Marine metabolites, synthesis

Howard, B. M., Nonomura, A. M. and Fenical, W. 1980. Chemotaxonomy in marine algae secondary metabolite synthesis by Laurencia in unialgal culture. Biochem. Syst. Ecol. 8 329-336. 

Tricyclic systems found as a number of marine metabolites have attracted attention in recent years. The dihydropyrrolopyrazinone 165 was synthesized by Austin and co-workers as part of the synthesis of ( )-dibromo-phakellstatin by reaction of 163 with trichloroacetylpyrrole 164 (Equation 40) <20040L3881>. 

Anionic oxy-Cope rearrangement was also employed for the enantioselective total synthesis of compounds related to marine metabolites (equation 230)305 307, as well as for the preparation of diterpenoide vinigrol (equation 231)308 and cerorubenic acid-in... 

Wipf, P. Yoshikazu, U. (2000A) Total synthesis and revision of stereochemistry of the marine metabolite trunkamide A. J. Org. Chem., 65, 1037-49. 

This reaction has been used as the key step in the synthesis of some important bioactive marine metabolites by treatment of readily available 2-vinyltetrahydrofurans with dichloroketene (equation 199)713. 

Boehlow TR, Harbum JJ, Spilling CD (2001) Approaches to the Synthesis of Some Tyrosine-Derived Marine Sponge Metabolites Synthesis of Verongamine and Purealidin N. J Org Chem 66 3111... 

A key step in the total synthesis of the marine metabolite (—)-solanopyrone D (161) is the enantioselective organocatalytic intramolecular Diels-Alder reaction of the trienal (158) to the decalin aldehyde (160) in the presence of the imidazolidinone catalyst (159) (Scheme 45).187 Protonated 1,2-diamino-1,2-diphenylethane has been... 

Many of the studies reviewed in this chapter have focused on the meroplankton. However, little is known about ontogenetic shifts in concentrations and patterns of defense in marine invertebrate larval forms.40 Further work is needed to determine if, for a wider range of species, developing larvae are capable of secondary metabolite synthesis or if defensive compounds are derived directly from adults. While a number of studies have been conducted on chemical defenses in lecithotrophic larvae of benthic invertebrates, the database is still quite small for planktotrophic larvae. Additional carefully controlled studies of aposematism in marine invertebrate larvae are also needed to determine if there is indeed a general pattern of chemical defenses in conspicuously colored larvae. 

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],... 

In particular. Section I describes the structures and biological activities of selected classes of alkaloids. Almost half of the chapters focus their attention on terrestrial alkaloids (Chapters 1-5). The other half (Chapters 7-11) describe recent results in the field of marine alkaloids, whUe Chapter 6 is focused on neurotoxic alkaloids produced by cyanobacteria, microorganisms living in both marine and terrestrial environments. The particular emphasis on marine alkaloids undoubtedly reflects our long-standing research activity on marine metabolites, but it is also a result of the impressive amount of work carried out in the last few decades on marine natural product chemistry. Section II (Chapters 12-15) gives an account of modern techniques used for the detection and structural elucidation of alkaloids, while Section III is divided into two parts different methodologies for the synthesis of alkaloids and accounts of modem biosynthetic studies. 

A highly efficient synthesis of the marine metabolite laurencin (3.12) involves asymmetric glycolate alkylation (Scheme 3.5). 

The marine metabolite stypoldione (36) has attracted the attention of chemists owing to both its pharmacological properties and its challenging chemical structure. Xing and Demuth have recently reported an elegant synthesis of 36 via the tricyclic intermediate 35 [126,127]. In our laboratory... 

Dehydrothyrsiferol (3), an analogue of thyrsiferol (1), was the next marine metabolite discovered from Laurencia. In an effort to assess halogen-based secondary metabolite synthesis, Norte and co-workers isolated compound 3 in 1984 as a white crystalline solid [6]. This natural product was found in Laurencia pinnatifida located on the Cannary Islands of Spain. Its chemical structure was verified via chemical transformation into thyrsiferol (1). 

In the laboratory of Y. Takemoto, the asymmetric total synthesis of the marine metabolite, halicholactone was accomplished. One advanced intermediate contained a 1,2-vicinal diol moiety which was cleaved under mild conditions to afford the corresponding aldehyde. The Criegee oxidation was chosen to effect this transformation at low temperature, followed by the stereoselective allylation of the resulting aldehyde with tetraallyltin. 

