Coralloidolide A and Coralloidolide B,the First Cembranoids from a Mediterranean Organism,the Alcyonacean Alcyonium coralloides

The alcyonacean Alcyonium ( = Parerythropodium) coralloides (PALLAS 1766) is the first Mediterranean organism shown to contain cembranoids. These are of unusual type like coralloidolide A ( = (?)-(1R*, 2R*, 3R*, 12S*, 5Z, 7Z, 9Z)-1, 2:7, 10-diepoxy-12-isopropenyl-5, 9-dimethylcyclotetradeca-5, 7, 9-triene-1, 3-carbolactone; (?)-6) and coralloidolide B ( =(?)-(1R*,2S*,3R*,7S*,10S*,12S*,5Z,8Z,)-2, 7:7, 10-diepoxy-1, 10-dihydroxy-12-isopropenyl-5, 9-dimethylcyclotetradeca-5,8-diene-1,3-carbolactone; (?)-8). Structural assignments are mainly based on 1D- and 2D-NMR data and on chemical transformations.     

Novel cembranolides (Coralloidolide D and E) and a 3,7-Cyclized cembranolide (Coralloidolide C) from the mediterranean coral Alcyonium coralloides

The Mediterranean alcyonacean Alcyonium (= Parerytkropodium) coralhides (PALLAS, 1766) is shown to contain three novel diterpenes which are of biogenetic significance: the 3,7-cyclized cembranoid Coralloidolide C ( = (+)-(6R*, 7R*, 11S*, 12aS* 3aE)-7,8-epoxy-3,5,6,7,8,9,10,11,12,12a-decahydro-12a-hydroxy-11-isopropenyl-1,4-dimethyl-3-oxocyciopentacydoundecene-8,6-carbolactone; (?)- 3 ), the O-bridged diketonic cembranolide Coralloidolide D (= (+)-(1R*, 2S*, 3R*, 5R*, 12S*, 8Z)-2,5-epoxy-1-hydroxy-12-isopropenyl-5,9-dimethyl-7,10-dioxocyclotetradeca-8-ene-1,3-carbolactone; (+)- 4 ), and the diketonic epoxycembranolide coralloidolide E (=(+)-(1R*, 2R*, 3R*, 12S*, 5Z, 8Z)-1,2-epoxy-12-isopropenyl-5,9-dimethyl-7,10-dioxocyclotetra-deca-5,8-diene-1,3-carbolactone; (+)- 5 ), The latter in pyridine at r. t. undergoes a double bond shift from C(4) = C(5) to C(4) = C(18) to give the isomer (?)- 7 . Structural assignments are mainly based on ID and 2D NMR and MS spectral data. Either corailoidolide A ((?)- 1 ) or the hypothetic unsaturated 1,4-diketone 9 can be envisaged as the precursors of all coralloidolides.     

Coralloidin C,D, and E: Novel Eudesmane Sesquiterpenoids from the Mediterranean Alcyonacean Alcyonium coralloides

The Mediterranean alcyonacean Alcyonium (=Parerythropodium) coralloides (Pallas, 1766) is shown to contain the novel eudesmane sesquiterpenoids coralloidin C (=(–)?(4R,10S)-eudesma-5,7(11)-dien-15-yl acetate; (–)? 4 ), coralloidin D (=(–)?(10R*)-eudesma-4,7(11)-diene-12,13-diyl diacetate; (–)? 7 ), and coralloidin E (=(+)?(4R*,10R*)-eudesma-5,7-dien-11-ol;(+)? 8 ). The absolute configuration of (–)? 4 is derived by the exciton-coupling method, applied to deacetylcoralloidin C_p-anisate ((–)? 6 ). Coralloidin E((+)? 8 ), being also obtained on treatment of deacetylcoralloidin A (=(+)?(4R*, 8R*, 10R*)-eudesma-5,7(11)-dien-8-ol; (+)? 2 ) with (COCl)₂ in DMSO, is configurationally correlated to coralloidin A (=(+)?(4R*, 8R*, 10R*)-eudesma-5,7(11)-dien-8-yl acetate; (+)? 1 ). Under acidic conditions, (+)? 2 undergoes a complex rearrangement giving (+)-(3R*, 4S*, 5R*, 6R*, 7S*)-arist-10-(1)-en -3-ol ((+)? 9 ), which is also obtained, together with (+)? 8 , on attempts to mesylate (+)? 2 .     

