The Total Synthesis of Inostamycin A

Abstract

The first total synthesis of inostamycin A is described. With efficient and stereoselective synthetic routes to aldehyde 3 and ketone 4 developed through asymmetric aldol reactions, addition reactions and reduction, and with chiral building blocks, the two large fragments were coupled with remarkable anti stereoselectivity and efficiency by aldol condensation. The coupling reaction provided the complete carbon skeleton with all the requisite functional groups and stereogenic centers for inostamycin A. The two quaternary carbons at C20 and C16 of ketone 4 were elaborated in a highly stereocontrolled manner by addition reactions of the transmetallated 5 to ethyl ketone 6 and the transmetallated 7 to methyl ketone 8, respectively, in which the use of LaCl3 for transmetallation was critical for high coupling efficiency.

Modelos estereoquímicos de adição à carbonila

“…MH816-AF15, e que apresenta atividade antimicrobiana e citotóxica. 24 Devido ao seu mecanismo de ação, apresenta também a capacidade de regeneração da citotoxicidade do paclitaxel e supressão citostática de recorrência de tumores. Durante a rota sintética, a formação do álcool terciário 19 foi obtida mediante adição do reagente organolítio 17 à cetona 18, na presença de LaCl 3 , que levou exclusivamente à formação do produto de Felkin 19 como único diastereoisômero (Esquema 12).…”

Tunable Reaction Mode of Bifunctional Peroxides with Ketones to Access α-Oxacyclic Ketones and Enals

“…Ketones bearing α-oxacycle motifs are present in many biologically active natural products and serve as advanced intermediates toward complex structures . Basically, they were prepared in multiple steps, but the straightforward and highly efficient one-step strategies remain limited. − Early methods involved the acid-promoted or Lewis-acid-catalyzed − addition of β-keto esters to cyclic enol ethers to provide this type of product.…”