2H3, 13C&rsqb;methyl aryl sulfones and sulfoxides

Synthesis of labeled oxalic acid derivatives

The present invention is directed to labeled compounds, &lsqb;2- C&rsqb;dithane wherein the C atom is directly bonded to one or two deuterium atoms. The present invention is also directed to processes of preparing &lsqb;2- C&rsqb;dithane wherein the C atom is directly bonded to one or two deuterium atoms. The present invention is also directed to labeled compounds, e.g., &lsqb; H , C&rsqb;methanol (arylthio)-, acetates wherein the C atom is directly bonded to exactly one or two deuterium atoms.

Synthesis of 2H- and 13C- substituted compounds

Synthesis of &lsqb;2H1, 13C&rsqb;, &lsqb;2H2, 13C&rsqb; and &lsqb;2H3, 13C&rsqb;methyl aryl sulfides

The present invention is directed to labeled compounds, &lsqb;2- C&rsqb;dithiane wherein the C atom is directly bonded to one or two deuterium atoms. The present invention is also directed to processes of preparing &lsqb;2- C&rsqb;dithiane wherein the C atom is directly bonded to one or two deuterium atoms. The present invention is also directed to labeled compounds, e.g., &lsqb; H , C&rsqb;methanol (arylthio)-, acetates wherein the C atom is directly bonded to exactly one or two deuterium atoms.

Growing community of inventors

Santa Fe, NM, United States of America

Marc A Alvarez