Isolation of a Bioactive Sterol from the Soft Coral Lobophytum Mirabile

A cytotoxic sterol, 24ξ-melhylcholestane-3β,5α,6β,25-tetrol 25-monoacetate (1) was isolated from the soft coral Lobophytum mirabile. This polar sterol showed moderate cytotoxicity toward P388 cells.     

Sarcoconvolutums F and G: Polyoxygenated Cembrane-Type Diterpenoids from Sarcophyton convolutum,a Red Sea Soft Coral

Natural products and chemical analogues are widely used in drug discovery, notably in cancer and infectious disease pharmacotherapy. Sarcophyton convolutum (Alcyoniidae) a Red Sea–derived soft coral has been shown to be a rich source of macrocyclic diterpenes and cyclized derivatives. Two previously undescribed polyoxygenated cembrane-type diterpenoids, sarcoconvolutums F (1) and G (2), as well as four identified analogues (3–6) together with a furan derivate (7) were isolated from a solvent extract. Compounds were identified by spectroscopic techniques, including NMR, HREIMS, and CD, together with close spectral comparisons of previously published data. Sarcoconvolutum F (1) contains a rare 1-peroxid-15-hydroxy-10-ene functionality. Isolated metabolites (1–7) were screened against lung adenocarcinoma (A549), cervical cancer (HeLa) and oral cavity carcinoma (HSC-2) lines. Compound 4 exhibited an IC₅₀ 56 µM and 55 µM against A549 and HSC-2 cells, respectively.     

软珊瑚Sarcophyton crassocaule中Cembrane型二萜的分离与鉴定

从采自中国南海西沙群岛海域的软珊瑚Sarcophytoncrassocaule中分离得到一种结构新颖的Cembrane型二萜,经¹HNMR,¹³CNMR,HMQC,¹H-¹HCOSY,NOESY,FABMS和X射线晶体衍射确定其结构,命名为SarcocrassolideB它对P388的细胞毒性为1.5μg/mL.     

On the First Marine Stigmastane Sterols and Sterones Having a 24,25-Double Bond. Isolation from the Sponge Stelletta sp. of Deep Coral Sea

The sponge Stelletta sp. (Astrophorida, Stellettidae), collected at ?700 m in the Coral Sea, is shown to contain sterones and sterols of the stigmastane type with a C(24)?C(25) bond for which there is no precedent in the sea. Structure elucidation of the second abundant of these steroids, stigmasta-4,24(25)-dien-3-one ((+)- 1 ), is based on 1D and 2D NMR spectra and chemical transformation to acetate (?)- 5 . Stigmasta-4,24(25)-diene-3,6-dione ((?)- 3 ), present in trace amounts in the sponge, was obtained in sufficient quantity for NMR study by oxidation of the also present, inseparable, and abundant 4:1 mixture of stigmasta-5,24(25)-dien-3β-ol ( 6 ) and its 5,6-dihydro derivative 7 (Scheme 1). This oxidation also afforded the ketone analogues (+)- 8 and (+)- 9 , which could be separated, thus making structure elucidation possible. The 6β-hydroxystigmasta-4,24(25)-dien-3-one ((+)- 4 ), also present in trace amounts in the sponge, was obtained in sufficient amount for NMR study, together with its C(6) epimer (+)- 11 , by hydroperoxidation of (+)- 8 followed by deoxygenation (Scheme 2). The last trace steroid of the sponge, stigmasta-4,6,24(25)-trien-3-one ((?)- 2 ), was structurally elucidated using limited NMR data and comparison with the other stigmastanes. These stigmastanes, as the only steroids of this sponge, are likely to function as stabilizers of its cell walls; their phytosteroid structure, for a sponge which lives in the dark of deep waters, suggest origin through a complex food chain, possibly followed by bioelaboration in the sponge.     

