Mitchell, William

2019-02-15T14:37:27Z

2019-02-15T14:37:27Z

1939

1. The alkaloidal content of the Australian drug, Duboisia myoporoides, has been examined. Despite the claims of most of the earlier workers, no trace of hyoscyamine has been isolable from any of a large number of samples. In addition to hyoscine, four new alkaloids have been found: tigloidine (0.1%), valeroidine (0.1%), poroidine, and isoporoidine, the last two being isolated as a difficultly- separable mixture, Base Z (0.003 %), at first thought to be a single substance.

2. Tigloidine, C₁₃H₂₁O₂N, a syrup, has been shown to be tiglyl-ψ-tropëine, and has been synthesised, as has its geometric isomer, tiglyltropëine. Both these alkaloids are remarkable in possessing hydrobromides which are readily soluble in chloroform, and which can be extracted from aqueous solution by this solvent. Catalytic reduction of them has yielded respectively dl-α-methylbutyryl-ψ-tropëine, and dl-α-methylbutyryltropëine. The hydrobromides of acetyltropëine and acetyl-ψ-tropëine have also been prepared; they are shown to be useful in the identification of tropine and ψ-tropine respectively.

3. Valeroidine, C₁₃H₂₃O₃N, m.p. 85°, [α]²⁰°D -9.0° has been shown to be the monoisovaleryl ester of a dihydroxytropane previously isolated as the dibenzoyl ester by Wolfes and Hromatka (Merck's Jahresber, 1933, 47, 45) from Peruvian coca leaves. The hydrobromide is readily soluble in chloroform, but unlike that of tigloidine, is not extracted from water by this solvent. An attempt has been made to determine the positions of substitution of the hydroxyl groups in the tropane molecule. In the course of this work it has been found that under certain conditions thionyl chloride possesses the remarkable property of demethylating the N-methyl group in valeroidine with production of the secondary base, norvaleroidine, C₁₃H₂₁O₃N. While very stable to oxidation, valeroidine when treated with potassium permanganate in acetone yielded a neutral product, C₁₃H₂₁O₄N which on subsequent treatment with alcoholic hydrochloric acid also gave norvaleroidine. It is hoped to pursue this work.

4. Base Z, C₁₂H₂₁O₂N, a syrup, [α]²⁰°D +2.5° has been shown to be a mixture of about ten parts of poroidine (isovalerylnortropëine) with one part of isoporoidine (d-α-methylbutyrylnortropëine), and has been indirectly racemised. The former constituent was separated by an indirect method, and both have been synthesised; their mixture in the above ratio was shown to be similar to base Z. A probable derivation of these bases from leucine and isoleucine respectively is suggested. Tiglylnortropëine, C₁₂H₁₉O₂N, has also been synthesised. The hydrobromides of the above three alkaloids are readily soluble in chloroform, which solvent also extracts them from aqueous solution. The p-phenylphenacyl esters of the butyric and valeric acids are described. A method for the recovery of acid and alcohol from such esters is also given.

http://hdl.handle.net/1842/35366

The University of Edinburgh

Annexe Thesis Digitisation Project 2019 Block 22

The minor alkaloids of Duboisia myoporoides

Thesis or Dissertation

Doctoral

PhD Doctor of Philosophy