A-ring and E-ring modifications of the cytotoxic alkaloid Luotonin A: Synthesis, computational and biological studies

Cyclizations of Alkenyl(Alkynyl)‐Functionalized Quinazolinones and their Heteroanalogues: A Powerful Strategy for the Construction of Polyheterocyclic Structures

“…In this context, much attention is focused on new synthetic approaches to the five-cyclic core of this alkaloid as well as on its functionalization. [143][144][145][146][147] One of the effective strategies to prepare various A-and E-ring substituted luotonin A derivatives 129 involves, as a key stage, the intramolecular [4 + 2]-cycloaddition of intermediate A formed upon treatment of 3-propargyl-4-oxo-3,4-dihydroquinazoline-2-carboxanilides 128 with in situ prepared Hendrickson reagent [(Ph 3 P + ) 2 O(TfO À ) 2 ] (Scheme 46). [138][139][140][141][142][143] This version of the aza-Diels-Alder reaction allows the simultaneous formation of the B and C rings of luotonin.…”

“…Important representatives of quinazolinone alkaloids are luotonin A ( 6 , see Figure 1) and its derivatives, which show significant cytotoxic activity against murine leukemia P388 cells and a number of human large‐cell lung carcinoma H460 cells. In this context, much attention is focused on new synthetic approaches to the five‐cyclic core of this alkaloid as well as on its functionalization [143–147] . One of the effective strategies to prepare various A‐ and E‐ring substituted luotonin A derivatives 129 involves, as a key stage, the intramolecular [4+2]‐cycloaddition of intermediate A formed upon treatment of 3‐propargyl‐4‐oxo‐3,4‐dihydroquinazoline‐2‐carboxanilides 128 with in situ prepared Hendrickson reagent [(Ph 3 P + ) 2 O(TfO − ) 2 ] (Scheme 46).…”

“…One of the effective strategies to prepare various A‐ and E‐ring substituted luotonin A derivatives 129 involves, as a key stage, the intramolecular [4+2]‐cycloaddition of intermediate A formed upon treatment of 3‐propargyl‐4‐oxo‐3,4‐dihydroquinazoline‐2‐carboxanilides 128 with in situ prepared Hendrickson reagent [(Ph 3 P + ) 2 O(TfO − ) 2 ] (Scheme 46). [138–143] This version of the aza‐Diels‐Alder reaction allows the simultaneous formation of the B and C rings of luotonin.…”