ИСТИНА

In contrast to classical combinatorial chemistry, which aim to access precise or dense region of chemical space, diversity-oriented synthesis (DOS) populates chemical space broadly with molecules having diverse molecular scaffolds. The goals of DOS include the development of pathways leading to the efficient synthesis of collections of small molecules having skeletal and stereochemical diversity with defined coordinates in chemical space [1]. Tandem polyepoxide cyclisations [2] is an extraordinary reaction in the context of DOS. The remarkable functional group tolerance combined with ability to form rings of varied sized gives this class of reactions workable generality. Applying this approach, synthesis of set cyclic polyethers scaffolds was performed using isonipecotic acid, geraniol, nerol and farnesol as commercially available starting materials. The terpenoid fragment was introduced via alkylation reaction. After reduction with Red-Al chiral epoxidation was performed in presence of Shi ketone [3]. Subsequent tandem polyepoxide cyclisations at various conditions led to formations of different type polycyclic scaffolds. Scope and limitations of the reactions are discussed. 1 Burcke, M.D.; Schreiber, S.L. Angew.Chem.Int.Ed. 2004, 43, 46-58 2 McDonald, F.E.; Tong, R.; Valentine, C.J.; Bravo, F.; Pure.Appl.Chem.2007, 79, 281-291 3 Wong, O.A.; Shi, Y.; Chem.Rev.2008, 108, 3958-3987