Unified synthesis of caged Garcinia natural products based on a site-selective Claisen/Diels–Alder/Claisen rearrangement

Abstract

A unified synthetic strategy toward caged Garcinia natural products has been designed and implemented. Central to the strategy is a tandem Claisen͞Diels-Alder͞Claisen rearrangement of a suitably substituted xanthone precursor to form forbesione (1a). Serving as a template, forbesione is then used to deliver representative members of this family, including desoxygaudichaudione A (4), desoxymorellin (5), and gambogin (10). Studies on the timing of this reaction cascade suggest that the C-ring Claisen͞Diels-Alder rearrangement proceeds initially and is followed by the A-ring Claisen reaction. The electronic and steric effects that govern the outcome of this cascade are presented.

Polyprenylated Phloroglucinols and Xanthones

“…Similar observations have been reported more recently by other groups [117]. The above-described results towards the synthesis of forbesione along with the results from several model studies [118] can be summarized as follows:…”

Prenylated caged xanthones: Chemistry and biology

“…The Claisen rearrangement was not regioselective, allylation can occur at both C5 and C6 to give two intermediates which subsequently generated two different caged scaffold products (Thoison et al, 2000). The proposal was substantiated about 30 years later by biomimetic synthetic studies by Nicolaou and Li (2001), and Theodorakis and coworkers (Tisdale et al, 2004).…”

Gambogic acid identifies an isoform-specific druggable pocket in the middle domain of Hsp90β

“…GBA (43), Bio-GBA (58), and MAD28 (52)(53)(54)59) were synthesized as previously described. Cell Lines and Transfection.…”