Acetogenin derivatives

Acetogenin derivatives Annona cherimola SiOj CHCI3 - MeOH Kedde s reagent Identification 62 0 CfQ... 

Another dictyotalean genus, Dictyopteris, has been reported to produce an array of Cu cyclic or acyclic acetogenins derived from higher fatty acids (Stratmann et al. 1992). Examples include the hydrocarbons dictyopterene A (Fig. 1.6e) (Moore et al. 1968) and dictyopterene D [B1] (Fig. 1.6f) (Moore and Pettus 1971), which act as pheromones in sexual reproduction (Stratmann et al. 1992). The compounds are short lived and undergo facile degradative oxidation to yield compounds such as dictyoprolene (Fig. 1.6g) (Yamada et al. 1979) and dihydrotropone (Fig. 1.6h) (Moore and Yost 1973). In a tme exhibition of efficiency, these degradative products have also been shown to act as a chemical defense (Hay et al. 1998). 

Figure 4. Two Acetogenin Derivatives, 9 and 10. with Single Crystal, X-ray Structures.

ABSTRACT Marine invertebrates such as ascidians, sponges and others are a prolific source of bioactive secondary metabolites. We have isolated a variety of marine natural products from the Okinawan marine invertebrates by using the sea urchin egg assay. Our recent work, the isolation, structure determination and activities of chlorinated macrolides, sesterterpenic acids, a bromotyrosine derivative, acetogenin derived endoperoxides, diterpene alkaloids, sesquiterpene quinones and spiro-sesquiterpenes, is presented in this article. The syntheses of these metabolites are also described. 

Since a detailed study of these unique inhibitors might provide new insight into the terminal electron transfer step of the enzyme, we further characterized their inhibitory action using the most potent Alac-acetogenin derivative (compound 1). Unlike ordinary Complex I inhibitors, 1 has a dose-response curve for inhibition of the reduction of exogenous short-chain ubiquinones that was difficult to... 

Rieser MJ, Kozlowski JF, Wood KV, McLaughlin JL. Muri-catacin a simple biologically active acetogenin derivative from the seeds annora muricata (annonaceae). Tetrahedron Lett. 1991 32(9) 1137-1140. 

Figadere B, Harmange J-C, Laurens A, Cave A. Stereospecific synthesis of (-I-) muricatacin a biologically active acetogenin derivative. Tetrahedron Lett. 1991 32(51) 7539-7542. 

Stereoselective intramolecular oxymercuration of carbohydrate derivatives was proposed as the key reaction for efficient preparation of mono- and dihydroxylated unsymmetrical bis-tetrahydrofuran skeletons present in naturally occurring biologically active acetogenins. The trans- and. mz-selective intramolecular oxymercurations were explored in an enantioselective synthesis of the bis-tetrahydrofuran skeleton of mucoxin (Fig. 57).73... 

The majority of natural products from tropical macroalgae are terpenoids (mainly sesqui- and diterpenoids), followed by acetogenins (acetate-derived compounds), and metabolites of mixed biosynthetic origin (such as meroditerpenes), frequently composed of terpenoid and aromatic portions (Blunt et al. 2007 and previous reviews see Chap. 1). 

The other acetogenins, shown in Table II, are a varied assortment of small molecule compounds which as a group contain alkene, alcohol, and carbonyl (acid, ester, aldehyde, and ketone) functionality. They are fairly typical substances with common structural features. Again, those compounds possessing an odd number of carbon atoms are less common, and biogenetlcally may be derived from a propionate starter unit. 

FIGURE 33. Constitution formula of the acetogenin oxanthromicin (79) and its tetramethyl derivative 80 ... 

Solanaceae), acts as competitive inhibitor for ubiquinone in Complex I. Methyl capsaicin is more potent than capsaicin, indicating that the phenolic OH is not essential for the activity [297]. Other natural inhibitors of Complex I are annonaceous acetogenins. These compounds belong to a wide group of natural products isolated from several species of the Annonaceae family, which include more than 250 molecules with diverse chemical structures. Among the various classes, it seems that monotetrahydrofuranic derivatives are less potent than other acetogenins [296, 299]. 

The Annonaceous acetogenins are an important new group of long-chain fatty acid derivatives found exclusively in the plant family, Annonaceae. Nearly 400 compounds from this... 

Normal-phase HPLC (NP-HPLC) and reverse-phase HPLC (RP-HPLC) are used to purify the final products of these chemical derivatives. For NP-HPLC a gradient of hex-ane/MeOH/THF works well for separations. Usually, acetogenins are placed on RP-HPLC because they are more easily detected in the low-ultraviolet range. The weak UV absorbance at 210 nm for the a,p-unsaturated y-lactone is one reason to use an RP-HPLC system. This weak absorbance is often overshadowed by impurities that have larger absorbances. Another reason for choosing RP-HPLC is because the solvent cutoff for the RP solvents is lower than NP solvents. In their pure form, acetogenins are white, waxy substances. 

Collie s hypothesis that aromatic compounds are made biologically from ethanoic acid was greatly expanded by A. J. Birch to include an extraordinary number of diverse compounds. The generic name acetogenin has been suggested as a convenient classification for ethanoate (acetate)-derived natural products, but the name polyketides also is used. Naturally occurring aromatic compounds and quinones are largely made in this way. An example is 2-hydroxy-6-methylbenzoic acid formed as a metabolite of the mold Penicillium urticae ... 

As presented in Table 1.2, over half of reported marine natural products are derived from the isoprenoid biosynthetic pathway (56%), with the remainder split mainly between amino acid (19%) and acetogenin (20%) pathways. Secondary metabolites falling into the categories of nucleic acids and carbohydrates comprise only 1%. Such low levels are somewhat surprising given the fundamental importance of such classes of compounds as primary metabolites. 

Metabolites of the phylum Porifera account for almost 50% of the natural products reported from marine invertebrates. Of the 2609 poriferan metabolites, 98% are derived from amino acid, acetogenin, or isoprenoid pathways. Isoprenoids account for 50% of all sponge metabolites, while amino acid and polyketide pathways account for 26% and 22%, respectively. A significant number of sponge metabolites appear to be derived from mixed biosynthetic pathways. Most structures reported containing carbohydrate moieties were glycosides. 

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