Sesterterpenes

Four related furanoid sesterterpenes have been isolated from sponges of the genus Ircinia. Ircinin-1 (94) and ircinin-2 (95) from Ircinia oros were found to be isomeric difurano-sesterterpenes containing an unusual conjugated tetronic acid moiety 60). Fasciculatin (96) from Ircinia fasci-culata 37) and variabilin (97) from /. variabilis 84) were shown to be closely related monofurano-sesterterpenes. 

Two more isomeric linear monofurano-sesterterpenes, furospongin-3 (98) and furospongin-4 (99), have been isolated in small yield from Spongia officinalis 49). 

Chart 9 lists the structures of the sponge furanoid sesterterpenes. 

Ircinin-1 (94) and -2 (95) proved to be resistant to all attempts at separation and work on their constitution was carried out on the mixture of the two isomers 60). The presence of two furan rings linked to each other by a methylene group was indicated by n.m.r. spectroscopy (five broad 1 H 

Chart 10. Reaction with alkali of conjugated tetronic acid ring 

Diterpenes Derived from Monocyclic Precursors Cembrene Taxanes 

Cocarcinogenic Diterpenes from the Euphorbiaceae and Thymelaeaceae Bicyclic Diterpenes Manool Derivatives Labdane Derivatives Clerodane Derivatives Tricyclic Diterpenes 

Diterpenes related to e r-kaurene (5p,10a-configuration). Other Structural Types Derived from the enr-Kaurane Skeleton Gibberellins Grayanotoxins 

Diterpenes in Chemosystematic Studies Biological Activity Phytoalexins Phytotoxins 

Antifeedant Compounds Insecticidal and Nematicidal Activity Diterpenes with Juvenile Hormone Activity Diterpenes That Prevent Reproduction in Insects Trail-Marking Pheromones Diterpenes from Marine Plants Sweeteners Medicinal Properties Antitumor Compounds Sesterterpenes Biosynthesis Biological Activity References 

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The seminal publication [ 12] on the isolation of retigeranic acid proposed a possible biosynthetic pathway by means of cyclization from geranyl famesyl pyrophosphate (12) (Fig. 10.2) to tertiary carbocationic cyclopentane 13. A series of [1, 5] and [1, 2] hydride shifts were proposed to establish the skeletal core of the sesterterpene, whose subsequent oxidation would yield retigeranic acid. 

Trauner and coworkers released a report on a unified approach to isopropyl containing frans-hydrindane sesterterpenes via a common intermediate [38]. Their effort provided compounds that lend themselves to the substitution patterns embedded in retigeranic acids A (1) and B (2) as well as oxygenated precursors providing access to other sesterterpenes such as nitidasin (6), astellatol (3), and YW3699 (89). 

Scheme 10.6 Trauner s synthesis of hydrindanone intermediates for sesterterpenes...

The [4+ 4]-cycloaddition reaction of tethered bis-dienes has been used by Wender and co-workers in total synthesis as exemplified in syntheses of ( )-salsolene oxide and (-l-)-asteriscanolide (Scheme 28). In the synthesis of ( )-salsolene oxide, a nickel(0)-catalyst cleanly effects the cycloaddition of the two conjugated dienes in compound 93 to afford the bicyclo[5.3.1]undecadiene in a good yield and with moderate selectivity.99 The first synthesis of (-l-)-asteriscanolide was accomplished in only 13 steps. The key [4+ 4]-cycloaddition reaction efficiently set the requisite eight-membered ring of (-l-)-asteriscanolide in good yield and with excellent diastereoselectivity.100 The diastereoselective [4 + 4]-cycloaddition has also been applied to the synthesis of the core ring system found in several sesterterpenes such as the ophiobolins (Scheme 28).101... 

Sesquiterpenes, sesterterpenes, dlbromotyrosine derivatives, isonitriles, isothiocyanates, polyalkylated indoles, macrolides, quinones, ancepsenolides, sterols... 

In European Reticulitermes termites however, 16 known terpene compounds were isolated from the soldier frontal gland secretion, including monoterpenes, sesquiterpenes, diterpenes, and one sesterterpene [184]. 

Kirsch G Koeng GM, Wright AD, Kamisnky RA. (2000) New bioactive sesterterpene and antiplasmodial alkaloids from marine sponge Hyrtios. JNat Prod 63 825-829. 

Overall, however, the immensity of temperate land corresponds to a most various secondary metabolic production, different from that of tropical land. The most renowned alkaloids belong to the morphine class (Chart 6.2.A1), and, in combination with isoprenoids, to the ergot and triterpene classes (Chart 6.2. A2). Prominent in the peptides are the cyclosporins (the first of which was isolated from a fiingus collected in Norway), streptogramins, and P-lactams (Chart 6.2.P). The isoprenoids are represented by pyrethrin monoterpenes, cedrane sesquiterpenes, ginkgolide and taxane diterpenes, ophiobolane sesterterpenes, and arborane and amyrin-like triterpenes (Chart 6.2.1). In the polyketides, epothilones, recently discovered from Myxobacteria, and the long known rapamycin, are two prominent classes of macrolides (Chart 6.2.FA/PO/C). 

