American Chemical Society
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Ring Scission of Diastereomeric 4-Butylspiropentylcarbinyl Radicals as a Chemical Model for Identifying Enzyme-Catalyzed FAD Adducts Resulting from Spiropentylacetyl-CoA

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journal contribution
posted on 2002-01-22, 00:00 authored by Lev Lis, Elena S. Koltun, Hung-wen Liu, Steven R. Kass
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 C1 and C2 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−C2 bond cleavage), and the estimated rates for the ring opening of 4-butylspiropentylcarbinyl radical (18, k25 °C ≥ ∼5 × 109 s-1) and 2-butyl-1-vinylcyclopropylcarbinyl radical (33, k25 °C ∼ 5 × 108 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.