Polyketides biomimetic synthesis

Reductive cleavage and hydrolysis of appropriate diisoxazolylmethanes leads to 1,3,5,7-tetraketones, which can be used in the biomimetic synthesis of benzenoid compounds, which are formed in nature by the polyketide pathway. Some of these results are summarized in Table VIII. The synthesis of compounds such as (97) has provided a synthetic equivalent of a 1,3,5,7,9-... 

As mentioned, naphthylisoquinoline alkaloids are structurally unusual on account of the methyl group at the 3-position and oxygenation at the 8- and/or 6-position of the isoquinoline ring which points to a polyketide origin. This postulate has been supported by extensive studies conducted by Btingmann on the in vitro biomimetic synthesis of the naphthalene and isoquinoline portions of these compounds (ref. 13,14) and this work is worth briefly mentioning in a discussion on the total synthesis of these compounds. 

Naidu R (1993) Structure determination and biomimetic synthesis of lichen polyketides. Dissertation, Australian National Univ, Canberra... 

The syntheses of the motif rely generally on strategies mimicking the biosynthetic route in which polyketides are assembled and then cmidensed into a-pyrones and methylated into y-pyrone with methyltransferases (Scheme It is worth noting that a biomimetic synthesis of 1 was actually described by Hertweck in 2008. ... 

In nature, the intramolecular condensation of a 1,3-dicarbonyl moiety with a keto group in polyketides is an important step in the biosynthesis of aromatic compounds. Biomimetic transformations of this type have been intensively investigated by Harris. (For a discussion, see Chapter 1.5, this volume.) In the following, the synthesis of some natural products and biologically active compounds using the Knoevenagel reaction will be described. 

The first synthesis modelled on biomimetic lines was directed to obtaining anacardic acids by way of polyketides [237] and later to a (17 l)-orsellinic acid [43]. A less complicated approach based on the Michael addition of ethyl acetoacetate and ethyl octadec-2-enoate, has led to a C15 orsellinic acid, Fig (4)-56, 2,4-dihydroxy-6n-pentadecylbenzoic, considered to be the biogenetic precursor of the cashew phenols [238], notably cardol, by decarboxylation. The use of bromine at the aromatisation stage in this synthesis precluded the extension of the method to components with unsaturated side-chains, although bromination with copper(ii)bromide and thermal debromination offers an alternative procedure. In a more recent approach, by the use of an oxazole intermediate and its addition to ethyl acetoacetate, (15 0) and (15 1) anacardic acid have been obtained [239] as shown in Scheme 5a, b. The 8(Z),1 l(Z)-diene and 8(Z),1 l(Z),14-triene have also been synthesised [240] by way of ethyl 6-(7-formylheptyl)-2-methoxybenzoate (C), prepared from acyclic sources, rather than, as in previous work, by semisynthesis from the ozonisation of urushiol. 

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