Heteroring‐Annulated Pyrrolino‐Tetrahydroberberine Analogues

Abstract

Af acile method for the synthesis of pyrrolino-tetrahydroberberine derivatives startingf rom 1,2-diaza-1,3dienes and dihydroberberines is reported. The synthesis is ac ascade reactioni nvolving aM ichael-typea ddition of the enaminem oiety of dihydroberberine to an azo-enes ystem, followed by nitrogen cyclization on the resulting iminium ion.[a] G.Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under http://dx.Figure 2. Pyrrolo[2,3-b]pyridine core of chaetominines and kapakahines and of isoschizogaminea nd isoschizogaline. Scheme1.Retrosynthetic analysis of pyrrolo[2,3-b]pyridine systems.Scheme2.Synthesis of 7,8-dihydroberberine 2 [14] and of 8-acetonyl-7,8-dihydroberberine 3, [15] starting from commercial berberinechloride 1.Scheme3.Proposed mechanism for the synthesis of fused pyrrolino-THBderivative 6e.2 96 3 72[a] Isolated yields of fused pyrrolino-tetrahydroberberine derivatives 6.[ b] All of the reactionstook placewithin 0.25 h.

Recent Advances in the Chemistry of Conjugated Nitrosoalkenes and Azoalkenes

“…In this context, a decisive contribution to synthesis of the isoquinolyl family alkaloid tetrahydroberberine has been reported. This included Michael addition of the enamino functionality of 7,8-dihydroberberine derivatives to azoalkenes, as well as the preparation of deaza analogues of the bisindole marine alkaloid Topsentin 335 , obtained by the addition of 1,3-di­(3-indolyl)­propan-1,3-diones 333 to azoalkene 334 (Scheme ). A similar strategy involving a double Michael addition followed by azacyclization of 1,2-diaza-1,3-butadienes with 2-oxoindoles, barbiturates, and rhodanine gave 2-oxospiro­[indole-3,4′-pyridines], spirobarbiturate pyridines, and 2,3,5,6-tetrahydro-1 H -pyrrolo­[3,4- c ]­pyridine-1,3,6-triones, respectively.…”

Synthesis of new dihydroberberine and tetrahydroberberine analogues and evaluation of their antiproliferative activity on NCI-H1975 cells

“…On the other hand, we have recently demonstrated that some structurally complex THBER analogues, namely pyrrolino-tetrahydroberberines, synthesized by some of us [ 68 ], exhibited enhanced antioxidant properties in comparison to THBER against a wide variety of pathophysiologically relevant oxidants such as peroxyl radicals, ferrous ion, and hydrogen peroxide [ 65 ].…”

Diaza-1,3-butadienes as Useful Intermediate in Heterocycles Synthesis

“…The enamine moiety of 7,8-dihydroberberine 6 attacks a 1,2-diaza-1,3-diene 7 intermediate, resulting in non-isolable zwitterionic hydrazones 8 . The formation of the 2-pyrroline ring of the 5 is favored by intramolecular nitrogen nucleophilic attack on the iminium function due to the loss of hydrogen at the α-position of the hydrazine moiety of 8 ( Scheme 2 ) [ 28 , 29 ]. The reaction proceeds under mild conditions to afford the product good to excellent yields after only 15 min of reaction.…”