Attempted [2]Catenane Synthesis via a Quasi[1]catenane by a Templated Backfolding Strategy

A templated backfolding concept to construct a [2]catenane was attempted via a quasi[1]catenane showing an inverted spiro geometry. The template is covalently connected to the ketal-connected semi-perpendicular-arranged linear precursors and spatially directs the sterically congested backfolding macrocyclizations that are required to give a quasi[1]catenane. So far, we are unable to hydrolyze the cyclic ketal to liberate the [2]catenane

Consecutive Pictet-Spengler Condensations toward Bioactive 8-Benzylprotoberberines: Highly Selective Total Syntheses of (+)-Javaberine A, (+)-Javaberine B, and (-)-Latifolian A

Enantiopure 8-benzylprotoberberines were synthesized by two consecutive Pictet-Spengler (PS) condensations with protected 3,4-dihydroxyphenylacetaldehydes. The first PS to (+)-(R)-norprotosinomenine was optimized to 90 % ee with 5 mol-% of (R)-TRIP as chiral Bronsted acid (> 99 % ee after trituration). The second PS did not require any catalyst, and its regioselectivity was strongly dependent on the solvent: 99: 1 para selectivity was obtained in trifluoroethanol leading to (+)javaberine A; 81: 19 ortho selectivity was reached in apolar aprotic solvents for the synthesis of (+)-javaberine B. Complete, natural diastereoselectivity was observed in the second PS. Through selective catechol oxidation the spirocyclic alkaloid (-)-latifolian A was prepared from protected (+)-javaberine A

Synthesis of spiro quasi[1]catenanes and quasi[1]rotaxanes via a templated backfolding strategy

Due to their well-defined three-dimensional geometry, spiro compounds are widely utilized in drug research. From the central tetrahedral carbon atom, besides the regular structure, an inverted spiro connectivity may be envisioned. Here we disclose the synthesis of this molecule class that we have coined quasi[1]catenanes. Next to their fascinating and aesthetic shape, the higher compactness as compared to regular spiro bicycles is noteworthy. To enable synthetic access to compact entangled multimacrocyclic molecules, we have developed a new strategy. The key element is a template, which is covalently connected to the linear precursors, and spatially directs the sterically congested backfolding macrocyclizations that are required to give quasi[1]catenanes. Similarly, quasi[1]rotaxanes are made