Biomimetic total synthesis of forbesione and desoxymorellin utilizing a tandem Claisen/Diels–Alder/Claisen rearrangement

Abstract

A concise synthesis of forbesione (1) and desoxymorellin (3) is presented. Central to the strategy is a biomimetic Claisen/Diels-Alder/Claisen reaction cascade that proceeds in a regioselective manner and produces the desired scaffold exclusively. The observed regioselectivity and product distribution of the Claisen/Diels-Alder/Claisen reaction are attributed to the electronic effects of the xanthone oxygen (O10), the C9 carbonyl group and the nature of the C1 functionality.

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

“…The most efficient proved to be a two-step procedure that involved propargylation of the more reactive C3, C5, and C6 phenols with 2-chloro-2-methylbutyne (21) in the presence of KI and K 2 CO 3 under CuI catalysis (25% yield) (23), followed by Lindlar reduction of the pendant alkynes (75% yield) (24). Drawing on previous experience with related structures (25,26), we heated 17a in DMF at 120°C and obtained a mixture of forbesione (1a) (49% yield) and isoforbesione (22a) (35% yield) (18).…”

“…Phloroglucinol (19) and 2,3,4-trihydroxybenzoic acid (20) were commercially available and used without any additional purification. Compounds 1a, 1b, 1c, 17a, 17b, 17c, 22a, 23c, and 5 were synthesized as described previously (18). Full experimental details and analytical and spectroscopic information for all synthetic compounds are provided in supporting information, which is published on the PNAS web site.…”

“…Herein we present a biomimetic synthesis of forbesione (1a) by using a site-selective Claisen͞ Diels-Alder͞Claisen reaction cascade (18). Using forbesione as a base structure, we also report a unified synthetic approach to several other members of this family, including deoxygaudichaudione A (4), desoxymorellin (5), and gambogin (10).…”

Synthesis and Anti‐tumor Evaluation of B‐ring Modified Caged Xanthone Analogues of Gambogic Acid

“…Further reduction of the alkynyl groups using Lindlar catalyst led to the precursors 12a-12d. Subsequently, application of the expected Claisen/Diels-Alder cascade reaction by heating 12a-12c in DMF [24][25][26][27] furnished caged xanthones 13a -13c, respectively, while 12d afforded forbesione (13d) and isoforbesione (13e) as isomers.…”

Analysis of caged xanthones from the resin of Garcinia hanburyi using ultra-performance liquid chromatography/electrospray ionization quadrupole time-of-flight tandem mass spectrometry

“…In China, the clinical trials to evaluate the efficacy and safety of GA have been carried out since the 1970s. Interest in these caged Garcinia xanthones has attracted many attempts to synthesize it using Claisen/Diels-Alder/Claisen rearrangement [17,18]. The continuous investigation on G. hanburyi in our laboratory led to a series of reports of gambogic acid derivatives with anticancer activities [5,10,[19][20][21][22][23][24].…”