Ring scission of diastereomeric 4-butylspiropentylcarbinyl radicals as a chemical model for identifying enzyme-catalyzed FAD adducts resulting from spiropentylacetyl-CoA.
Both diastereomeric 4-butylspiropentylcarbinyl bromides (14a and 14b) were synthesized in seven steps starting from 1-heptyne, and the stereochemical assignments based upon NOE experiments were confirmed by converting their immediate alcohol precursors (13a and 13b) to 1,4-dibutylspiropentanes (17a and 17b) with C(1) and C(2) symmetry. Each bromide was used to generate its corresponding spiropentylcarbinyl radical (18a and 18b) via its AIBN-initiated tri-n-butyltin hydride reduction. The radical-trapped products are identified, the preferred ring scission mode is identified (C1[bond] C2 bond cleavage), and the estimated rates for the ring opening of 4-butylspiropentylcarbinyl radical (18, k(25) degrees C > or = approximately 5 x 10(9) s(-1)) and 2-butyl-1-vinylcyclopropylcarbinyl radical (33, k(25) degrees C approximately 5 x 10(8) s(-1)) are reported. High-level ab initio calculations addressing the ring-opening isomerizations of cyclopropylcarbinyl and spiropentylcarbinyl radicals also are presented. These results in conjunction with a previous study enable us to propose two structures for the enzyme-catalyzed FAD adducts resulting from spiropentylacetic acid-CoA, a synthetic byproduct of fatty acid metabolism.
Lis
Lev
L
Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Koltun
Elena S
ES
Liu
Hung-wen
HW
Kass
Steven R
SR
D003065:Coenzyme A / Q000737:chemistry* / Q000378:metabolism; D005182:Flavin-Adenine Dinucleotide / Q000737:chemistry* / Q000378:metabolism; D005609:Free Radicals / Q000737:chemistry; D008956:Models, Chemical; D018716:Molecular Mimicry; D009690:Nucleic Acid Conformation; D013141:Spiro Compounds / Q000737:chemistry* / Q000378:metabolism
C452223:4-butylspiropentylcarbinyl bromide; D005609:Free Radicals; D013141:Spiro Compounds; C071537:spiropentaneacetic acid; D005182:Flavin-Adenine Dinucleotide; D003065:Coenzyme A