Synthetic Approaches to the Anticancer Agent Fredericamycin A

Abstract

In this minireview, we have highlighted various developments related to the total synthesis of an anticancer agent, fredericamycin A (NSC-305263). The presence of a unique molecular architecture and significant biological properties associated with fredericamycin A have greatly enhanced the research activity, and we cover the total synthesis of this molecule since its isolation. Different methodologies adopted for the construction of the stereo-genic spiro centre are radical spirocyclization, Diels À Alder (DA) reaction, [3 + 2] annulation, photochemical approach, ring-closing metathesis (RCM), palladium-catalyzed crosscoupling reaction, rearrangement approach, benzannulation etc. This minireview provides an overview of the contribution of different research groups in the total synthesis of fredericamycin A. We also cover various model studies related to the synthesis of this molecule.

Chiral Isochalcogenourea‐Catalysed Enantioselective (4+2) Cycloadditions of Allenoates

“…In addition, potential products like the spirocyclic compounds 5 or the (dihydro)pyrane‐containing 3 and 4 represent interesting targets because of the well‐described biological properties associated to these important scaffolds (which are also frequently found in natural products). [ 18 , 19 ] In this manuscript we demonstrate for the first time that allenoate‐activation using IT(Se)U catalysis is indeed possible and allows for formal (4+2) cycloadditions yielding dihydropyrane derivatives ( Z )‐ 3 in a highly enantioselective fashion by using these easily accessible bench stable chiral Lewis base organocatalysts. In addition, the factors governing enantioselectivity and the origin of the observed differences in reactivity between tertiary phosphine‐, DABCO‐ and IChU‐catalysed reactions are also explained.…”

“…Thus, we were hoping that the unprecedented use of IChU will allow for alternative cycloaddition pathways, even in a stereocontrolled manner. In addition, potential products like the spirocyclic compounds 5 or the (dihydro)pyrane‐containing 3 and 4 represent interesting targets because of the well‐described biological properties associated to these important scaffolds (which are also frequently found in natural products) [18,19] . In this manuscript we demonstrate for the first time that allenoate‐activation using IT(Se)U catalysis is indeed possible and allows for formal (4+2) cycloadditions yielding dihydropyrane derivatives ( Z )‐ 3 in a highly enantioselective fashion by using these easily accessible bench stable chiral Lewis base organocatalysts.…”

Chiral Isochalcogenourea‐Catalysed Enantioselective (4+2) Cycloadditions of Allenoates

“…In addition, potential products like the spirocyclic compounds 5 or the (dihydro)pyrane‐containing 3 and 4 represent interesting targets because of the well‐described biological properties associated to these important scaffolds (which are also frequently found in natural products). [ 18 , 19 ] In this manuscript we demonstrate for the first time that allenoate‐activation using IT(Se)U catalysis is indeed possible and allows for formal (4+2) cycloadditions yielding dihydropyrane derivatives ( Z )‐ 3 in a highly enantioselective fashion by using these easily accessible bench stable chiral Lewis base organocatalysts. In addition, the factors governing enantioselectivity and the origin of the observed differences in reactivity between tertiary phosphine‐, DABCO‐ and IChU‐catalysed reactions are also explained.…”

Annulations involving 1-indanones to access fused- and spiro frameworks

“…10 Fredericamycin A obtained from Streptomyces griseus displays antitumor/anticancer activity. 11,12 Euplectin (and coneuplectin), derived from the Lichen Flavoparmelia euplecta was found to exhibit promising cytotoxic and other biological activities. 13 Likewise, several spirobenzylisoquinoline alkaloids containing indanone motif, viz.…”