73(P-61) Asymmetrical Synthesis of (-)-Dihydrocuscohygrine Using Diastereoselective Addition of Bisoxazolidine with Grignard Reagent
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Dihydrocuscohygrine, C_2-asymmetrical pyrroridine alkaloid, was isolated from Erythroxylon Coca leaves by Turner in 1981. We show here synthetic studies on dihydrocuscohygrine using 6 as a starting material. Our labolatory have been developed that C_2-asymmetrical bisxazolidine obtained easily from 6 and dialdehyde was reacted with Grignard reagent to afford diamine with high diastereoselectivity. First, we tried the synthesis of (-)-deoxycuscohygrine which bisxazolidine(7) could be prepared more simply. A key reaction, addition reaction to bisxazolidine with 1,3-dioxanylethylmagnesium bromide as Grignard reagent proceeded to afford 13 preferentially. Acidic cyclization of 13 provided the desired product(14), which was transformed to 1 via hydrolysis with Raney Ni in methanol. Asymmetrical synthesis of (-)-deoxycuscohygrine was accomplished from bisoxazolidine(7) in 4 steps. Similarly, asymmetrical synthesis of (-)-dihydrocuscohygrine carried out using addition reaction of Grignard reagent to bisoxazolidine(19) prepared from 15 gave diamine(20) with high diastereoselectivity. The absolute configuration at stereogenic center was established as R,R by X-ray analysis of a single crystal of 21. C_2-Asymmetrical synthesis of (-)-dihydrocuscohygrine was also accomplished from 15 in 10 steps and 9% overall yield.
