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 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.