Marine natural products: Cytotoxic spermidine derivatives from the soft coral sinularia brongersmai

Two new cytotoxic spermidine derivatives isolated from the Pacific soft coral $\text{Sinularia brongersmai}$ have been identified as CH₃(CH₂₈-C(CH₃)=CH-CO-NH(CH₂)₃-N(CH₃)- (CH₂)₄-N(CH₃)₂ and its dihydro analog by spectral methods combined with chemical conversions. Acid hydrolysis of the saturated amide followed by esterification yielded methyl 3-methyldodecanoate.     

Synthesis and structural revision of calafianin, a member of the spiroisoxazole family isolated from the marine sponge, Aplysina gerardogreeni

Calafianin 1 was successfully synthesized by employing a spiroisoxazoline compound, which was produced by electrochemical oxidation of the oximino-phenol derivative 7 followed by reduction. This investigation revealed a structural revision of 1, the trans-relationship of two oxygen atoms between the epoxide and the isoxazoline.     

Synthesis and absolute configuration of two diastereoisomeric (1R,2S,3R)-and (1S,2S,3R)-2-amino-1-(2-furyl)-1,3-butandiols

The synthesis of (1R, 2S, 3R) and (1S, 2S, 3R)-2-(N-benzoylamino)-1-(2-furyl)-1, 3-butandiols (15) and (16) from D-threonine is described. The assignment of absolute configuration of the newly formed asymmetric center at C-1 was based on the ¹H-NMR spectra of O-isopropylidene derivatives 17 and 18.     

Stereospecific synthesis of conjugated (1E,3E)- and (1Z,3Z)-1,4-di(n-N,N-dimethylaminophenyl)-1,3-butadienes from 2-chloro-1-(n-N,N-dimethylaminophenyl)ethenes: fluorescence properties

The conjugated 1,4-di(n-N,N-dimethylaminophenyl)-1,3-butadienes (n=o-, m-, p-) were efficiently synthesised by homocoupling of the appropriate 2-chloro-1-(n-N,N-dimethylaminophenyl)ethene (n=o-, m-, p-) with stoichiometric amounts of zerovalent nickel complexes. The 1,3-butadienes were obtained as a mixture of stereoisomers, with independence of the starting E or Z chlorovinyl isomer. Moreover, the stereospecific (Z,Z) stereoisomer was obtained by partial hydrogenation of the corresponding 1,3-butadiyne, while the stereospecific (E,E) stereoisomer was obtained by exposure to the sunlight radiation of the (Z,Z) or the (Z,E) compound in ethanol.     

Acanthellin-1, an unique isonitrile sesquiterpene from the sponge Acanthella acuta

A number of unique isonitrile sesquiterpenes have been isolated from the sponge Acanthella acuta. One of them acanthellin-1, with antimicrobial activity, is shown to be 1 with a 4-epi-eudesmane skeleton.     

Marine natural products: synthetic aspects

An overview of marine natural products synthesis during 2006 is provided. As with earlier installments in this series, the emphasis is on total syntheses of molecules of contemporary interest, new total syntheses, and syntheses that have resulted in structure confirmation or stereochemical assignments.     

Marine natural products: synthetic aspects

An overview of marine natural products synthesis during 2004 is provided. As with the previous installment of this series, the emphasis is on total syntheses of molecules of contemporary interest, new total syntheses, and syntheses that have resulted in structure confirmation or stereochemical assignments.     

Dictyodendrins A-E,the first telomerase-inhibitory marine natural products from the sponge Dictyodendrilla verongiformis

Five new alkaloids, dictyodendrins A-E (1-5), were isolated from the Japanese marine sponge Dictyodendrilla verongiformis as telomerase inhibitors. Their structures were elucidated by spectroscopic and chemical methods. Dictyodendrins are tyramine-based pyrrolocarbazole derivatives containing three or four p-hydroxybenzene groups. They inhibited telomerase completely at a concentration of 50 microg/mL.     

Chemistry of renieramycins. Part 7: Renieramycins T and U, novel renieramycin-ecteinascidin hybrid marine natural products from Thai sponge Xestospongia sp.

Two new bistetrahydroisoquinoline marine natural products, renieramycins T (1) and U (2), were isolated from the Thai blue sponge Xestospongia sp. and their structures were elucidated by comparing spectral data with those of renieramycin M (3a) and ecteinascidin 770 (4a). These compounds are the first reported examples of novel ecteinascidin-renieramycin hybrid natural products. Renieramycin T (1) showed strong cytotoxicity to several human cancer cell lines, its IC₅₀ values ranging from 4.7 to 98 nM.     