Isolation from the Mediterranean Stolonifern Coral Sarcodictyon roseum of Sarcodictyin C,D, E,and F,novel diterpenodic alcohols esterified by (E)- or (Z)-N(1)-methylurocanic acid. Failure of the carbon-skeleton type as a classification criterion

It is shown here that the stoloniferan coral Sarcodictyon roseum of east Pyrenean waters contains four novel diterpenoids, sarcodictyin C ((?) -3 ), D ((?) -4 ), E ((+)- 5 ), F ((+)- 6 ), which are related to sarcodictyin A ( = (?)-(4R,4aR,7R,10S,11S,12aR,1Z,5E,8Z-7,10-epoxy-3,4,4a,7,10,11,12,12a-octahydro-7-hydroxy-6-(methyoxycarbonyl)-1,10-dimethyl-4-(1-methylethyl)-benzocyclodecen-11-yl (E)-N¹-methylyrocanate; ((?)? 1 ), previously isolated from the same coral. Sarcodictyin C ((?) -3 ) and D ((?) -4 ) and the 3α-hydroxy and 3α-acetoxy derivatives of (?) -1 ), sarcodictyin E ((+) -5 ) is the (Z)-urocanate isomer of (?) -3 ), and sarcodictyin F ((+) -6 ) is the 1α-hydroxy-2-ene isomer of (?) -3 . In all cases, the nine-membered ring is locked, and the molecule stabilized, by the urocanic appendage; when this is removed in MeOH/KOH, the C(11)–O^? function is free to attack at C(5), and retro-condensations then lead to the ring-contracted butenolides 11 (from (?) -3 ) or 10 (from(?) -1 ) with extrusion of the hydroxyfuran nucleus (Scheme 3). Under the same conditions, with (?) -3 , the C(3)-O^? group competitively attacks at C(5), the hydroxyfuran nucleus is expelled, and aldehyde 14 is formed. Peculiarly, in the reaction of (?) -3 with MeOD/KOD, the ring-contracted butenolide 17 contains D at the 4′-ax position. The sarcodictyins are unique in these chemical properties, not shared by the cladiellanes which have the same C-skeleton.     

Sinularia属珊瑚中嘧啶类化合物的分离与鉴定

分离和鉴定了采自中国南海硇州岛软珊瑚Sinularia Bassica样本中新的嘧啶类化合物。样本用工业酒精提取,提取物溶液经乙酸乙酯萃取后,萃取物经硅胶柱层析,以极性不断增大的溶剂体系(石油醚-乙酸乙酯、氯仿-甲醇)梯度洗脱,再经过HPLC分离,得到2,4(1H,3H)-嘧啶二酮、5-甲基-2,4(1H,3H)-嘧啶二酮、1,3-二甲基-2,4(1H,3H)-嘧啶二酮和5-甲氧基-1,3-二甲基-2,4(1H,3H)-嘧啶二酮4种新的嘧啶类化合物,其结构通过红外光谱、1HNMR和13C NMR等光谱数据分析确定。     

Illudalane sesquiterpenoids from the soft coral Alcyonium paessleri: the first natural nitrate esters

Fifteen illudalane sesquiterpenoids, alcyopterosins A-O (1-15) have been isolated from the subAntarctic soft coral Alcyonium paessleri which was collected at a depth of 200 m near the South Georgia Islands, and their structures were elucidated by spectroscopic techniques. Eight of these compounds (2, 3, 5-8, 10, and 13) are the first natural nitrate esters, while the other four (1, 4, 11, and 12) are chlorinated. These compounds are as well the first illudalane sesquiterpenoids to be isolated from the marine environment. Compounds 1, 3, 5, and 8 showed mild cytotoxicity toward human tumor cell lines.     

Oceanapins A–F,Unique Branched Ceramides Isolated from the Haplosclerid Sponge Oceanapia cf. tenuis of the Coral Sea

A series of ceramides, called oceanapins A–F ( 2–7 ), which are unique for branching at both the sphingosine and fatty-acid chains, have been isolated as pure compounds from the haplosclerid sponge Oceanapia cf. tenuis of the Coral Sea. Following acid hydrolysis, both the fatty-acid and the sphingosine portions were obtained separately, which allowed their unequivocal structural definition. The absolute configuration was secured via protection of C(1′)–OH and Mosher's esterification at C(3′)–OH of the oceanapins.     