Chart 7.2.11 Mono-, sesqui-, di-, and sesterterpenes (skeletons) from the Indo-Pacific (Smax=36, av=22 5 /fftnax=0.63, av=0.38)... 

Chart 8.3.12 Sesterterpenes, triterpenes, steroids, tetraterpenes, and polyprenyls (skeletons) typical of both marine and land organisms (for S and HseeC 8.3.11). 

Corey, E.J. Luo, G. Lin, L.S. (1997A) A simple enantioselective synthesis of the biologically active tetracyclic marine sesterterpene scalarenedial. J. Am. Chem. Soc., 119,9927-8. 

Rudi, A. Yosief, T. Schl er, M. Kashman, Y. (1999A) Bilosespenes A and B two novel cytotoxic sesterterpenes from the marine sponge Dysidea cinerea. Org. Lett., 1,471-2. 

Wright, A.E. McCarthy, P.J. Schulte, G.K. (1989) Sulfircin a new sesterterpene sulfate from a deep-water sponge of the genus Ircinia. J. Org. Chem., 54, 3472-4. 

A Californian sponge of the Halichondriidae family contained a sulfated sesterterpene hydroquinone and five sulfated sesterterpenes. The structures of the halisulfates 1-5 (359-363) were determined by interpretation of spectral data and a structure was proposed for halisulfate 6 (364). The halisulfates are antimicrobial and antiinflammatory [318]. The absolute configuration of halisulfate 3 (361), which was also isolated from Ircinia sp. from the Philippines, has been determined by application of the chiral amide method and by chemical degradation techniques [319]. Halisulfate 7 (365) is a sesterterpene sulfate from a Coscinoderma sp. from Yap, Micronesia [320]. 

Bioassay directed isolation of serine protease inhibitors from Coscinoderma mathewsi yielded the 1-methylherbipoline salts (366-367) of known sesterterpenes halisulfate-1 (359) and suvanine (358) [321]. Coscinosulfate 1 (368), a sesquiterpene sulfate, was isolated from a New Caledonian collection of C. mathewsi. It displayed significant activity as an inhibitor of the protein phosphatase Cdc25 [322]. A total synthesis starting from (+)-sclareolide was described [323]. 

Sulfircin (369), an antifungal sesterterpene sulfate was isolated as the iV,iV-dimethylguanidinium salt from a deepwater Ircinia species and its structure was determined by X-ray analysis [324]. Two sesterterpene sulfates, hipposulfates A (370) and B (371), were isolated from Hippospongia cf. metachromia from Okinawa and their structures were elucidated by interpretation of spectroscopic data. Both compounds possess an enolsulfate functionality [325]. 

The sesterterpene pyridinium alkaloid spongidine D (497) was isolated from a Spongia sp. from Vanuatu as an antiinflammatory agent [422]. 

A novel entry to decahydrocyclopentacyclooctene derivatives via the intramolecular photocycloaddition of fused a,/3-unsaturated y-lactones has been developed (80CC1011). Irradiation of the butenolide (153) in acetone solution gave both the fused and bridged photoadducts (154) and (155) (2-3 1). The major adduct was hydrolyzed, oxidized and esterified to afford (156). Reductive cleavage of the unsaturated keto ester (156) with lithium in ammonia afforded a five-component mixture of a,/3- and /3,y-unsaturated esters. Equilibration with 0.1M sodium methoxide in methanol converted the mixture into a single a,j8-unsaturated ester (157 Scheme 34). This annelative two-carbon ring expansion method may find application in the synthesis of ophiobolin and ceroplastol sesterterpenes. 

These types of compounds also showed other interesting properties, such as antineoplasic and cytotoxic activity reported from scalarane-type sesterterpenes of the Indian Ocean sponge Hyrtios erecta [109,110], and antituberculosis properties [111]. 

Several other marine sponges have been investigated in the last decade, in the search for novel bioactive sesterterpene molecules. A sample of the sponge Dysidea herbacea from the Red Sea is unique in that it contains cytotoxic sesterterpenes with a scalarin skeleton, e.g., scalardysin, Fig. (16) and the C2i-fiiranoterpene fiirospongolide, Fig. (17). 

This compound also showed antispasmodic activity [122], A variety of cytotoxic compounds was isolated, including a bishomosesterterpene and dysidiolide from another Dysideci sp., a sulfated sesterterpene hydroquinone from a Hippospongia sp., and two new sesterterpenes, lintenolides F and G from the Caribbean sponge Cacospongia linteiformis [123,124],... 

From the Maldives Black marine sponge Hyrtios erectci, several cytotoxic sesterterpenes were isolated, such as the penytacyclic sesterterpenes designated sesterstatins [125-127] and puupehenone, Fig. (18) with a quinone-methide system [128], Three novel cytotoxic nor-sesterterpenes, rhopaloic acid A, Fig. (19), B and C, were recently isolated from the sponge Rhopciloeides sp. 

Additionally, during the search for biologically active sponge metabolites belonging to the sesterterpenoid class, a sulfated sesterterpene hydroquinone, halisulphate, Fig. (20), was isolated from the dark brown sponge Halichotidriidae sp. 

These compounds are the first natural halogenated sesterterpenes. A subsequent study tentatively identified this fungus as Fusarium heterosporum... 

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