O.T. Zhilkibayev

The Kazakh national university after al-Farabi, Almaty, Kazakhstan

Zhilkibaevoral@mail.ru

diastereoselective synthesis of 1-[2-(3΄, 4΄- dimethoxy-phenyl)ethyl]-2-phenyldecahydroquinoline-4-ONE

Last years, the chemistry of decahydroquinoline alkaloids has received a new impulse in the development. The literary data on biological activity of decahydroquinoline alkaloids, and also the experience stored by this time on their synthesis opens prospects for creation of new more effective medical preparations products with directional effect and agrochemicals.

decahydroquinoline backbone is a structural basis of many natural alkaloids (lepadines, pumiliotoxins at al.) in possession of different biological activity. Introduction in to decahydroquinoline skeleton the pharmacogenetic fragments often meeting in structure of natural alkaloids and working out of the directed synthesis of new highly effective biologically active compounds is an actual problem of modern organic and bioorganic chemistry.

Such approach used at preparation of 1-[2-(3΄, 4΄- dimethoxyphenyl) ethyl]-2-phenyldecahydroquinoline-4-one (4). At a choice of amine a natural alkaloid, close by structure, – messine - 2 (3 ', 4 ', 5 '-trimethoxyphenyl) ethylamine has been accepted as a basis. The combination in one molecule of decahydroquinoline skeleton and dimethoxyphenylethyl group in the synthesised compounds do them close structural analogues of such natural alkaloids and spasmolytic aslobinaline, salsolidine, papaverine, no-spa, etc. [1-8]. Earlier the synthesis of this decahydroquinolone (4) is carried out by heterocyclization of styryl-1-cycklohexenylketon with homoveratrylamine (2) in absolute ethanol. As a result of reaction a mix of a trans- and cis-aminoketones is produced, yield 67 %, with considerable prevalence of a trans-isomer in which the phenyl group at С² is focused equatorially. The content of a cis-isomer about 2 % [9,10].

For the purpose of yield increase it is carried out one-stage diastereoselective synthesis of this aminoketone (4) by stirring of equimolar mix of benzaldehyde, homoveratrylamine and acetylhexene at room temperature in presence of trace of iodine. As a result the trans-isomer of 1-[2-(3΄, 4΄- dimethoxyphenyl) ethyl]-2-phenyldecahydroquinoline-4-one (4) with yield 91 % is obtained.

The structure of aminoketone 4 is determined with the help of IR- , a nuclear magnetic resonance (NMR) ¹Н spectroscopy.

In IR-spectra of stereoisomer 4, there are intensive absorption bands in the region of 1700-1715 sm^-1, characteristic to valence fluctuations of carbonyl group.

In NMR ¹Н spectra of stereoisomer 4 it is found out a weak field signal in area d 3,86 ppm, (except for signals of protons of aromatic rings), which is caused by proton Н² and observed in the form of a doublet (²J 12,5 Hz) and doublets (²J 2,4 Hz). Vicinal constants testify to an equatorial arrangement of phenyl at С². Though signals of angular protons also get to resonance area methylene protons of substitute at nitrogen, the signal structure at С9 however is distinctly shown, on which it is possible to judge a way of a joint of cycles. This signal represents a triplet (²J 10,0 Hz), doublets (²J 3,2 Hz) that is characteristic for a trans-joint of cycles.

Table 1. NMR ¹Н spectra of decahydroquinolone-4

Index of compound	d, ppm in CDCl3					КССВ, J, Hz
	Н^2	Н^3а	Н^3е	Н^9	Н^10	Н^2Н^3а	Н^2Н^3а	Н^3аН^3е
4	3,86	2,74	2,45	2,51	2,32	12,5	2,4	13,8

On the basis of the above-mentioned data to aminoketone 4 the following configuration is attributed:

If heterocyclization of styryl-1-cycklohexenylketon with homoveratrylamine, earlier carried out by us, led to formation of a mix of trans- and cis-aminoketones, with considerable prevalence of trans-isomer, one-stage three-component synthesis goes stereo-directly with formation only one stereoisomer with a trans-joint of cycles and equatorial orientation of phenyl group at С².

references

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