Synthesis of (±)‐Setigerumine I: Biosynthetic Origins of the Elusive Racemic Papaveraceae Isoxazolidine Alkaloids**

Abstract

The biosynthetic origins of the structurally related racemic isoxazolidine Papaveraceae alkaloids Setigerumine I, Dactylicapnosinine and Dactylicapnosine have remained elusive since their original isolation over two decades ago. Herein we report the first biosynthetic hypothesis for their formation and, inspired by it, the first synthesis of (±)‐Setigerumine I with accompanying computational rationale. Based on the results, these isoxazolidine alkaloids arise from racemizing oxidative rearrangements of prominent isoquinoline alkaloids Noscapine and Hydrastine. The key steps featured in this synthesis are a room temperature Cope elimination and a domino oxidation/inverse‐electron demand 1,3‐dipolar cycloaddition of an axially chiral, yet configurationally unstable, intermediate. The work opens this previously inaccessible family of natural products for biological studies.

In Silico Design, Synthesis, and Evaluation of Novel Enantiopure Isoxazolidines as Promising Dual Inhibitors of α-Amylase and α-Glucosidase

“…Additionally, some natural isoxazolidine derivatives are known for their diverse biological activities [ 21 , 22 , 23 ] ( Figure 1 ), such as anticancer [ 24 ], antibacterial [ 25 ], antifungal [ 26 ], and antioxidant [ 27 ] properties. Isoxazolidine analogs have also been used as a key intermediate to obtain natural compounds of high biological importance [ 28 , 29 , 30 ], such as 4-hydroxyisoleucine [ 31 ], a natural hypoglycemic agent.…”

Harnessing NHC/Base-Catalyzed Regiodivergent Oxidative Cyclization for Versatile Aminolactone Synthesis

“…Lactones such as phthalides and isocoumarins are important O -heterocycles that exhibit various biological properties and are utilized as versatile building blocks in organic synthesis . Among them, amino-substituted phthalides and isocoumarins are prevalent structural motifs found in natural products and pharmaceuticals . Therefore, the selective synthesis of these two different lactones from the same substrate by tuning reaction parameters is highly efficient and desirable.…”

Biomimetic Dehydroamination of Primary Amines

“…While Cope elimination involves the oxidation of t -amines with peroxides. The production of the alkenes mostly requires harsh thermal and vacuum conditions (Scheme b) . In addition, unlike alcohols, Burgess reagent proved to be an unsuccessful defunctionalization reagent …”