Marine metabolites isolation

A number of rearranged monocyclofarnesyl sesquiterpenoids have been isolated from the sea hare Aplysia dactylomela. These include dactyloxene-A (23), -B (24), and -C (25) and dactylenol (26) together with its acetate.These compounds are related to other marine metabolites isolated from red algae. Aplysistatin (27), a metabolite of the sea hare Aplysia angasi, has been synthesized by a route which involves Hg -mediated brominative cyclization and a novel oxidative debenzylation step (Scheme 6). ... 

Parrain and coworkers described an efficient cascade involving the ring opening of cyclopropene ketal of type 71 followed by CM with a variety of alkenes in the presence of catalyst [Ru]-I for the synthesis of protected divinyl ketones [42]. This sequence was employed by Kozmin and coworkers for the preparation of the linear center portion of bistramide A, a marine metabolite isolated from Lissodinum bistratum which exhibits potent cytotoxicity against several cell lines [43], as well as... 

Carbohydrate derivatives with a spiroisoxazoline moiety, present in psammap-lysins and ceratinamides (metabolites isolated from marine sponges) have been prepared in good yields and excellent regio- and diastereoselectivity by a route involving Wittig olefination and 1,3-dipolar cycloaddition as key steps (477). 

Fig. 2. Number of secondary metabolites isolated especially from marine bacteria until 1999... 

In the mollusks, only marine species are known for unusual metabolites. However, while polypropionates of marine pulmonates have de novo origin (Table 9.1), the secondary metabolites isolated from opisthobranch mollusks derive mostly from dietary cyanobacteria, seaweeds, and invertebrates. 

A number of triterpenoids are bioactive compounds and are used in medicine. For example, fusidic acid is an antimicrobial fungal metabolite, isolated from Fusidium coccineum, and cytotoxic dimeric triterpenoids, crellastatins, are isolated from marine sponges Crella species. 

In this review, data have been presented to illustrate the diversity of organisms living in the sea and the plethora of chemical compounds that have been discovered from them. Since the late 1970s, there has been a veritable explosion of activity and many new marine metabolites have been isolated and identified. Therefore, the present review will cover only recent development in this area. The information was obtained from a review of the scientific literature, and the sources are referenced at the end of the chapter. Bioactive compounds found in marine environments include... 

Bryostatins are a unique family of emerging cancer chemotherapeutic candidates isolated from marine bryozoa [457], They were first discovered in the bryozoan Bugula neritina, but problems with supply of sufficient quantities of this natural product hampered the study of this interesting group of marine metabolites for many years. Although the biochemical basis for their therapeutic activity is not known, these macrolactones exhibit high affinities for PKC isoenzymes, compete for the phorbol ester binding site on PKC and stimulate kinase activity in vivo and in vitro. Bryostatin 1, Fig. (54), one member of this family, is a PKC modulator in a variety of tumor systems [458,459], Bryostatin 1 is currently in phase II... 

Since the discovery of amphimedine by Schmitz and co-workers in 1983 [36], the polycyclic alkaloids based on the pyrido[, /]acridine skeleton have emerged as a well-defined class of marine metabolites, with significant biological activities, isolated from sponges and tunicates [37]. The less common group of sulfide pyridoacridines were only obtained from tunicates and they include the shermilamines, the varamines-lissoclins-diplamine group, and tintamine, another polycyclic alkaloid closely related to them. 

The sulfide marine metabolites having a pyrroloquinoline skeleton can be divided into three groups the batzellines-isobatzellines, the prianosins-discorhabdins, and the makaluvamines. All of these types of compounds have been isolated from sponges. 

The dysideathiazoles (420-424) were also reported from the same sponge and their structures were determined by spectroscopic methods and X-ray analyses [326]. More recently, new variations of this type of unique marine metabolite were obtained. Herbamide A (425) [327] was isolated from a collection of D. herbacea, presumed to be rich in cyanobacteria because of the rich presence of chrorophyll, and barbamide (426) [328] was obtained from the cyanobacterium Lyngbya majuscula. Faulkner and... 

The peptide guanidine derivatives minalemines D-F (459-461), isolated from the New Caledonian tunicate Didemnum rodriguesi, were the first marine metabolites containing a sulfamic acid functional group [354]. Their structures were elucidated through their spectral data and by chemical transformations. 

Small organic molecules such as acylated homoserine lactones have been implicated in gene expression in marine bacteria and in signaling or sensing processes between bacterial communities.28 Structurally related secondary metabolites, e.g., Structures 2.7 and 2.8, have been detected in marine bacterial isolates,2930 where they may be involved in signaling or alternately interfere with this process in competing bacterial strains. 

Isolation and culture of putative symbiotic microorganisms to obtain the bioactive metabolites isolated from the invertebrate-microbe assemblages has been particularly problematic. It has been estimated that only 1% of marine microbes can be isolated and fermented using techniques modified to approximate marine conditions. However, to address this problem, several groups have used differential fractionation or flow cytometric techniques to separate populations of extracellularly associated microorganisms from invertebrate host cells. Chromatographic and spectroscopic analyses of the enriched cell fractions have been used to determine which cell type is producing the compounds. The assumption is that the metabolites are produced in the cell types in which they are detected. 

The methodology described above could be successfully applied for the synthesis of compound 240, containing the core structure of the marine metabolites 225, and 226 starting from N-acetyltryptamine (239). Furthermore, the symmetrical bis(indolyl)nitroethane 236a, as a model structure, could be reduced to the corresponding amine, isolated as its N-acetyl derivative 241 (Scheme 53) [174,177],... 

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