Polyenoyltetramic acids

Oleficin (74), a polyenoyltetramic acid characterised by the presence of the desoxy sugar D-digitoxose on the C-3 hexenoyl side chain, is an antibiotic isolated from a strain related to Streptomyces parvulus [130]. 

Synthesis of physarorubinic acid, which is a polyenoyltetramic acid plasmodial pigment, is another example. The synthesis uses a Lacey-Dieckmann cyclization starting with ester 51, followed by deprotection to give physarorubinic acid (52) in 78% yield for the two steps. ... 

FIG. 2 Acyltetramic acids (4) and their enoyl- (5) and polyenoyltetramic acid (6) counterparts. The favored tautomers of these compounds do not contain acyl, enoyl, or polyenoyl moieties. The actual substituents are hydroxymethyUdene, a-hydroxyalkylidene, and (a-hydroxyalk-2-en)ylidene or (a-hydroxyaIka-2,4-dien)ylidene or (a-hydroxyalka-2,4,6-trien)ylidene, etc., respectively. 

FIG. 3 The polyenoyltetramic acid antibiotic a-lipomycin (7) and its aglycon P-lipomycin (8). The (stereo)structures of these compounds are depicted as formulated before our syntheses were accomplished. How the information shown here was gained is detailed in Section 3.1. The asterisks designate stereocenters with previously unknown configurations. 

The most frequently used strategy for making acyl- and polyenoyltetramic acids is by the Lacey-Dieckmann cyclization of p-ketoamides, whose nitrogen... 

Altogether, we developed a new western building block for synthesizing poly-enoyltetramic acids. We demonstrated its usefulness in accomplishing total syntheses of the polyenoyltetramic acid natural products a-lipomycin (7) and p-lipomycin (8). We identified the configurations of the previously unassigned stereocenters of both compounds as AR and 155. We might have considered these deductions reasonably safe. However, we preferred absolute... 

Synthesizing the chain-extended multiply unsaturated co-bromo- or (D-iodo-fi-ketoamide seco-tetramic acid precursors 42-44a, b, c, etc. depicted in Fig. 8 and utilizing them for polyenoyltetramic acid synthesis. 

Studying the polyenoyltetramic acid natural products altamycin (120) and oleficin (122) (Fig. 17) both by the degradation and the synthesis techniques developed in the current work. The configuration of two stereocenters in each compound, which have not yet been assigned, would thereby be clarified. 

FIG. 17 Total synthesis and the elucidation of stereostructure—renewable challenges. The polyenoyltetramic acids (—)-altamycin and (—)-oleficin as desirable objects of study. 

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