Isolation and structure of constanolactones A and B, new cyclopropyl hydroxy-eicosanoids from the temperate red alga constantinea simplex
✍ Scribed by Dale G. Nagle; William H. Gerwick
- Publisher
- Elsevier Science
- Year
- 1990
- Tongue
- French
- Weight
- 315 KB
- Volume
- 31
- Category
- Article
- ISSN
- 0040-4039
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✦ Synopsis
Two new cyclopropyl and lactone containing eicosanoids, constanolactone A and 8, were isolated as synthetic diacetate derivatives from the temperate red alga Constantinea simp7ex and their structures determined by spectroscopic means. A hydrolysis product of one of these helped to define the lactone size in these new eicosanoids. The co-occurrence of three known 12-lipoxygenase metabolites, I2-S-HETE, 12-S-HEPE, and 12-oxododeca-5(Z), 8(E), 10(E)-trienoic acid, supports a 12-lipoxygenase origin for the new compounds. The metabolism of arachidonic acid (AA) by marine organisms is unique in that lipoxygenase pathways are widely used to produce a diversity of novel products, including oxidized AA derivatives from red algae"' and carbocyclized AA derivatives from marine corals and algae.%" Examination of the mechanistic details of prostaglandin biosynthesis in one coral Plexaura homomalla," has been shown to involve the intermediacy a novel 8-lipoxygenase , product, allene oxide 1.12 Further, both boiled and unboiled acetone powders from P. homomalla catalyze the carbocyclization of allene oxide 1 to cyclopentyl (2) and cyclopropyl (3) containing products.13 The significance of the production of cyclopropanoid 3 to normal physiological pathways of arachidonic acid metabolism in the coral is uncertain given that it is a very minor product of these incubation experiments and apparently not an enzymatic product of 1." Hence, our isolation of similar cyclopropyl lactones, constanolactones A (4) and B (5), as major natural products (3-4% of the extractable lipids) from the temperate red alga Constantinea simplex, suggests that such products are of physiological relevance, at least in marine plants.14 As part of an extensive survey of the biomedicinal potential of seaweed extracts from the Pacific Northwest of the United States, the crude lipid extract (CH,CldHeOH 2:l) of C. simplex (Seal Rock, Oregon) was found by TLC to contain a diversity of likely eicosanoidtype natural products giving colorful (blue, yellow, red) Cu(OAc), or H2S04 staining reactions. Vacuum chromatography of a June collection (2.0 g oil/620 g dry wt. of alga) yielded fractions that were mixtures of related substances. Following derivatization (CH,N,) and NP-HPLC (5% EtOAc/hex) of one chromatographic fraction, minor amounts of three known eicosanoids, IL-(S)-HETE (9 -2.0 mg, 0.1X), 12-(S)-HEPE (10 -0.3 mg, 0.015%) and 12-0x0-5(Z), 8(E), 10(E) dodecatrienoic acid (11 -0.9 mg, 0.044%), were all isolated as synthetic methyl ester derivatives (12-14). Another vacuum chromatography fraction (146 mg, 80% EtOAc/hex) was treated with Ac,O/pyr followed by CH,NdEt,O and NP-HPLC (35% EtOAc/hex) to yield three closely related and new compounds (6 -32.7 IQ, 1.6%; 7 -39.9 mg, 2.0%; 8 -2.3 mg, 0.11X), the structure elucidation and bi%synthetic significance of which are presented. Constanolactone A diacetate (6), [a]i3= -5.4' (c -3.05, CHCl,), was a colorless oil which gave a prominent (M + H -2HCMc)+ by HR CIMS (CH,) at 301.2165 (0.3 mamu dev.) analyzing for Caaii,02. The diacetate character of this derivative was readily apparent from NMR and