Pyrones aldol cyclization

The 5,6-dihydro-a-pyrone ring is present in several biologically active molecules697,698. This ring system may be usefully prepared, in a one-pot procedure, via a directed aldol-type condensation followed by cyclization (equation 194)6". The products are usefully functionalized with a carboxylic ester group in the 3-position which allows further synthetic elaboration. 

Phenols add intramolecularly to Michael acceptors.536- 540 Under acidic conditions, a one-pot sequence starts with initial electrophilic acetylation of the activated aromatic ring and is followed by cyclizalion.536 537 With an appropriate leaving group in the /1-position (OMe,537 NH2,539-s4° or other amines such as in 3538) the unsaturated carbonyl compound (e.g., 4) is formed. Other approaches to pyrones include the self-condensation of protected /1-hydroxy acrylates,541 intramolecular aldol reactions followed by condensation,542,543 thermal cycli-zations of unsaturated h-chloro esters,544 and an iodo-cyclization-elimination sequence with Michael acceptors.545 Oxymercuration of an unsaturated alcohol is an alternative cyclization approach to tetrahydropyrans.442... 

In the synthesis of zincophorin, two cyclocondensation reactions are also used. In the first cyclocondensation reaction, trimethylsilyloxy diene (14) reacts with aldehyde (193) using anhydrous MgBr2 as the catalyst to give the anti-ACF pyrone (194) in 80% yield (Scheme 53). The syn.anti ratio in this reaction is 7 1. After a series of standard manipulations aldehyde (19< ) is obtained. In the second cyclocondensation reaction, anti-CF pyrone (197) results from reaction of the (4 )-r-butyidimethylsilyloxy diene (195) with aldehyde (19< ) under BF3-OEt2 catalysis (197) and its syn-CF isomers are obtained in a ratio of 4 1 and overall yield of 68%. The anti-CF aldol product is purified and cyclized to anti-CF pyrone (197) in benzene using pyridinium p-toluenesulfonate as a catalyst. Pyrone (197) converted into zincophorin (198) by a sequence of steps shown in Scheme 52. 

The next major enzyme in the series, p-coumarate CoA ligase, was first isolated from illuminated cell suspension cultures of Petroselinum crispum (syn. P. hortense) and shown to be specifically related to flavonoid and stilbene biosynthesis. The enzyme requires p-coumaric acid, CoASH, ATP, and Mg for activity (Hahlbrock, 1981 Hutchinson, 1986). Three malonyl-CoA units are added and cyclized via a Claisen condensation (see Chapter 5) to produce a chalcone intermediate (9). Condensation of the same intermediates via an aldol condensation yields pyrones and... 

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