Marine alkaloids derivatives

Huigens RW, Robert III W, Ma LY, Gambino C, Moeller PDR, Basso A, et al. Control of bacterial biofilms with marine alkaloid derivatives. Mol Biosyst 2008 4 (6) 614-21. 

Trabectedin is one of the most important marine alkaloids derived from Ecteinascidia turbinate. It is used as anticancer agent, especially for ovarian cancer treatment. 

As representative of the derivatives of pyridoacridine, eilatin, a marine alkaloid inhibits in vitro cell proliferation in chronic myeloid leukemia patients [244], Other members of the pyridoacridines, such as alkaloids isolated from a Cystodytes sp. ascidian, inhibit topoisomerase II [245], Additionally, analogues derivatives of these type of alkaloids showed interesting anti-HIV activity [246],... 

In an analogous fashion, total synthesis of cytotoxic marine alkaloid, gym-nastatin A (24), which was isolated from the sponge Halicondria japonica, was accomplished via the spirolactol (143) derived from the tyrosinal derivative (142) with PIFA [101] (Scheme 15). 

Kita and co-workers have developed a concise and high-yielding procedure for preparing the pyrroloiminoquinone derivatives (158), which are key precursors of antitumor marine alkaloids, makaluvamine D (54), I (55), and M (56), from the phenol ether derivatives (157) bearing an alkylazido side chain using PIFA-TMSOTf [122] (Scheme 30). 

Pyrrole (1) and indole (2) moieties occur widely in synthetic and natural products, either as a simple structural unit or as part of more complex an-nulated systems [1-9]. The pyrrole derivatives 3 and 4 display antibacterial activity [1-3]. Marine alkaloids ( )-B-norrhazinal (5) and (-)-rhazinilam... 

The marine alkaloid almazole C 112 was synthesised through an iminophosphorane derivative in an aza-Wittig reaction with an acyl chloride 114 <07SL324>. 

The heterocyclic hemi-aminal 44 was formed as a model for the synthesis of the marine alkaloids zoanthamine and zoanthenol and is derived from the cyclic imine formed by the reduction of an appropriated substituted azide <07H(72)213>. A pyrrolidine-fused azepine has been isolated from the venom of the ant Myrmicaria melanogaster and assigned as 45 based upon GC and FT-IR comparison with synthetic material <07JNP160>. The axially chiral doubly bridged biphenyl azepine 46 has been synthesised and used with oxone as an epoxidation catalyst in a biphasic system <070BC501>. 

Another large group of brominated tryptophan-derived marine alkaloids are the aplysinopsins and several new examples have been reported. The sponge Hyrtios erecta has furnished 20 and 21[26], while a New Zealand asddian is the source of kottamides A-E, for example A (22) [27] and E (23) [28], The stony coral Tubastraea sp. contains the structurally complex and unprecedented bisindole tubastrindole A (24) [29]. 

During the total synthesis of the marine alkaloid (+)-lepadiformine by S.M. Weinreb et al., one of the key bicyclic N-acyliminium salt intermediates was subjected to a nucleophilic attack by an organocuprate. ° The resulting allyidimethylsilyl derivative was then treated under the Fieming-Tamao oxidation conditions to afford the corresponding hydroxymethyl compound in excellent yield. 

Directly linked bisoxazole core as a unique feature of hennoxazole A s structure is only found in the polycyclic marine alkaloids diazonamides A-B and cyanobacterium derived muscoride A and hennoxazole A. The marine natural product hennoxazole A was synthesized by a convergent synthesis [1]. 

Weinreb and co-workers made use of a nucleophilic hyroxymethyl equivalent in the synthesis of the marine alkaloid lepadiformine.46 A highly stereoselective addition to a-methoxybenzamide 56 was achieved using the silylmethyl cuprate derived from Grignard reagent 57. Exposure of 58 to Fleming oxidation conditions provided 59 in high yield. 

Lepadins constitute a class of recently discovered antimalarial marine alkaloids. These molecules are decahydroquinoline derivatives bearing a linear eight-carbon chain isolated from two marine invertebrates of Australian origin, Clavelina lepadiformis [49] and Didemnum sp. [50]. 

The excellent reviews of Berlinck [1-5] have surveyed a great number of guanidine-type natural products. In addition, some guanidine-derived marine alkaloids have been reviewed by Kobayashi and Ishibashi [6,7]. Also, a recent book gave accounts of marine alkaloids including the phakellins, palau amines and oroidin-like dimers derived from bromopyrroles and polyketide-derived polycyclic guanidine alkaloids [8]. 

In the 1980s Muratake and Natsume (202) in a number of reports presented a new, interesting approach to the synthesis of substituted indole derivatives that focused on their use as intermediates in the preparation of a variety of clavine alkaloids and mycotoxins. The method elaborated by the authors consisted of constructing the specifically substituted benzene portion of the indole nucleus, with 1-methoxycarbonylpyrrole being the starting material. The functionalized 4-alkylindole thus obtained was transformed to a tricyclic indole derivative which appeared to be a common intermediate for the synthesis of several ergot alkaloids, as exemplified by the synthesis of ( )-dihydrosetoclavine (203-205) (Scheme 42). Recently, the application of this method was extended by the authors (206) to the syntheses of a series of marine alkaloids, the hapalindoles. Most of these alkaloids have a tetracyclic framework made up of 3,4-substituted tryptamine and two isoprene units. 

A similar intramolecular cyclization of 3-(azidoethyl)indole derivatives 309 provides an efficient route to the pyrroloiminoquinone system 310 (Scheme 3.127), which is an essential component of several recently isolated marine alkaloids such as makaluvamines, isobatzelline C and discorhabdins, which possess potent biological activities [372]. 

From the point of view of biological activity, it is possible to divide alkaloids into (1) neutral or weakly basic molecules (e.g., lactams such as rici-nine, certain N-oxides such as indicine), (2) animal-derived alkaloids (e.g., anuran, mammalian and arthropod alkaloids), (3) marine alkaloids, (4) moss alkaloids, (5) fungal and bacterial alkaloids, and (6) nonnatural alkaloids (structurally modified or analogues). 

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