Clavulones, new type of prostanoids from the stolonifer quoy and gaimard

Kikuchi, Hiroyuki; Tsukitani, Yasumasa; Iguchi, Kazuo; Yamada, Yasuji

doi:10.1016/s0040-4039(00)85788-3

Cited by 123 publications

(71 citation statements)

References 8 publications

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“…Side-by-side incubations were performed at room temperature in 1 ml of 50 mM Tris pH 8.0 containing 500 mM NaCl, 2 mM CaCl 2 and 0.01% Emulphogene detergent using [ 14 Incubations were conducted in a 1 ml quartz cuvette and the rate of reaction monitored by repetitive scanning from 350-200 nm using a Lambda-35 spectrophotometer (Perkin-Elmer). Reactions were stopped by addition of 500 l MeOH and the solution placed on ice.…”

Section: Incubation With Enzymesmentioning

confidence: 99%

“…In side-by-side incubations monitored in the UV, it was apparent that the 20:3 6-derived 8 R -HPETrE disappeared more quickly than the corresponding arachidonic acid-derived 8 R -HPETE. These side-by-side reactions were also conducted using 14 Clabeled fatty acid substrate, and, after extraction of these samples using C18 cartridges, RP-HPLC analysis showed distinctly different profi les of products ( Fig. 3A ).…”

Section: Retention Of Hydroperoxy Oxygens In the Epoxyalcoholmentioning

confidence: 99%

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8R-Lipoxygenase-catalyzed synthesis of a prominent cis-epoxyalcohol from dihomo-γ-linolenic acid: a distinctive transformation compared with S-lipoxygenases

Jin

Boeglin

et al. 2012

Journal of Lipid Research

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This article is available online at http://www.jlr.org dins for research ( 3 ). Due to differences in the prostaglandin profi le from that typically seen in mammalian systems, for some time it was suspected that there existed a different prostaglandin biosynthetic pathway in coral ( 4,5 ). Although this putative noncyclooxygenase pathway of prostaglandin synthesis turned out to be a red herring and cyclooxygenase accounts for the biosynthesis ( 6, 7 ), research into polyunsaturated fatty acid metabolism in coral extracts uncovered other interesting biochemistry. Bundy and colleagues studied the related coral Pseudoplexaura porosa and uncovered 8 R -lipoxygenase activity, the fi rst known existence of an R -specifi c lipoxygenase ( 8 ). 8 R -LOX was subsequently found to be widespread in corals including in P. homomalla ( 5, 9 ) as well as in many marine invertebrates ( 10 ), and a 12 R -LOX is highly conserved and functionally essential in mammals ( 11,12 ). A second novel activity detected in coral extracts was allene oxide synthase ( 5, 13 ), which transforms the 8 R -LOX product, 8 R -hydroperoxy-eicosatetraenoic acid, to an allene epoxide ( 5 ), a proposed intermediate in biosynthesis of cyclopentenones such as the clavulones ( 14-16 ), and which hydrolyzes in vitro to an ␣ -ketol derivative ( 5 ).The work described in the present paper was initiated in the early 1990s, before the cloning of P. homomalla cyclooxygenases and lipoxygenases. It concerns an unexpected difference we observed in the metabolism of arachidonic acid (20:4 6) and dihomo-␥ -linolenic acid (20:3 6) in extracts of P. homomalla ; a prominent, relatively polar, product is formed specifi cally from 20:3 6. This difference had been noted before in work from the E. J. Corey laboratory ( 17 ).Abstract Conversion of fatty acid hydroperoxides to epoxyalcohols is a well known secondary reaction of lipoxygenases, described for S -specifi c lipoxygenases forming epoxyalcohols with a trans -epoxide confi guration. Here we report on R -specifi c lipoxygenase synthesis of a cis -epoxyalcohol. Although arachidonic and dihomo-␥ -linolenic acids are metabolized by extracts of the Caribbean coral Plexaura homomalla via 8 R -lipoxygenase and allene oxide synthase activities, 20:3 6 forms an additional prominent product, identifi ed using UV, GC-MS, and NMR in comparison to synthetic standards as 8 R ,9 S -cis -epoxy-10 S -erythro -hydroxy-eicosa-11 Z ,14 Zdienoic acid. Both oxygens of In the late 1960s and early 1970s, high concentrations of prostaglandin esters were identifi ed in the Caribbean sea whip coral Plexaura homomalla ( 1, 2 ), and for a few years this abundant octacoral served as a source of prostaglan-

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Section: Incubation With Enzymesmentioning

confidence: 99%

Section: Retention Of Hydroperoxy Oxygens In the Epoxyalcoholmentioning

confidence: 99%

8R-Lipoxygenase-catalyzed synthesis of a prominent cis-epoxyalcohol from dihomo-γ-linolenic acid: a distinctive transformation compared with S-lipoxygenases

Jin

Boeglin

et al. 2012

Journal of Lipid Research

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“…NaHCO 3 and NaS 2 O 3 .5H 2 O solution (10 mL) and extracted with CH 2 Cl 2 (2×20 mL). The combined extracts were dried (Na 2 SO 4 ), filtered and concentrated to give dialdehyde 11 (94 mg, 95%) as a yellow oil; 1 …”

