Marine antitumor antibiotics

In another recent development in aromatic synthesis, the Bergman cydization [7] is beginning to be exploited for preparative purposes. This process has been studied for many years because of its importance with regard to the biological action of several marine antitumor antibiotics such as calicheamicin [58] and because of its interesting reaction mechanism [8]. Now, more and more synthetic applications are beginning to be reported in the literature [59]. 

In 1997 (-)-callystatin A (Fig. 1.2.2), a potent cytotoxic polyketide, was isolated from the marine sponge Callyspongia truncata and structurally elucidated by Ko-bayashi et al. [20] shortly afterward its absolute configuration was confirmed by the same authors by total synthesis [21]. The structure of (-)-callystatin A shows a polypropionate chain and a lactone ring connected to each other by two diene systems separated by two sp carbon atoms (Fig. 1.2.2). Since this arrangement is structurally related to several antitumor antibiotics and due to the fact that only very small amounts can be isolated from natural sources, callistatin A has been... 

McDonald LA, Abbanat DR, Barbieri LR, Beman VS, Discafani CM, Greenstein M, Janota K, Korshalla JD, Lassota P, Tischler M, Carter GT (1999) Spiroxins, DNA Cleaving Antitumor Antibiotics from a Marine-Derived Fungus. Tetrahedron Lett 40 2489... 

Kwon, H. C., Kauffman, C. A., Jensen, P. R., Fenical, W. Marinomycins A-D, antitumor-antibiotics of a new structure class from a marine actinomycete of the recently discovered genus Marinispora . J. Am. Chem. Soc. 2006,128, 1622-1632. 

Polypropionate chains with alternating methyl and hydroxy substituents are structural elements of many natural products with a broad spectrum of biological activities (e.g. antibiotic, antitumor). The anti-anti stereotriad is symmetric but is the most elusive one. Harada and Oku described the synthesis and the chemical desymmetrization of meso-polypropionates [152]. More recently, the problem of enantiotopic group differentiation was solved by enzymatic transesterification. The synthesis of the acid moiety of the marine polypropionate dolabriferol (Figure 6.58a) and the elaboration of the C(19)-C(27) segment of the antibiotic rifamycin S (Figure 6.58b) involved desymmetrization of meso-polypropionates [153,154]. 

Baz, J. Canedo, L.M. Fernandez Puentes, J.L. (1997) Thiocoraline, a new depsipeptide with antitumor activity produced by a marine Micromonospora. J. Antibiot., 50, 738-41. 

N-Alkylation is an important modification of the peptide bond. In particular, N-methylation is widespread and commonly occurs in natural peptides from plants, marine sources, and various microorganisms. Several of these compounds have important biological activity, such as antibiotic (e.g., enniatins, 1 monamycins, 2 echinomycin 3 ), antitumor (e.g., bouvardin, 4 dolastatin 56 ) and immunosuppressor activity (e.g., cyclosporin 7 ). For reviews see refs 8-10. ... 

Although historically most useful antibiotics have come from spore forming microorganisms, marine organisms have yielded the candidate antitumor peptide dideinnin B and cytostatic peptides such as the patellamides. Many of the marine peptides have little or no antimicrobial... 

Stereoselective total syntheses of Zincophorin, the ionofore antibiotic (substituted tetrahydropyrane), and Scytophycin C, an antitumor marine macrolide 04YGK1080. 

Although historically most useful antibiotics have come from spore forming microorganisms, marine organisms have yielded the candidate antitumor peptide didemnin B [77327-50-0] (2) and cytostatic peptides such as the patellamides (3). Many of the marine peptides have little or no antimicrobial activity. Antibacterial peptides called magainins are found in frog skin (4) and antibacterial proteins called defensins are found in mammalian white blood cells (5). The commercially important insecticidal proteins from Bacillus thuringensis (6) are not discussed herein nor are the numerous peptide siderophores (7,8), which, except for the albomycins (9), are usually not antimicrobial. 

Anthraqrclines without substituents in ring A are rare and not more than ten are known. 4-Deoxyauramycinone (25a) was isolated from Streptomyces galilaeus in 1983 [27,28] and re-isolated from a marine-derived Streptomyces strain [29]. Antibiotic and antitumor activities were reported, although the biological activities of the aglycones are usually neghgible. 

Phenazine natural products are isolated as secondary metabolites primarily from Pseudomonas, Strep-tomyces, and a few other genera from soil or marine habitats. The biological properties of this class of natural products include antibiotic, antitumor, antimalaria, and antiparasitic activities. The role of phenazine pigments as antibiotics and virulence factors has been briefly reviewed recently, and the biochemistry of phenazine production was reviewed in 1986.8... 

Thiazoles occupy a prominent position among heterocycles. Many of them obtained from microbial and marine origins exhibit important biological effects such as antitumor, antifungal, antibiotic, and antiviral activities. Synthetic thiazoles exhib-... 

Outstanding properties Marine polyacetylenes constitute a very structurally diverse and useful class of compounds with Important biological activities such as antifungal, antibiotic, anticancer, antitumor, antl-HIV, anti-inflammatory, and antimicrobial properties. Legrave, N Elsebal, M F Mehirl, M Amade, P, Studies in Naturai Products Chemistry, Chapter 8, 251-95, Eisevier,2015. 

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