Antiviral marine natural product

The total synthesis of the antiviral marine natural product (-)-hennoxazole A was accomplished by F. Yokokawa and co-workers." The mild reduction of a secondary alkyl azide at C9 was carried out using triphenylphosphine in a THF/water mixture at slightly elevated temperature. The corresponding primary amine was obtained in good yield and was subsequently acylated and converted to one of the oxazole rings of the natural product. 

The antiviral marine natural product, (-)-hennoxazole A, was synthesized in the laboratory of F. Yokokawa." The highly functionalized tetrahydropyranyl ring moiety was prepared by the sequence of a Mukaiyama aldol reaction, cheiation-controiied 1,3-syn reduction, Wacker oxidation, and an acid catalyzed intramolecular ketalization. The terminal olefin functionality was oxidized by the modified Wacker oxidation, which utilized Cu(OAc)2 as a co-oxidant. Interestingly, a similar terminal alkene substrate, which had an oxazole moiety, failed to undergo oxidation to the corresponding methyl ketone under a variety of conditions. 

Yokokawa, F., Asano, T., Shioih, T. Total Synthesis of the Antiviral Marine Natural Product (-)-Hennoxazole A. Org. Lett. 2000, 2, 4169-4172. 

The antiviral marine natural product 93, [( )-hennoxazo e A] is synthesized by a convergent approach and the final step includes the coupling of oxazole carboxylic acid (95) and pyran derivative (94) using DEPC.36,37 Hennoxazole A is active against herpes with peripheral analgesic activity comparable to that of indomethacin. 

Smith employed a [2,3]-Wittig-Still rearrangement to install the trisubstituted (Z)-20-double bond in his group s total S5mthesis of (-)-hennoxazole A (100), an antiviral marine natural product. The transition state conformation 101a is similar to the ground state due to strain fScheme 17.161. 

Similar results have been obtained in the coupling of aldehyde 35 and enol silane 36, which resulted in a 9 1 ratio of diastereomers favoring 37, a key intermediate in the synthesis of the antiviral marine natural product (-)-hennoxazole. " In a similar manner, coupling of 38 and 39 resulted in 40, providing an alternate route to the same molecule. 

Nakagawa, M., Liu, J., and Hino, T. (1990) Total synthesis of antiviral marine natural products, eudistomins. J. Synth. Org. Chem. Jpn. 48, 891-906 Chem. Abstr., 114,102471u. 

Entries 10 and 11 are examples of reactions involving thermal generation of quinodimethanes. In Entry 12 a quinodimethane is generated by photoenolization and used in conjunction with an IMDA reaction to create the carbon skeleton found in the hamigerans, which are marine natural products having antiviral activity. 

The extraordinary biomedical potential of marine natural products is well documented 4 6 recent reviews provide details of their cytotoxic,7-8 antiviral,9 antiparasitic,10 and antimalarial11 activities. In addition, numerous marine metabolites show useful antimicrobial activity. Although some of... 

Other marine natural products with potent antitumour and antiviral activities, the eudistomins, continue to attract attention. As part of a new synthetic approach to the eudistomins, the stereoselective formation of the P-lactam fused oxathiazepine 110 has been reported <03SL738> C-N bond formation from 106 (via 105) was used to complete the seven-membered ring, and then this product 107 was converted into 110 via 108 and 109. Unfortunately, after ring opening the P-lactam in 110 and setting up the substituents for indole ring formation, this crucial indolisation was not successful. Other pathways are being explored but the P-lactam precursor concept is a clever one. 

Although the marine environment is a plentiful source of interesting new products with pharmaceutical potential, only a few of these marine natural products have reached the stage of commercial production. Arabinofuranosyladenine (ara-A, isolated from the Gorgonian Eunicella cavolini) [210] is the unique marine secondary metabolite currently in clinical use and is one of most potent antiviral drugs [211]. The second one is avarol, a sesquiterpene hydroquinone isolated from the sponge... 

Benzoylpedamide (140) has been employed successfully in the total synthesis of ( + )-pederin (654) [150]. In addition, intermediate 649 has been used in the synthesis of the right half (655) of mycalamide A (656), a structurally related marine natural product possessing antiviral and antitumor activity [151]. 

Many polycyclic natural compounds that contain bromine atoms have been isolated from several different marine organisms (Fig. 9.3) [7, 8]. Most of them possess bioactivities of pharmacological interest such as antibacterial, anticancer, antifungal, anti-inflammatory, and antiviral activities. Natural products that have an a-bromo-p,p-dimethylcyclohexane structure are also bioactive compounds. Their biosynthesis... 

The acid rearrangement of the epoxy ester moiety of 12 (Fig. 25.1) is the key step in the synthesis of orthoesterol B, a marine natural product with antiviral activity. Based on the meehanism proposed for the formation of 4 formulate the strueture of flie orflioester fliat should be obtained in the rearrangement of 12. Interestingly, when diastereomer 13 was treated under the same eonditions, it remained unaltered for months. Could you explain why ... 

Laille, M., Gerald, F., and Debitus, C. (1998) In vitro antiviral activity on dengue virus of marine natural products. Cell. Mol. life Sd., 54, 167-170. 

Fused tetracyclic and pentacyclic alkaloids constitute a relatively new class of natural products isolated mostly from ascidians and sponges. Cytotoxic, antimicrobial and antiviral activities have been reported for many of these compounds. The manzamine alkaloids, Fig. (33) are characterized by a complex pentacyclic diamine linked to C-l of P-carboline moiety. Manzamine have been isolated mainly from six different genera of marine sponges Haliclona, Pellina, Xestospongia, Ircinia, Pachypellin and Amphimedon. 

Cyclosporin (Section 16.1.3) is an undecapeptide that acts as a potent immunosuppressant. Seven of its eleven residues are N-methylated. Its synthesis in solution was carried out by a series of segment condensations)32,33 The didemnins (Section 16.1.4) are isolated from marine organisms known as tunicates. Their therapeutic potential lies in applications as antitumor, antiviral, and immunosuppressant agents. The didemnin family of natural products contains peptidomimetic residues including A,0-dimethyltyrosine-proline and leucine—2-(hydroxyisovaleryl)propionic acid and (4-hydroxy)-2,5-dimethyl-3-oxo-... 

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