Synthetic Studies in Natural Product Chemistry

McCrindle, Robert (1960) Synthetic Studies in Natural Product Chemistry. PhD thesis, University of Glasgow.

Abstract

I. A stereospecific total synthesis of D-(-)-shikimic acid: The evidence which led to assignment of the structure and absolute stereochemistry of shikimic acid is reviewed. The role of shikimic acid in biosyntnesis is discussed, including its transformation into aromatic amino-acids, lignin and alkaloids, as is its formation from carbohydrates. A synthetic approach to shikimic acid via the dehydroacid corresponding to XXII was unsuccessful. The Diels-Alder adduct (XXXI) of trans-trans-1,4-diacetoxybutadiene and acrylic acid provided the starting point for a successful synthesis. Hydroxylation with osmium tetroxide, isoprepylation and elimination of acetic acid led to (+/-)-shikimic acid which was resolved via the quinine methohydroxy-salt of the corresponding triacetate. II. The catalytic hydrogenation of cyclic anhydrides: Catalytic hydrogenation of the adduct (XXIV) prepared in Part (I) led, in addition to the expected saturated anhydride (XXIX), to the lactol (XXXV), the lactone (XXXVIII) and the acid (XXXIX). A series of anhydrides, chosen to throw light on the influence of structure on the course of hydrogenation, were subjected to catalytic reduction. The three possible products were not obtained in all cases. An attempt is made to rationalise the observed products in terms of the structures of the initial adducts and postulated intermediates. III. Approaches to the total synthesis of diterpenoids:- Published diterpene synthesis are briefly reviewed. Two projected routes to dl-ambreinolide, which is capable of further transformation into the naturally occurring bicyclic diterpenes such as manool, sclareol, cativic acid, and labdanolic acid, are outlined. The first route, based on the condensation of 2-methyl-cyclopentane-1,3-dione with ethyl vinyl ketone, failed when elaboration of the bicyclic enone (CXVI) was attempted. A second approach envisaged the simultaneous formation of rings (A) and (B) by condensation of the vinyl ketone (CXLVI) with the cyclopentanedione. The preparation of this vinyl ketone is recorded.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Organic chemistry
• Date of Award: 1960
• Depositing User: Enlighten Team
• Unique ID: glathesis:1960-79393
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 05 Mar 2020 10:17
• Last Modified: 05 Mar 2020 10:17
• URI: https://theses.gla.ac.uk/id/eprint/79393