Resorcinylic macrolides

The resorcinylic macrolides (also known as resordnylic add lactones or RALs) are a family of naturally occurring homologous macrolides. They are derived from polyketide biogenesis in different fungi and have been isolated from different fungal strains [12]. They have unique chemical structures and potent biological activities (antitumoral, antibiotic, and antimalarial activities) [13]. 

The syntheses of radicicol (3) are based on RCM of a diene-ene system, which avoids the problem of regioselectivity, compatibility with labile groups such as a vinyl epoxide, the dithiane protecting group, and the /Z selectivity [14]. In these 

5 Synthesis of Natural Products Containing Macrocycles by Alkene Ring-closing Metathesis 

One closely related family to resorcinylic macroHdes are the saUcylate enamide macrolides, which are secondary marine metabolites with a 12-membered ring benzolactone and a dienyl enamide side chain. SaHcyhhalamide A (34) is a potent inhibitor of the mammalian vacuolar ATPase and exerts great diSerential cytotoxicity in the National Cancer Institute (NCI) 60 ceU lines [23]. Other members 

However, the synthesis of 34 has been the subject of many efforts in order to obtain a good ( /Z) stereoselectivity and deserve some comments (Table 5.1). The remote phenolic hydroxy group is of importance as it favors the undesired 

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Yang ZQ, Ceng X, Solit D, Pratilas CA, Rosen N, Danishefsky SJ, New efficient synthesis of resorcinylic macrolides via ynolides Establishment of cycloproparadi-cicol as synthetically feasible preclinical anticancer agent based on Hsp90 as the target,/Am Chem Soc 126 7881-7889, 2004. 

Resorcinylic macrolides are a family of natural products that possess a 14-membered macrolide core with a fused benzenoid subunit. A member of this family that has drawn significant scientific attention due to its antimalarial and cytotoxic activity is aigialomycin D. In one total synthesis of aigialomydn D, late-stage nickel-catalyzed macrocyclization was employed to afford the macrocyclic core [43]. Macrolide precursor 45 was cyclized in 61% yield in a 1 1 diastereoselectivity. Subsequent global deprotection and HPLC purification afforded aigialomycin D and the allylic alcohol epimer in 90% overall yield (Scheme 8.45). 

A similar procedure was used for the total synthesis of resorcinylic macrolides such as pochonin C (42, Figure 24.2). Porco and Wang reported on the first example of a successful diene-diene RCM for the synthesis of the... 

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