Section: -(Tert-butyl-dimethyl-silanyloxy)methanol-910-dihydro-91mentioning

confidence: 99%

“…However, the cyclization process using β-allyl ester with an excess of LDA provided cyclopentenone in moderate yields together with the formation of the enaminone 10 . As an extension, we here report a novel building block for the synthesis of cyclopentenone prostaglandins, in the particular PGA 1 analog clavulones. The synthesis of this key compound, spirocyclopente-dione anthracene adduct, could be envisioned from the cyclopentenol readily obtained from the 1,6-diene using a ring-closing metathesis reaction.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Spirocyclopente-Dione Anthracene Adduct, Precursor of the Cyclopentenone Prostagladins Via Ring-Closing Metathesis Reaction

Eksinitkun¹,

Pyne²,

Phutdhawong³

2013

Chem Sci Trans

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A synthesis of the spirocyclopente-dione anthracene adduct, a precursor of the cyclopentenone prostaglandins has been reported. The synthesis involved a Diels-Alder reaction of anthracene and dimethyl fumarate to afford 3 followed by reduction, oxidation and esterification reactions to provide methyl ester anthracene adduct 8, which further converted to the the allylic alcohol (12). Then, Ring-Closing Metathesis (RCM) reaction afforded the cyclopentenol anthracene adduct, which after oxidation provided the spirocyclopente-dione anthracene adduct in good yields.

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“…Reagents and Conditions 2 , THF H 2 O, ii) NaBH 4 , MeOH KOH aq., (g) i) H 2 , Pd C, EtOH, ii) Dess-Martin periodinane, iii) vinyl magnesium bromide, iv) TBDMSCl, imidazole, (h) i) DIBAH, ii) Dess-Martin periodinane, iii) CH2＝C(CH3)CH2P(O)Ph2, n BuLi, HMPA, THF, -78°C to rt, iv) n Bu4NF), (i) DessMartin periodinane, (j) i) TsCH2NC, t BuOK, DME-t BuOH (5：1), 0°C to rt, ii) KHMDS, MeI, toluene, (k) i) DIBAH, ii) NaClO2, 2-methyl-2-butene, NaH 2 PO 4 , t BuOH H 2 O (4：1), iii) DPPA, Et 3 N, toluene, rt to 100°C, iv) DIBAH. 25) fuscol, 26,27) phomactin D 30) の全合成を行っている． …”

Section: Scheme 4 Reagents and Conditionsunclassified

Studies on Discovery and Synthesis of Bioactive Marine Organic Molecules

Yamada

2002

YAKUGAKU ZASSHI

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This paper describes the discovery and total synthesis of bioactive marine natural products conducted in our laboratory. Clavulone, chlorovulone, bromovulone, and iodovulone are antitumor marine prostanoids isolated from the Okinawan soft coral Clavularia viridis. The synthesis of clavulone and chlorovulone was achieved from chiral 4-hydroxy-2-cyclopentenone. Marine prostanoid punaglandins 3 and 4 were synthesized via similar methodology. The chemical structures of punaglandins 3 and 4 were revised by these syntheses. Dollaberane-type diterpenoid stolonidiol and claenone were isolated from Okinawan soft coral Clavularia sp. Stolonidiol showed potent choline acetyltransferase-inducible activity in cultured basal forebrain cells. The synthesis of stolondiol and claenone was conducted via sequential Michael reaction and retro-aldol reaction. Aragusterols, isolated from the Okinawan marine sponge Xestospongia sp., are structurally unique steroids possessing a rare 26,27-cyclo structure in the side chain. Aragusterols express potent in vivo antitumor activity against L1210 leukemia in mice. The synthesis of aragusterols was carried out via stereoselective construction of the side chain and stereocontrolled coupling reaction with the steroid skeleton. Kalihinane-type diterpenoid kalihinol A, isolated by Scheuer, has remarkable in vitro antimalarial activity. The absolute conˆguration of kalihinol A was determined by applying the CD exciton chiral method. Synthesis of kalihinene X, a kalihinane-type diterpenoid, was achieved. This synthesis involves the regioselective coupling reaction of carbanion of alkyl sulfone with epoxyalcohol and construction of cis-decalin by an intramolecular Diels-Alder reaction.

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Clavulones, new type of prostanoids from the stolonifer quoy and gaimard

Cited by 123 publications

References 8 publications

8R-Lipoxygenase-catalyzed synthesis of a prominent cis-epoxyalcohol from dihomo-γ-linolenic acid: a distinctive transformation compared with S-lipoxygenases

8R-Lipoxygenase-catalyzed synthesis of a prominent cis-epoxyalcohol from dihomo-γ-linolenic acid: a distinctive transformation compared with S-lipoxygenases

Synthesis of Spirocyclopente-Dione Anthracene Adduct, Precursor of the Cyclopentenone Prostagladins Via Ring-Closing Metathesis Reaction

Studies on Discovery and Synthesis of Bioactive Marine Organic Molecules

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