Synthesis of (–)-probetaenone I: structural confirmation of biosynthetic precursor of betaenone B

Abstract

Probetaenone I (1) has been synthesized by an intramolecular Diels-Alder reaction and, thereby, its structure has been clearly confirmed; in the biosynthesis of betaenone B (2) the stereochemistry of the C-8 hydroxylation of (1) was proved to involve retention of configuration.Paper 9/05458H

Chemistry and Biology of Biosynthetic Diels–Alder Reactions

“…[26] Synthesis of 47 through an intramolecular Diels-Alder reaction confirmed the structure and provided credence for the proposed biosynthetic pathway. [27] Scheme 8. Incorporation of deuterated trienes into solanapyrones A (26) and D (27).…”

“…[27] Scheme 8. Incorporation of deuterated trienes into solanapyrones A (26) and D (27). The thioacetal of 27 is the major product (2:1) in the laboratory synthesis.…”

“…The isolation of the minor metabolite solanapyrone D (27), a diastereomer of 26, provided additional support for the Diels-Alder reaction in the biosynthetic pathway. [17] Rotation about the C5ÀC6 bond in the Diels-Alder reaction could give rise to either the exo-or endo-cycloaddition products (Scheme 8).…”

“…[19,20] Incorporation of the precursor 30 indicated loss of deuterium at C17. The ratio of the integration for the signals of deuterium at C17 to deuterium at C18 in the 2 Enzymatic activity was found in a cell-free extract of Alternaria solani, which catalyzed the conversion of 33 into solanapyrones A (26) and D (27) in 25 % yield with a ratio of the exo to endo cycloadduct of 53:47 . [21] A control experiment with denatured enzyme provided a 3:97 ratio of the exo to endo cycloadducts with only 10 % consumption of starting material.…”

Recent advances of Diels–Alderases involved in natural product biosynthesis

“…19,20 In 2015, we identified a betaenone octaketide synthase (Bet1) and a trans-acting enoyl reductase (Bet3), which participate in the formation of dehydroprobetaenone I (5) having a decalin scaffold by heterologous expression of the corresponding genes (Scheme 3). 21 Chemical reactivity and conformational analysis suggested that involvement of DAase PKS Bet1 at the stage of reductive release of growing polyketide chain giving reactive trienone although non-enzymatic reaction 22 cannot be ruled out.…”