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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

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Record number 321062
Title Potato glycoalkaloids as starting material for the synthesis of steroid hormones
Author(s) Vronen, P.J.E.
Source Wageningen University. Promotor(en): Aede de Groot, co-promotor(en): J.B.P.A. Wijnberg. - [S.I.] : S.n. - ISBN 9058088340 - 114
Department(s) Laboratory for Organic Chemistry
EPS-3
Publication type Dissertation, internally prepared
Publication year 2003
Keyword(s) glycoalkaloïden - steroïdhormonen - synthese - solanidine - glycoalkaloids - steroid hormones - synthesis
Categories Organic Chemistry
Abstract

Since the first structure elucidation of solanidine about 70 years ago, there has been an interest to convert this aglycon to an intermediate suitable for the synthesis of steroids. A renewed interest in this conversion is stimulated by the rising prices of the present starting material diosgenine . Diosgenine is found in Costus speciosus grown in China and the availability and monopoly position of China for diosgenine is of growing concern.

In the potato starch production the glycoalkaloidsa-chaconine anda-solanine are first concentrated in the protein fraction. The latter can be upgraded by removal of the glycoalkaloids which ends up in a waste fraction. A procedure is available to isolate these glycoalkaloids from this waste and in principle they can be made available as alternative for diosgenine as starting material for the production of dehydropregnenolon acetate (DPA).

To obtain the starting material for our research, an improved simple and effective method has been developed for the isolation of the potato glycoalkaloids,a-chaconine anda-solanine, from the residual protein waste fraction which was obtained from AVEBE. The hydrolysis of these glycoalkaloids to solanidine has been accomplished by mild acid treatment

The conversion of solanidine to DPA was first tried by a recently published method using Hg(OAc) 2 as oxidation reagent. Although the first steps could be improved by combining the Hg(OAc) 2 oxidation with the isomerization step in a one pot synthesis, the crucial oxidation of the intermediate enamine could not be accomplished

In the second attempt to convert solanidine to DPA the Cope and Polonovski reactions were studied and to do so it was necessary to synthesize solanidine N -oxide first. It turned out that the Cope reaction can not give the desired results because a 5-membered planar transition state necessary for the Cope reaction is not possible in these systems. The Polonovski reaction can be carried out with Ac 2 O or (CF 3 CO) 2 O under rather extreme conditions. With Ac 2 O no reaction was observed for solanidine N -oxide or 3-acetoxysolanidine N -oxide. Treatment of 3-acetoxysolanidine N -oxide with (CF 3 CO) 2 O yielded a new trifluoroacylated compound but no further attempts were undertaken to convert the new trifluoroacylated compound into DPA .

The third option was to open the E,F-ring system using the Von Braun reaction. Besides the desired major E-ring opened compound also the minor F-ring opened compound was isolated. Alternatives for the hazardous Von Braun reagent BrCN were investigated but without success. Calculations confirmed the unique properties of BrCN and led to the conclusion that this is one of the few reagents capable of opening ring E of solanidine. The next step was the conversion of the E-ring opened compound to DPA via the Hofmann degradation. Only Hofmann degradation of the ammonium salt containing theD16,17double bond with LDA yielded the triene and the monomethylated diene which in principle can be remethylated and subjected again to Hofmann Although Hofmann degradation gives the desired triene further degradation to DPA requires several protection and deprotection steps which are not very attractive for industrial application.

As a last option, the known conversion of 3-acetoxysolanidine to spirosolane compounds followed by conversion to DPA has been investigated. DPA could be obtained starting from 3-acetoxysolanidine in 9 reaction steps in 30% overall yield. Extensive research was performed on finding shortcuts in this route but despite all our efforts, further shortening of the route from 3-acetoxysolanidine via tomatidenol to DPA could not be accomplished.

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