Guanidines polycyclic

Marine sponges are a source of an array of polycyclic diamine alkaloids of common biogenetic origin. This class of secondary metabolites has been the subject of four previous reviews [4-7]. Therefore, the present review will include literature reports previously not discussed, dealing with the isolation, structure determination, biological activities, and total synthesis of polycycUc diamine alkaloids isolated from marine sponges. This review will not include guanidine alkaloids [8,9] or the manzamine alkaloids [10,11], since these compounds have been recently reviewed elsewhere. Only polycycUc... 

A double tethered Biginelli reaction was carried out on the simple five-membered urea aldehyde 305 that reacted with the aliphatic and aromatic bis-ketoesters 306 and 307 giving compounds 308 and 309, respectively, in good yield, albeit with a diasteromeric ratio of 1 3. A series of different polycyclic bis-guanidines resembling betzelladine alkaloids were prepared <2003OL4485>. 

The reactions of thiourea and guanidine with cycloalkanones are carried out in the same manner [101]. But it is worthwhile noting that muticomponent reactions of urea-like compounds with ketones, containing an activated methyl or methyle-negroup, often do not stop after the formation of a pyrimidine ring. In fact numerous derived condensation processes can lead to more complicated polycyclic compounds, which are especially typical for the reaction of cycloalkanones [101]. 

Cyclocondensation routes also provide access to pyrimidines. 2,3-Disubstituted pyrido[2,3-/i]-quinazolin-4(3//)-ones are obtained via cyclocondensation of 5-aminoquinoline-6-caiboxylic acid with acid chlorides <02SC235>. 5,6,8-Trialkyl-7-methoxy-2-aminoquinazolines are obtained from 1,3-dimethoxybenzenes via cyclocondensation of intermediate dihydrobenzenes with guanidine carbonate <02TL3295>. Diastereoselective intramolecular hetero Diels-Alder cyclization of a pyrazole carboxaldehyde condensed onto 1,3-dimethylbarbituric acid (101) gave polycyclic heterocycle 102 <02T531>. An efficient one-step synthesis of cyclobutene-annelated pyrimidinones 103 from methyl 2-chloro-2-cyclopropylideneacetate and amidines has been... 

Finally, two polycyclic systems were built. First, the cyclic guanidine embedded into the 2-aminobenzimidazole nucleus 9.20a-f was used to buM the tricyclic library L9 (7680 members. Fig. 9.13) then a complex spiro-piolyheterocycle library LIO... 

Ptilomycalin A (96) is a novel polycyclic guanidine alkaloid isolated from the sponge Ptilocaulis spiculifer (31). It is highly cytotoxic, antifungal, and antiviral. The related alkaloids were reported from the Mediterranean sponge Crambe crambe that also contains other types of guanidine alkaloids such as... 

Two new polycyclic guanidine alkaloids, cambrescidins 826 and dehydroaranobine A, were isolated from the marine sponge Monanchora spp. [61]. The pentacyclic guanidine alkaloids inhibit HIV-1 envelope-... 

Polycyclic compound 478, which forms stable complexes with urea, guanidine, amidines and their derivatives, is covered by patents (1991USP15030728, 1994USP5283333). These complexes were used in a biological investigation. Receptor betaine molecule 479 was constructed for diagnostic tests for blood (serum) creatinine and renal insufficiency. 

Berlinck R. G. S., Braekman, J. C., Daloze, D., Bruno, I., Riccio, R., Ferri, S., Spampinato, S., and Speroni, E. (1993) Polycyclic guanidine alkaloids from the marine sponge Crambe crambe and Ca channel blocker activity of crambescidin 816. J Nat. Prod. 56, 1007-1015. 

The polycyclic systems with spiro rings such as 10 have been nominated as modified guanidines [23,24]. Murphy et al. [24a,24c] prepared tetracyclic guanidines (Murphy s guanidines) 10 by double sequential intramolecular cyclizations, as shown in Scheme 4.7. 

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]. 

Kashman, Y, Hirsh, S., McConnell, O.J. et al. (1989) Ptilomycalin A a novel polycyclic guanidine alkaloid of marine origin. Journal of the American Chemical Society, 111, 8925-8926. 

Bensemhoun, J., Bombarda, I., Aknin, M. et al. (2007) Ptilomycalin D, a polycyclic guanidine alkaloid from the marine sponge Monanchora dianchora. Journal of Natural Products, 70, 2033-2035. 

Chang, L., Whittaker, N. F., and Bewley, C. A. (2003). Crambesddin 826 and dehydrocram-bine A new polycyclic guanidine alkaloids from the marine sponge Monanchora sp. that inhibit HIV-1 fusion. / Nat Prod 66,1490-1494. 

Jares-Erijman, E. A., Ingrum, A. L., Carney, J. R., Rinehart, K. L., Sakai, R., (1993). Polycyclic guanidine-containing compounds from the Mediterranean sponge Crambe crambe. the structure of 13,14,15-isocrambescidin 800 and the absolute stereochemistry of the pentacyclic guanidine moieties of the crambeseidins. J. Org. Chem.5%, 4805-4808. 

A novel polycyclic guanidine alkaloid, ptilomycalin A (51), was isolated from a red sponge, Hemimycale sp., from the Red Sea (Kashman et al. 1989). The authors report using long-range connectivity information gleaned from both COLOC and HMBC spectra in the elucidation of the structure. Some of the correlations observed in the HMBC spectrum were reported in the paper and are shown on the structure. 

An analogous reaction sequence can be used to generate benzimidazoles and aminobenzimidazoles, involving the palladium-catalyzed intramolecular cyclization of aryl bromide-substituted amidines and guanidines, respectively (e.g.. Scheme 6.37) [48]. With aryl bromides, simple Pd(PPh3)4 or Pd2dba3/PPh3 catalysts are sufficient to mediate cyclization. This same approach is equally applicable to indazoles and polycyclic benzimidazoles [49]. 

Braekman, J.C., Daloze, D., Tavares, R., Hajdu, E., and Van Soest, R.W. M. (2000) Novel polycyclic guanidine alkaloids from two marine sponges of the genus Monanchora. J. Nat. Prod., 63,193-196. 

Guzii, A.G., Makarieva, T.N., Denisenko, V.A., Dmitrenok, P.S., Kuzmich, A.S., Dyshlovoy, S.A., Krasokhin, V.B., and Stonik, V.A. (2010) Monanchocidin A new apoptosis-inducing polycyclic guanidine alkaloid from the marine sponge Morumchora pulchra. Org. Lett., 12, 4292-4295. 

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