Origins of Selectivity in Pericyclic Reaction Cascades for the Synthesis of Gambogin and Lateriflorone

Abstract

[reaction: see text] Quantum mechanical calculations demonstrate that the second step of a Claisen-Diels-Alder reaction cascade controls regioselectivity that gives advanced intermediates for the synthesis of gambogin and 1-O-methyllateriflorone.

Polyprenylated Phloroglucinols and Xanthones

“…The concurrent acceleration of the Diels-Alder component of this cascade may be due to the hydrophobic effect of water [125] rather than to a polarity or hydrogen-bonding phenomena [126][127][128]. Computational studies on the above-mentioned reaction have also concluded that the Claisen rearrangement is reversible and the energetics of the irreversible Diels-Alder cyclization can determine the product formation [129]. [115] for the synthesis of 6-O-methylforbesione (147c).…”

“…It has been proposed that the unprecedented spiroxalactone motif of lateriflorone (129) relevant hypothesis could involve conversion of xanthone (172) into dioxepanone (171) that, upon hydrolysis and spirocyclization at the C16 center, could form the spiroxalactone ring system of lateriflorone.…”

“…For instance, 6-O-methylneobractatin (128) is the only natural product known to contain a modified caged scaffold, referred to as the neo-motif [84,85]. In addition, in the structure of lateriflorone (129) [86], the caged motif is attached to a spiroxalactone core, which is likely a product of oxidation of the xanthone B ring.…”

Caged Garcinia Xanthones: Development Since 1937

“…The Claisen reaction was regarded as nonregioselective due to concomitant allylation at both C-5 and C-6 centers [4,5,[94][95][96][97], creating intermediates 100 and 101, respectively [93]. These intermediates then generated an isomeric mixture of 102 and 103, representing the regular caged scaffold, and the so-called neo scaffold, respectively [4,5,[94][95][96][97].…”

“…Quantum mechanical calculations demonstrated that the Claisen rearrangement is reversible and relatively unselective, while the Diels-Alder reaction determins the product ratio and favors the formation of the five-membered ring [96]. It was proposed that differences in resonance stabilization of the oxygen and the carbonyl groups of the products could lead to selectivity [103].…”