Other Polyketides

Other macrocyclic compounds presumably of polyketide origin such as okilac-tomycin (136) and terpestacin (139), both possessing antitumoral activity, were 

Latrunculins A (272) and B (273) are two fish toxins first isolated from the Red Sea sponge Latrunculia magnifica (220,221). Two minor toxins named latrunculins C (274) and D (275) were isolated from the same sponge (222). Latrunculin A (272) was isolated from the Pacific nudibranch Chro-modoris elisabethina (223), and latrunculin B (273) was obtained from a nudibranch Glossodoris quadricolor (224) these nudibranchs are known 

The Okinawan tunicate Eudistoma cf. rigida contained novel nitrogen-containing macrolides, namely, iejimalides A (276) and B (277) which show potent cytotoxicity against murine leukemia cells (227). Iejimalides possess a unique structure with AMormyl-L-serine in the side chain and are the first macrolides isolated from a tunicate. 

Mycalamides A (286) (233) and B (287) 234) were isolated from a New Zealand sponge of the genus Mycale and exhibit significant in vivo antiviral and antitumor activity. From an Okinawan sponge Theonella sp.) onna-mide A (288) with a structure closely related to mycalamides was isolated, 

Bistramide A (C H Og) was isolated from the tunicate Lissoclinum bistratum collected at New Caledonia and shown to possess neuro- and cytotoxic activity. Although extensive two-dimensional NMR studies were used, its complete structure remains to be established (238). 

Two epimeric amino alcohols, 2(5)-aminotetradeca-5,7-dien-3(5)- and -3(/ )-ol (305 and 306) were isolated from a sponge from Papua New Guinea (Xestospongia sp.) (248). The absolute stereochemistry was disclosed by degradation to L-alanine, and these amino alcohols (305 and 306) were suggested to be biosynthesized from fatty acids and alanine. Compounds 305 and 306 show antimicrobial activity. Rhizochalin (307) was isolated from the Madagascan sponge Rhizochalina incrustata as an antimicrobial constituent (349). The biosynthetic pathway for 307 is unknown but is conventionally believed to be derived from alanine and a polyketide precursors). 

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Figure 21-9 Postulated origin of orsellinic acid and other polyketides.

J Beck, S Ripka, A Siegner, E Schiltz, E Schweizer. The multifunctional 6-methyl-salicylic acid synthase gene of Penicillium patuhmv. its gene structure relative to that of other polyketide synthases. Eur J Biochem 192 487-498, 1990. 

Substituted 5-methylene-l,3-dk>xepines 38 are converted into vinyl acetals 39 by Ni catalysts bearing (R,R)-DuPHOS or (R,R)-ChiraPHOS as chiral ligands (Scheme 11) [16]. Similarly high enantioselectivity can be achieved with 5-methyl-ene-l,3-dioxanes as substrates [17]. Chiral Ru-catalysts are less efficient [18]. Cyclic acetals obtained are an useful starting material for preparation of macrolide antibiotics and other polyketide-derived natural products. 

Fatty acids and other polyketides are made from acetyl CoA... 

The modular organization of this and other polyketide-synthases and the composition in defined domains of enzymatic activity allows the inactivation, the deletion (loss of function), the enlargement (gain of function) and the exchange of separate enzymatic units through genetic manipulation of polyketide-synthase genes. 

As shown below, the attack of epoxide 6 with lithium dimethylcuprate is a key step of Hanessian et al. s erythronolide synthesis [23]. This methodology was also applied to the preparation of other polyketide-derived macrolides. Specific to erythronolide, introduction of the methyl group at C2 was achieved according to Scheme 11.3. 

D-alanine residue. Other polyketides which contain such an arrangement are the trienomycins [99], while similar CHC chain terminating (synthase starter) units are found in a branch of asukamycin [96], and in the eo-cyclohexyl fatty acids of certain thermophilic bacteria [100] substituted CHCs are also found as PKS starter units in the rapamycin family of polyketides (see Sect. 8). The cyclohexyl moieties of these compounds have been demonstrated to derive from the shiki-mate pathway. 

The combination of a root hair specific EST approach and expression analysis was an effective strategy for isolating candidate polyketide synthases potentially involved in sorgoleone biosynthesis. As a result of these efforts, two novel type III polyketide synthases have been identified that preferentially use long chain acyl Co-A s and are potentially involved in sorgoleone biosynthesis. These candidate polyketide synthases can form pentadecatriene resorcinol, an intermediate in sorgoleone biosynthesis. Furthermore, these efforts may aid in the identification of other polyketide synthases responsible for the biosynthesis of phenolic lipids in other plant species. 

A unique asynunetric isomerization of 2-substituted 5-methylene-l,3-diox-anes 22 to 5-methyl-4H-l,3-dioxins 23 was catalyzed by a ruthenium complex of DIOP under a hydrogen atmosphere (Scheme 3). Although the enantiomeric purity remained in the range of 35 to 50%, cyclic acetals obtained are promising starting materials for the synthesis of macrolide antibiotics and other polyketide-derived natural products [30]. 

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