Polyenal macrolides biological activity

Sato/Kaneko [104] and Carreira [105] have independently employed acetoacetate-derived O-silyl dienolates as Si-substituted nucleophiles in asymmetric catalytic aldol reactions. The aldol products, d-hydroxy-/3-ketoesters, and the derived syn- and anti-yS,d-diol esters are ubiquitous structural subunits in biologically active natural products such as the polyene macrolide antibiotics. These structural subunits are also found in chemotherapeutics, most notably compactin analogs [106] that have been studied as... 

In recent years, much effort has been spent trying to determine the absolute configuration of the many polyene macrolide asymmetric centers, using well-established enantioselective organic transformations and advanced spectroscopic studies. This work is a necessary prelude to any accurate chemical modification, conformational analysis related to biological activity and, of course, attempt to totally synthesize a given antibiotic or analogue. 

The catalytic version of this type of reaction was realized by using acetoacetate derived O-silyl dienolate as nucleophiles in the presence of Carreira s catalyst, giving acetoacetate y-adducts in high yields and enantiomeric excesses [119] (Scheme 14.42). The products are ubiquitous structural subunits in biologically active natural products such as the polyene macrolide antibiotic and medicinally important HMG-CoA reductase inhibitors. This aldol addition can also be catalyzed by BINOL-Ti complex in the presence of 4A MS with moderate to good enantioselectivity [120]. The same catalyst system was also efficient in the asymmetric aldol reaction between the aldehydes and Chan s diene [ 1,3-bis-(trimethylsilyloxy)-l-methoxy-buta-1,3-diene] and other related silyl enol ethers [121, 122] (Scheme 14.43) or the functionalized silyl enol ether such as 2-(trimethylsilyloxy)furan with good to excellent enantioselectivities [123]. 

The comparative chemotherapeutic activities of several heptaene macrolide antibiotics, including amphotericin B, have been examined, and some biological properties of polyene macrolide ester salts have been reported. ... 

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