3Alpha,7alpha,12alpha-triacetoxy-5beta-cholanic acid, a steroid from the Formosan soft coral Alcyonium sp. (Alcyoniidae)

Chemical investigation of the organic extract of a soft coral belonging to the genus Alcyonium furnished a steroid, 3alpha,7alpha,12alpha-triacetoxy-5beta-cholanic acid (1). The structure of steroid 1 was assigned on the basis of spectroscopic evidence, particularly in 1D and 2D NMR experiments. The configuration of steroid 1 was further supported by molecular mechanics calculations.     

The First Example of Optically Active Chlorophosphine: T-Butylphenylphosphinochlorioite

Abstract

In general, alkylthiophosphonium salts can react with nucleophiles both in the sense of the Arbusov rearrangement (a) and the exchange of alkylthio groups at the P atom (b). We have recently demonstrated¹ that in the case of highly “thiophilic” nucleophiles such as mercaptide anions or tris(N, N-dimethylamine)phosphine the reactive centre is the sulphur atom (c).     

Isolation,Structural Analysis and Biological Activity Assays of Biselisabethoxanes A and B: Two Dissymmetric Bis-Diterpenes from the Southwestern Caribbean Sea Gorgonian Coral Pseudopterogorgia elisabethae

Two novel dissymmetric diterpenoids, biselisabethoxanes A and B (1 and 2), were isolated from the hexane extracts of the gorgonian coral Pseudopterogorgia elisabethae. Biselisabethoxane A (1) represents the first example of a marine-derived C₄₀ dimer made of two distinct diterpene fragments, whereas biselisabethoxane B (2) is a fused heterodimer stemming from coupling of two amphilectane-based fragments. The structures of 1 and 2 were elucidated based on 1D and 2D NMR spectral data analysis. The molecular structure of 1 was subsequently confirmed by X-ray crystallographic analysis. When evaluated for their inhibitory effects in a series of well-established biological activity assays the isolated compounds were shown to moderately inhibit the growth of Mycobacterium tuberculosis.     

First Example of Fluorinated Phenanthroline Diamides: Synthesis,Structural Study,and Complexation with Lanthanoids

An efficient approach to the synthesis of diamides of 4,7-difluoro-1,10-phenanthroline-2,9-dicarboxylic acid was elaborated. Direct nucleophilic substitution with 4,7-dichloro-1,10-phenanthroline precursors opened access to difluoro derivatives in high yield. As a result, four new fluorinated ligands were prepared in up to 88% yield. Their structure was proved by a combination of spectral methods and X-ray data. A set of lanthanoid complexes was prepared to demonstrate the utility of new ligands. The structure of the complexes was studied in solid state (IR-spectroscopy, X-ray diffraction) and in solution (NMR-spectroscopy).     

Adriadysiolide,the First Monoterpenoid Isolated from a Marine Sponge

Spectra and chemical transformations allow to establish the gross structure 6,7-epoxy-4,7-dimethyl-l-oxa-spiro[4.4]non-3-en-2-one for adriadysiolide ( 1 ), the first monoterpenoid isolated from a marine sponge, a Dysidea sp. of the Adriatic Sea. Its configuration 5R*, 6S*, 7S* as given in 1a is derived from diastereoselective total syntheses of both 1a and its diastereoisomer 1b via stereochemically predictable peracid epoxidations of olefinic precursors. Thus, OH assistance in allylic alcohol 8 leads to oxirane 13 which is subjected to methyl cuprate conjugate addition to give epiadriadysiolide ( 1b ), whilst electronic deactivation by a neighboring heterocyclic O-atom in intermediate 5 , derived from 8 mainly leads to adriadysiolide ( 1a ). Comparative ¹H-NMR shift-reagent effects with 1a and 1b , evaluated with the aid of molecular-mechanics calculations, support these conclusions.