Biomimetic Synthesis of Dimeric Metabolite Acremine G via a Highly Regioselective and Stereoselective Diels−Alder Reaction

Abstract

The dimeric metabolite acremine G was synthesized featuring a highly regioselective and stereoselective Diels-Alder reaction between a TBS-protected hydroquinone diene and a structurally related alkenyl quinone. The major endo [4 + 2] adduct slowly transforms to acremine G by the atmospheric air under the deprotection conditions (in situ generated HF).

Recent advances in 1,4-benzoquinone chemistry

“…Stratakis and co-workers 322 reported an efficient biomimetic route to acremin G (219) featuring a highly regioselective and stereoselective Diels-Alder reaction between a TBS-protected hydroquinone diene (216) and a structurally related alkenyl quinone (217). The endo [4+2] cycloadduct (218) slowly transforms to acremin G (219) by the atmospheric air under deprotection conditions (Scheme 64).…”

A Strategy toward the Biomimetic Synthesis of (±)-Morusalbanol A Pentamethyl Ether

“…Finally, the allylic alcohol 17 was dehydrated to give diene 11 on treatment with acetyl chloride/pyridine. 9 The synthesis of dienophile 12 commenced with methyl ether protection of the para-hydroxy group in compound 18 to give acetophenone 19 (Scheme 4). Subsequent Claisen-Schmidt condensation with 2,4-dimethoxybenzaldehyde gave dienophile 12 in 72% overall yield (two steps).…”

Six‐Membered Carbocycles

“…Rawal combined a cyclohexadienone with a Danishefsky-type diene to yield a c/s-decalin in his total synthesis of platencin. 100 Stratakis also generated a cis-decalin upon combination of a quinone dienophile and an acyclic diene during the production of acremine G. 101 Nakamura and Hashimoto employed an intermolecular Diels-Alder reaction for the construction of the G ring in pinnatoxin A. 102 Danishefsky reacted a vinylindene diene with a quinoneketal dienophile to form the tetracyclic framework of fluostatin C. 103 In Nicolaou's synthesis of the bisanthraquinone antibiotic BE-43472B, he initiated a fascinating late-stage cascade by the reaction of a functionalized acyclic diene with a pentacyclic quinone dienophile.…”