A general synthetic route toward the marine metabolite eunicellin diterpenes was developed by G.A. Molander and co-workers.The power of this method was demonstrated by the completion of the asymmetric total synthesis of deacetoxyalcyonin acetate. A tricyclic (3-keto ester intermediate was methylated in the y-position with complete diastereoselectivity using dianion chemistry and the crude product was subjected to the Krapcho decarboxylation. This was one of the rare cases when the transformation did not only remove the methoxycarbonyl group, but at the same time epimerized the newly formed stereocenter to yield a separable mixture of methyl ketones. 

The secondary marine metabolite (+)-acetoxycrenulide has unprecedented structural features which prompted L.A. Paquette et al. to embark on its total synthesis. The eight-membered carbocycle of the target was constructed via a Claisen rearrangement. The bicyclic p,y-unsaturated lactone was subjected to Simmons-Smith conditions, that delivered the cyclopropyl ring exclusively from the p-face of the molecule as a result of the predominant ground-state conformation. 

Metallic lanthanum effects the stereoselective reductive dimerisation of 3-iodoflavanones to 3,3 -biflavanones as exemplified by the first synthesis of cf/-chamaejasmine <05OL271> and a Pd-catalysed diastereoselective cyclisation features in a route to the marine metabolite (-)-15-oxopuupehenol <05OL1477>. 

The many recent publications affirm the importance of this reaction in modem synthesis. Tanaka and Takemoto s synthesis of the marine metabolite halicholactone uses a sulfoxide route to the allylic alcohol 115. Notice the suprafacial [2,3]-sigmatropic rearrangement and that the OH group ends up in the middle of the diene. Attempted cyclopropanation of 115 gave a poor yield of a mixture of products.21... 

Synthesis and biological activity of the marine metabolite cylindrospermopsin 01CSR303. 

Since marine natural products generally occur as a family of closely related structures it is likely that, at least in certain cases, the biosynthetic enzymes are relatively nonspecific. This may only be true for a limited number of cases, however, this result does suggest potential payoffs for the chemoenzymatic synthesis of both known and novel analogues of marine metabolites. 

Nature has found it possible to assemble a wide range of furanosesqui- and diterpenes. Although it is quite clear that these substances are not biosynthesized via any sigmatropic scheme, the atom economy of such isomerization reactions appeared to us to warrant application to this field. A thrust in this direction would require, however, that a furan ring be willing to utilize its n electrons in a manner suitable to rebonding. Precedent for an adaptation of this type was scarce [41]. Nonetheless, we have succeeded in developing a relatively concise enantioselective synthesis of natural (+)-pallescensin A (81), a marine metabolite first isolated in 1975 [42] and prepared earlier on several occasions [43-48]. 

Swinholide A is an interesting physiologically highly active marine metabolite with a macrocyclic diolide structure and a polyketide carbon skeleton. Recently the first total synthesis of 161 was reported by I. Paterson et al. (21). We focused on the synthesis of the tetrahydropyran part of the molecule as represented by compound 162. The particular feature of this ring is that it bears the largest substituent (at C-27) in an axial arrangement, as shown by the X-ray crystal structure of 161. 

In a rather lengthy synthesis of the marine metabolite capnellene(12), Stille and Grubbs have highlighted the interesting... 

Complex phosphonates and phosphonium ylides have been used in a variety of syntheses. For example an olefination reaction of the phosphonate (244) has been used to construct the carbon skeleton in a convergent synthesis of the structural fragment (245) of the marine metabolite halichondramide 27 and Wittig reactions with the ylide (246) have been used to prepare the polycyclic cervinomycin A -trimethyl ether and A2-methyl ether. 2 Both complex phosphonates (247) and phosphonium ylides (248) have been investigated for use in the synthesis of calyculin A. Use of the phosphonate (247) was not successful due to a competing elimination reaction and the ylide (248) was used in the actual synthesis. 29... 

The marine metabolite diazonamide A (47) (Fig. 3) was isolated from the colonial ascidian Diazona angulata, collected from the ceiUngs of caves along the northwest coast of Siquijor Island in the Phihppines [31]. The original structure of diazonamide A was suggested by an X-ray crystallographic study of the p-bromobenzoyl derivative of diazonamide B (48) (Fig. 3). Harran and coworkers completed the synthesis of the proposed diazonamide A [32], which differs from the natural diazonamide A, and thus the revised structure is 47 [33]. 

The investigation outlined above resulted in a total synthesis of the anticancer marine metabolite DDM 1 in 1.6% overall yield for 21 linear steps. ° "... 

The structure and absolute configuration of the marine metabolite leptosphaerin (15) were confirmed by synthesis from... 

---