Total Synthesis of (−)-Solanapyrone A via Enzymatic Diels−Alder Reaction of Prosolanapyrone

Abstract

The syntheses of prosolanapyrones I (6) and II (7) via the aldol reactions of pyrone and dienal segments have been achieved in five steps in 31% overall yield for 6 and seven steps in 5% overall yield for 7. An improved synthetic route starting from vinylpyrone 27 provided 7 in 11 steps in 12% overall yield. The enzymatic Diels−Alder reaction of 7 affords (−)-solanapyrone A (1) with high enantioselectivity and with good exo-selectivity, which is difficult to attain by chemical methods. In addition, a crude enzyme preparation from Alternaria solani has been used to perform a kinetic resolution of (±)-3.

The Diels–Alderase Never Ending Story

“…In aqueous medium, the non-enzymatic reactions of 12-14 were accelerated and gave endo-adducts with high selectivity (15 : 16 = 3 : 97) [28]. These effects were observed significantly in the reaction of 14 but not in that of 13, indicating that the oxidation of 13 significantly enhanced the reactivity for the Diels-Alder reaction.…”

“…To assess the diastereoselectivity and the intrinsic reactivity of prosolanapyrones, Diels-Alder reactions were examined under various conditions [28]. In less polar solvents, heating was required for the effective cycloaddition of 12 to 14.…”

Six‐Membered Rings with One Oxygen: Pyrylium Ion, Related Systems and Benzo‐Derivatives

“…In this sense, 2H-pyran-2-ones bearing a hydroxy or alkoxy group at C4 have been described as useful intermediates for accessing natural compounds with the skeleton of 4-hydroxy-3-substituted-2-pyranones [109]. Scheme 18.65 shows the reaction of the 4-methoxy-2-pyranone (210) with an electrophile, in the presence of titanium tetrachloride, to give the 3-formylpyranone 211 [110].…”

Biomimetic Synthesis of Non‐Aromatic Polycyclic Polyketides

“…The exo cycloadduct corresponds to the cis-decalin ring of solanapyrones A and B, while the endo cycloadduct holds the trans-fusion of solanapyrones D and E. The first biomimetic synthesis of (±)-solanapyrone A (23) and coworkers that thermal conditions and A. solani cell-free extracts promoted different stereoselectivity. The same team succeeded in the enantioselective and exo-selective synthesis of (−)-23 utilizing a crude enzyme preparation [31]. Recently, the purification and identification of the Diels-Alderase solanapyrone synthase has been achieved [32].…”