Polymalonate

The fatty acid pathway or, as we should call it now, the acyl polymalonate pathway, also gives rise to an inexhaustible variety of aromatic and other compounds belonging to the family of the polyketides. You saw in Chapter 50 how the shikimic acid pathway makes aromatic compounds but the compounds below are from the polyketide route. 

Merely by writing ketones instead of phenols and doing one disconnection corresponding to a simple carbonyl condensation, we have reached a possible starting material which is a typical acyl polymalonate product without any reductions. This is what polyketides are. The fatty acids are assembled with full reduction at each stage. Polyketides are assembled from the same process but without full reduction indeed, as the name polyketide suggests, many are made without any reduction at all. This is the biosynthesis of orsellinic acid. 

This precise sequence was discovered only through very careful double labelling experiments and after the discovery of specific inhibitors for the enzyme. Since polyketides can be made from the acyl polymalonate pathway with or without reduction and elimination at any step, the number of possible structures is vast. With more reduction, no aromatic ring can be formed macrolide antibiotics such as brefeldin A come from this route. 

In the chapter we suggested that you could detect an acetate starter unit and seven malonate additional units in the skeleton of brefeldin. Give the mechanism of the addition of the first malonyl CoA unit to acetate. Draw out the structure of the complete acyl polymalonate chain and state dearly what must happen to each section of it (reduction, elimination, etc.) to get brefeldin A. 

Olivetol has the characteristic 1,3-diOH pattern of a polyketide around the benzene ring but it has only 11 carbon atoms so CO2 was probably lost somewhere and the long side chain has certainly been reduced. The acyl-polymalonate pathway (pp. 1425-36) needs to be used. We start from... 

The plant families Ancistrocladaceae and Dioncophyllaceae are the only identifled sources of the unusual naphthylisoquinoline alkaloids (ref. 1). The family Ancistrocladaceae contains one genus, Ancistrocladus, which consists of approximately 20 species that are distributed in the Indian archipelago, tropical Asia and tropical West Africa. These isoquinoline alkaloids are structurally unique in that they appear to originate, biosynthetically, form the acetate-polymalonate pathway and not from amino acids (ref. 1). Another interesting structural feature of these compounds is that they exist as thermally stable atropisomers because of restricted rotation about the biaryl linkage. 

Figure 4. Comparison of a combined main-chain/side-chain polyester with the corresponding main-chain and side-group polymalonates. Ar c, the temperature range of the LC phase.

Combined SmC LCPs were particularly studied in the late 1980s, mainly by the Mainz group [58-61], They all derive from a substituted polymalonate obtained by step-growth polymerization (Fig. 8). The occurrence of SmC with broad temperature ranges was quite easily obtained with this class of compound. It seems that combined polymers are still prepared to obtain SmC elastomers [62]. 

The six-carbon moiety attached to C-15 in verrol and the trichoverrins is mevalonate-derived 248), and after cyclisation to form the macrolide, the 2 -ene can undergo hydrogenation, a-epoxidation, or hydration. The ethylenic double bonds in the acetate-polymalonate-derived eight-carbon moiety attached to C-4 in the trichoverroids occur as Z or E (see Table 1), but are always 7 (E), 9 (Z) in the macrolide. 

CM is also very useful if the objective is to modify branched polymers or to introduce some convenient functional groups. This was the case of two original studies conducted by the Meier s research team. The first study [26] described the reaction of a poly(2-oxazoline) containing terminal double bonds in the side chains with various functional acrylates in the presence of a HG-II. The second (more recent) study [27] involved the synthesis of a polymalonate bearing C9 aliphatic side chains with terminal double bonds used for grafting-onto reactions by ruthenium-catalysed CM. 

Kolb and Meier [43] prepared a malonate derivative of methyl 10-undecenoate, which was polymerised further with 1,6-hexanediol using titanium (IV) isopropoxide as a catalyst. This polymalonate, bearing a C9 aliphatic side chain with terminal double bonds, was then subjected to grafting by ruthenium-catalysed cross-metathesis reactions with acrylates or thiol-ene addition reactions. This functionalisation enabled a subsequent Passerini multi-component reaction [44] using the pendant carboxylic-acid moiety of the modified polymers that resulted from the thiol-ene addition of 3-mercaptopropionic acid into the initial double bonds of the polymer. 

Lichen secondary metabolites are derived from three chemical pathways acetate-polymalonate pathway, shikimic acid pathway and mevalonic acid pathway (Fig. 1.3). 

Acetate-polymalonate pathway includes the most common lichen compounds such as... 

Lichen Secondary Metabolites of the Acetate-Polymalonate Pathway... 

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