Evolution of Natural Product Scaffolds by Acyl- and Arylnitroso Hetero-Diels−Alder Reactions: New Chemistry on Piperine

Abstract

Piperine, a natural product containing a conjugated diene, was reacted with polymer-supported acyl- and arylnitroso dienophiles. The reactions with arylnitroso dienophiles were also carried out in solution. The oxazine rings formed by the corresponding hetero-Diels-Alder reactions were further transformed and novel acyclic as well as heterocyclic derivatives including pyrroles and quinoxalinones were prepared.

Preparation and biological evaluation of novel leucomycin analogs derived from nitroso Diels–Alder reactions

“…4 a Clearly, 6-methyl-2-nitrosopyridine 4a , as a stabilized form of iminonitroso reagent, constitutes an ideal combination of reactivity and stability for NDA reactions with leucomycin A7, relative to benzenenitroso 2 and acylnitroso agent 3 , respectively.…”

“…Our effort in this area has involved nitroso Diels–Alder (NDA) reactions as efficient methods for derivatization and functionalization of diene-containing natural products. 4 Our early research has demonstrated that several complex diene-containing natural products, including leucomycin A7 5 (also known as turimycin H3) (Fig. 1), readily undergo nitroso cycloadditions, generating 1-amino-4-hydroxy-2-ene heterocycle scaffolds with high regio- and stereoselectivity.…”

“…1), readily undergo nitroso cycloadditions, generating 1-amino-4-hydroxy-2-ene heterocycle scaffolds with high regio- and stereoselectivity. 4 a Our continued interest in natural product derivatization encouraged us to further explore the scope and limitation of this chemistry. In this regard, leucomycin A7, as a representative natural macrolide antibiotic containing a conjugated diene was chosen for further investigation of this method for m odular e nhancement of N ature's d iversity (MEND).…”

Hetero‐Diels‐Alder‐Reaktionen von Nitrosocarbonylverbindungen als nützliches Verfahren in der organischen Synthese

“…[182] Piperin (177), eine der Hauptkomponenten von Pfeffer, reagierte mit polymergebundenen Nitrosocarbonylspezies nach Entschützen zu den Cycloaddukten 178 und 179 (Schema 32). [183] Die Autoren waren überrascht darüber, dass bei der Behandlung mit TFA und Triethylsilan zum Abfangen von Kationen aus 178 das Hydroxylamin 180 entstand. Unter den gleichen Bedingungen wurde das Cycloaddukt 179 unverändert aus dem Reaktionsgemisch zurückgewonnen.…”

Highlights in the solid-phase organic synthesis of natural products and analogues

“…Krchnak and co-workers 27 described the synthesis of new pyrrole and quinoxalinone analogues. The strategy involved the cycloaddition of piperine, a natural conjugated diene, with polymer supported acyl-and arylnitroso dienophiles 136 (Scheme 19).…”