Synthesis of a novel polycyclic ring scaffold with antimitotic properties via a selective domino Heck–Suzuki reaction

Abstract

The synthesis of a previously undescribed sp3-rich 6-5-5-6 tetracyclic ring scaffold using a palladium catalysed domino Heck–Suzuki reaction is reported.

Recent Advances in Transition Metal‐Catalyzed Domino‐Cyclization Strategies for Functionalized Heterocyclic/Carbocyclic Compounds

“…In 2015, Esther Alza [106] et al. have demonstrated the synthesis of Sp 3 ‐rich 6‐5‐5‐6 tetracyclic ring scaffolds 325 from functionalized bicyclo [3.2.1] octadienes 318 on reaction with boronic acid 319 through Pd‐catalyzed domino Heck‐Suzuki reaction sequence (Scheme 66).…”

A novel route for the synthesis of alkanes from glycerol in a two step process using a Pd/SBA-15 catalyst

“…The reaction was investigated with different solvents such as 1,4-dioxane, DMF and DMSO; moreover, the choice of solvents had a signicant impact on C-C bond formation. 36,37 Among the solvents examined, 1,4-dioxane was the most efficient with complete conversion of 1,2,3-tribromopropane for the formation of the alkyl-alkyl Suzuki coupling reaction, and DMSO and DMF exhibit 39% and 79% conversion of 1,2,3-tribromopropane and also afforded the desired product in a slightly less selectivity (Fig. 7c).…”

Bioactive Compound Collections: From Design to Target Identification

“…In addition to gold, other metals have the ability to catalyze diverse processes to obtain various scaffolds from the same starting material, including palladium. 48 An interesting example of its use to steer reactivity in two opposing directions to yield different products was reported by Alza et al 51 Starting from the oxidative insertion of palladium into multifunctional intermediate 56, two possible reaction pathways were observed. Transmetalation with boronic acids led to the direct Suzuki product 59, 52 whereas a syn-migratory insertion followed by transmetalation led to a 6-5-5-6 fused-ring system (62) by a domino Heck-Suzuki-type process (Figure 12).…”

“…The anti-mitotic activity of dosabulin and HS-1 was identified by this approach (Figure 12). 51,52 Another phenotype that can be successfully studied by image-based screening is autophagy. Autophagy is a conserved cellular mechanism for the degradation and recycling of cellular waste material as well as pathogens and is upregulated in situations of stress, such as nutrient deprivation (Figure 13A).…”