Synthesis of regiospecifically labeled [18O]glycolic acid and [18O]acyldihydroxyacetone phosphate.
Methods are detailed for the preparation of [2-18O]glycolate from chloroacetic acid and for the direct conversion of these intermediates to regiospecifically labeled [2-18O]-2-O-acylglycolic acids containing approximately 90% 18O at the C-O-acyl bond. Methods are also detailed for optimization of reaction conditions and yields for each synthetic step in previously published methods for the preparation of 1-O-acyldihydroxyacetone-3-O-phosphate (DHAP) from acyloxyacetic acid (i.e., 2-O-acylglycolic acid), where acyl is tetradecanoyl, hexadecanoyl, or heptadecanoyl. The optimized reaction conditions generate 1-O-acyl DHAP in its acid form, both in high overall yield and in high purity, without requiring a final chromatographic purification of the product, 1-O-acyl DHAP. Combining these new methods, efficient and facile preparations of regiospecifically labeled [1-18O]-1-O-hexadecanoyl DHAP and [1-18O]-1-O-heptadecanoyl DHAP have now been demonstrated, in which approximately 90% 18O is specifically located only at the C-O-acyl position. Some mechanistic postulates are offered to account for the optimized yields, regioselectivities, and high 18O incorporation which are observed in the reactions we have employed to generate 1-O-acyl DHAP from glycolate intermediates.
Peterson
D M
DM
Department of Medicine, University of Texas Health Science Center, San Antonio.
Martinez
R A
RA
Satsangi
N
N
Weintraub
S T
ST
Stotter
P L
PL
Friedberg
S J
SJ
D004098:Dihydroxyacetone / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D004099:Dihydroxyacetone Phosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D006016:Glycolates / Q000138:chemical synthesis*; D013058:Mass Spectrometry; D010103:Oxygen Isotopes; D014306:Trioses / Q000138:chemical synthesis*
D006016:Glycolates; D010103:Oxygen Isotopes; D014306:Trioses; C031149:glycolic acid; C053176:heptadecanoyl dihydroxyacetone phosphate; C003037:palmitoyl dihydroxyacetone phosphate; D004099:Dihydroxyacetone Phosphate; D004098:Dihydroxyacetone