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New Route to Chiral Heteromacrocycles

P.A. Petukhov*, A.V. Tkachev, Yu.V. Gatilov, T.V.Rybalova

Novosibirsk Institute of Organic Chemistry, Lavrentjev Ave. 9, Novosibirsk 630090, Russia

Macrocycles widely used as catalysts phase-transfer catalysis, different kind sensors, enzymes models, etc.1 We report here the new short route to new optically active heteromacrocycles from natural terpenes. The first step is the transformation of olefins 1 to diaminodioximes 5 (Scheme 1). The diaminodioximes derived from simple olefins are known as ligands for the preparation of the compounds used in radiomedicine.2 We synthesized five new diaminodioximes 5a - 5e from (+)÷3÷carene and a-pinene as olefins and ethylenediamine, hexamethylenediamine and piperazine as diamines. The main by-products were diaminooximes 4. Unfortunately our attempts to involve diaminooximes 4 in the reaction with corresponding nitrosochloride 2 were failed.

Scheme 1.


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The next step is intramolecular binding of oximes group of diaminodioximes by methylene fragment under phase transfer conditions (Scheme 2). The reaction of this type was previously used for preparation achiral macrocycles from dioximes.3

Scheme 2.

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Molecular modelling using MM2 and PM34 has shown that diaminodioximes 5a - 5e has linear structure (Figure 1). Moreover hydroxyl groups of diaminodioximes 5a - 5e could be intramolecularly linked without additional deformation of terpenic carbocycles only in the case of compounds 5b, 5d and 5e.

Figure 1. The structure of diaminodioxime 5a (MM2 calculations).

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Nevertheless four new optically active macrocycles 6a, 6b, 6d, 6e were synthesized (Scheme 2) under phase transfer conditions from diaminodioximes and methylene chloride. All macrocycles are colorless crystal compounds with low solubility in water and good solubility in low polar organic solvents (octane, benzene). The structure of the macrocycles were confirmed by various spectral methods (IR, NMR 1H and 13C, HRMS) and elemental analysis. The x-ray crystal analysis of macrocycle 6a showed a structure with C2 symmetry and deformed conformation of terpenic carbocycles comparing to diaminodioxime 5a (Figure 2). The NMR data have shown that the conformation of terpenic carbocycles in 6b, 6d and 6e is nearly the same as in the diaminodioximes 5b, 5d and 5e.

Figure 2. The x-ray structure of 6a.

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1. Dietrich B., Viout P., Lehn J.-M., Macrocyclic chemistry: aspects of organic and inorganic supramolecular chemistry, Wieheim; New York; Basel; Cambrindge: VCH, 1992.
2. U.S. Patent. 5663307, 1997.
3. Hosokawa T., Ohta T., Murahashi S. Synthesis of Novel Heteromacrocyclic Compounds from (E,E)-1,2-Diketone Dioximes and Dichlormethane. J. Chem. Soc. Chem. Commun., 1982, 7-9.
4. CS Chem3D Pro 4.0 included in CS ChemOfficePro 4.5 Software.