Sesterterpenic acids

ABSTRACT Marine invertebrates such as ascidians, sponges and others are a prolific source of bioactive secondary metabolites. We have isolated a variety of marine natural products from the Okinawan marine invertebrates by using the sea urchin egg assay. Our recent work, the isolation, structure determination and activities of chlorinated macrolides, sesterterpenic acids, a bromotyrosine derivative, acetogenin derived endoperoxides, diterpene alkaloids, sesquiterpene quinones and spiro-sesquiterpenes, is presented in this article. The syntheses of these metabolites are also described. 

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). 

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. 

Dysideapalaunic acid (16), which is closely related to kohamaic acids and inhibits an aldose reductase, was isolated from the marine sponge Dysidea sp. from the Palauan Sea by Nakagawa and co-workers in 1986 [22]. The Okinawan kohamaic acids have a different stereochemistry at CIS from 16 and previously isolated sesterterpenes, which are... 

Two new metabolites, 2-hexylidene-3-methylsuccinic acid 4-methyl ester 308 and an ophiobolane sesterterpene named halorosellinic acid 309, were... 

Aspergillus stellatus. This supports its biosynthesis via cyclisation of geranyl-farnesyl pyrophosphate followed by rearrangement as shown in Scheme 3 [10]. Surprisingly, the folding pattern must be different from that involved in the biosynthesis of stellatic acid (4), a previously isolated sesterterpene metabolite of A. stellatus [11]. 

A new class of sesterterpenes in which the middle three units of a penta-isoprenoid chain cyclised into a bicyclic system, leaving the first and the last isoprenoids to substitute the decaline moiety, was isolated from sponges of genus Dysidea and Ircinia. From the Palauan Dysidea sp. was isolated dysideapalaunic acid (107) that inhibited the aldose reductase [124]. An inhibitor of aldose reductase is expected to prevent neuropathy or cataract as a complication of diabetes. These diseases are caused by the accumulation of sorbitol in the peripheral nerve or the crystalline lens, as a result of enzymatic reduction of glucose by the aldose reductase in the sorbitol cycle [125,126]. The absolute stereochemistry of dysideapalaunic acid was established by its total synthesis [127,128],... 

Halorsellinic acid (66) [Fig. (26)] is an ophiobolane sesterterpene isolated from the marine fungus Halorsellinia oceanica that showed in vitro antimalarial activity with IC50 = 13 pg/mL [85]. 

The parent hydrocarbon skeletons of bieyelie sesterterpenes are derived predominantly from some sesquiterpenes. Diprenyldrimanes, for example, realized as (- -)-dysideapalaunic acid and related laetones, partly reported to be natural inhibitors of protein phosphatase, are isolated from the Caribbean sponge Dysidea etheria and other Dysidea species. Prenyldrimanes in higher plants are represented by (-)-salvisyriacolide from Salvia syriaca and as (-l-)-salvileucolide methylester from Salvia hypoleuca (Labiatae). 

Kaneda M, Takahashi R, litaka Y, Shibata S (1972) Retigeranic acid, a novel sesterterpene isolated from the lichens of Lobaria retigera group. Tetrahedron Lett 4609-4611... 

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