One‐Step Multigram‐Scale Biomimetic Synthesis of Psiguadial B

Abstract

A gram-scale synthesis of psiguadial B, a purported inhibitor of human hepatoma cell growth, has been achieved in one step by a biomimetic three-component coupling of caryophyllene, benzaldehyde, and diformylphloroglucinol. This cascade reaction is catalyzed by N,N'-dimethylethylenediamine, and proceeds at ambient temperature to generate four stereocenters, two rings, one C-O bond, and three C-C bonds. Combined computational and experimental investigations suggest the biosynthesis of the natural product is non-enzyme mediated, and is the result of a Michael addition between caryophyllene and a reactive ortho-quinone methide, followed by two sequential intramolecular cationic cyclization events.

Six domoic acid related compounds from the red alga, Chondria armata, and domoic acid biosynthesis by the diatom, Pseudo-nitzschia multiseries

“…Another Michael-type cyclization precursor similar to 12 was also proposed by Wright’s group 22 . Michael-type cyclization reactions have been reported in many biosynthetic routes, for example, psiguadinal B 31 . Interestingly, as a possible cyclization precursor of acromelic acid, another kainoid from the poisonous mushroom, Clitocybe acromelalga , a structurally related compound to 4 ( l - N -[2-(3-Pyridyl)ethyl]-glutamic acid) has been reported 32 .…”

Isolation and Synthesis of Novel Meroterpenoids from Rhodomyrtus tomentosa: Investigation of a Reactive Enetrione Intermediate

“…With 13 a and 13 b in hand, we initiated studies towards syntheses of 5 – 11 . Initial reactions of either endoperoxide 13 a or 13 b and trans ‐caryophyllene in polar solvents such as dichloromethane, dichloroethane, nitromethane, trifluoroethanol, and HFIP were unfruitful. Following reaction conditions reported by Takao and co‐workers, thermolysis of 13 a in the presence of caryophyllene in toluene at 100 °C afforded 9 , 10 , and 11 , in 10, 10, and 6 % yields, respectively.…”

“…The assigned configurations of the dihydropyrans 8 – 11 indicate both conformers may react with 14 by a hetero‐Diels Alder (HDA) cycloaddition (Scheme e) ,–. In contrast stepwise Michael addition of the βα conformer of caryophyllene ( re ‐face approach Scheme c) to 14 may also afford the zwitterion 15 , which, after bond‐rotation to 16 , may undergo consecutive cyclization to 5 . Bis ‐furan 6 may also be obtained through a similar stepwise Michael addition of the ββ conformer ( si ‐face approach, Scheme d) to 14 may afford 17 , which can undergo cyclization to 6 .…”

Synthesis of 6,12-Disubstituted Methanodibenzo[b,f][1,5]dioxocins: Pyrrolidine Catalyzed Self-Condensation of 2′-Hydroxyacetophenones

“…Heterocyclic compounds possess fascinating complex structural architecture and are key structural motifs in an array of biologically active natural products and pharmaceutically active compounds [1], which drives the development of improved and new synthetic methodologies [2,3,4,5,6,7,8,9]. In recent years, cascade reactions [10,11,12,13,14,15,16] and bio-inspired technologies [17,18,19,20,21,22,23] have been employed to access structural complexity in compounds of biological importance.…”