Ilimaquinone

Luibrand RT, Erdman TR, Vollmer JJ, Scheuer PJ, Finer J, Clardy J (1979) Ilimaquinone a sesquit-erpenoid quinone from a marine sponge (Hippospongia metachromia).Tetrahedron 35 609-612 Moore BS (2005) Biosynthesis of marine natural products microorganisms (Part A). Nat Prod Rep 22 580-593... 

Cell biology ilimaquinone ma-osesquiterp./inducing ccnnplete vesiculation of marine Hippospongia... 

Ilimaquinone (12) belongs to the same structural class and was isolated from Hippospon-gia metachromia.3i 36 It also showed modest antimalarial activity. Moloka iamine (13) is a... 

Puupehenone (63) is a member of a distinctive family of sponge metabolites — a sesquiterpene joined to a C6-shikimate moiety — first exemplified by the quinol-quinone pair of avarol and avarone. Among the varied activities that have been reported for this diverse class of compounds is the property of ilimaquinone to inhibit replication of the HIV virus.78 Preliminary screening of puupehenone against Mycobacterium tuberculosis showed 99% inhibition of the organism. A series of chemical modifications have been conducted on puupehenone to study the effect on its biological activity. 

As a synthetic application, stereoselective synthesis of potent anti-HIV (—)-ilimaquinone, is shown in eq. 8.21. 

Ilimaquinone (29) is a marine sesquiterpene quinone first isolated in 1979 from the sponge Hippospongia metachromia90 It has been reported to have mild antibacterial, antiviral, antifungal, and anti-inflammatory activities, but more interestingly, ilimaquinone has been found to break down the Golgi apparatus into small vesicles, thereby blocking cellular secretion.91 92... 

In a classic paper, Snapper synthesized an ilimaquinone-agarose-affinity resin (30), which was incubated with homogenized bovine liver and then washed extensively.93 Proteins retained by the resin were separated by gel electrophoresis, yielding six main protein bands. Amino acid sequencing of these bands revealed three proteins involved in the activated methyl cycle — SAHase, S-adenosylmethionine synthetase (SAM synthetase), and catechol-O-methyltransferase (COMT) — as well as three unrelated proteins. Subsequent enzymatic assays established that ilimaquinone is a competitive inhibitor of SAHase, but has little effect on the activity of SAM synthetase or COMT. The authors noted that a consequence of SAHase inhibition would be the intracellular accumulation of SAH, which is a potent feedback inhibitor of methyltransferases. These results support the assertion that methylation events play an important role in cellular secretory events and vesicle-mediated processes. The study also highlighted the problem of nonspecific interactions as only one of the six isolated proteins was shown to interact in any way with the natural product. 

Although smenorthoquinone was initially assigned an ortho quinone structure, both the spectroscopic data and results from chemical transformations are more consistent with the para quinone structure shown in this review. The principal evidence cited for an ortho rather than para quinone structure was the ability of smenorthoquinone to form an adduct 109 with ort/to-phenylenediamine. Ilimaquinone [75], which has been clearly established to be a /pa/ a-quinone, undergoes a similar reaction with o/t/io-phenylenediamine to yield the adduct 110. In both cases this is possible due to the tautomerization between ortho and para forms (see Figure 1). Most telling however is the spectroscopic data for smenorthoquinone, which is very similar indeed to that of ilimaquinone. Such a correlation would not be likely if smenorthoquinone was an ortho rather than para quinone as originally proposed. 

Dactylospongia elegans 2 6 mp 145-147°C l l546 -14° (CH2CI2) Biogenetic grounds (co-occurs with ilimaquinone)... 

Fasdospongia sp 4 7 Pale yellow solid, mp 108-109.5°C I ]S46 -31 (CHCI3) Chemical correlation to ilimaquinone... 

As reviewed in an earlier volume in this series (110) the absolute stereochemistry attributed to ilimaquinone [75] on the basis of circular dichroism measurements was incorrect. The correct absolute stereochemistry for ilimaquinone was ultimately established by degradative correlation to aureol [49]. The absolute stereochemistry of aureol had been determined via X-ray analysis of a monobromo derivative. This stereochemical reassignment to ilimaquinone was important for reasons other than simply establishing the correct stereostructure for this particular marine metabolite. Ilimaquinone is a common co-metabolite in sponges that in turn have been the source of a variety of new sesquiterpene/quinones. Frequently these new compounds have been attributed the same "absolute stereochemistry" as ilimaquinone [75], principally on the basis of biosynthetic considerations. 

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