Stereospecific preparation of symmetrical (1Z, 3Z)- and (1E, 3E)-2,3-difluoro-1,4-disubstituted-buta-1,3-dienes from 1-bromo-1-fluoroalkenes

A straightforward method to prepare symmetrical (1Z, 3Z)- and (1E, 3E)-2,3-difluoro-1,4-disubstituted-buta-1,3-dienes is described. High E/Z ratio 1-bromo-1-fluoroalkenes, prepared by isomerization from the E/Z ≈ 1:1 isomeric mixtures, reacted with Bu₃SnSnBu₃ and Pd(PPh₃)₄ to afford (1Z, 3Z)-2,3-difluoro-1,4-disubstituted-buta-1,3-dienes in good yield. (Z)-1-Bromo-1-fluoroalkenes, which were prepared by kinetic reduction from 1-bromo-1-fluoroalkenes (E/Z ≈ 1:1), can undergo similar reaction with Bu₃SnSnBu₃ and Pd(PPh₃)₄/CuI to prepare (1E, 3E)-2,3-difluoro-1,4-disubstituted-buta-1,3-dienes.     

Amino-zinc-ene-enolate cyclisation: a short access to (2S,3R)- and (2S,3S)-3-benzylprolines (3-benzylpyrrolidine-2-carboxylic acids)

The synthesis of 3-benzylprolines can be easily achieved in a diastereoselective and enantioselective way via amino-zinc-ene-enolate cyclisation. Transmetalation of the cyclic zinc intermediate with Pd₂(dba)₃/P(o-Tolyl)₃ allowed functionalisation with an aromatic ring. One-pot hydrogenolysis and Boc-protection led to the cis-isomer readily usable for peptide synthesis. The trans-isomer was obtained by epimerisation of the α-centre in a sealed tube at 200 °C.     

Marine natural products: Deodactol,antineoplastic sesquiterpenoid from the sea hare aplysia dactylomela

Deodactol, a halogenated bisabolene-type sesquiterpene alcohol, has been isolated from the sea hare Aplysia dactylomela, and its structure and absolute configuration have been determined by X-ray diffraction. The compound crystallizes in the monoclinic system with the following crystal data: a=6.723(2), b = 11.838(1), c= 10.962(2) Å, β=99.41(2)°, V= 860.7; ?x= 1.669 g cm^?3 at ?135±2°C; space group P2₁. The structure was solved by the heavy-atom method from 3-dimensional diffractometer data collected at ?135±2°C using CuK_α radiation. The final R factor for 1854 reflections is 0.029. The absolute configuration of the molecule was determined by the “R Method” of Hamilton. Deodactol has a strong intramolecular OHO hydrogen bond bridging its tetrahydropyranyl and cyclohexanol rings. The alcohol shows moderate cytotoxic activity. The absolute configuration of deodactol corresponds to that of several halogenated chamigrenes and supports the proposed biogenetic hypothesis linking halogenated bisabolenes and chamigrenes.     

Synthesis of (+)-(1S,2R) and (−)-(1R,2S)-2-aminocyclobutane-1-carboxylic acids

(+)-(1S,2R) and (−)-(1R,2S)-2-aminocyclobutane-1-carboxylic acids have been prepared in >97% ee and in 33% and 20% overall yields starting from a single, chiral, bicyclic compound perceived as a chiral uracil equivalent. Construction of the cyclobutane ring is achieved via a [2+2] photocycloaddition reaction of this chiral precursor with ethylene.     

Stereoselective synthesis of (2R,3R) and (2R,3S)-3-hydroxyleucines

A stereoselective synthesis of (2R,3R) and (2R,3S)-3-hydroxyleucine is disclosed. The key step of the reaction sequence involves, stereo- and regioselective bromohydration of 7, using a brominating agent derived in situ from N-bromosuccinimide and 2,6-lutidine, via intramolecular sulfinyl group participation.     

Antioxidant benzylidene 2-aminoimidazolones from the Mediterranean sponge Phorbas topsenti

Three new benzylidene 2-aminoimidazolones, named phorbatopsins A-C, have been isolated from the Mediterranean marine sponge Phorbas topsenti, in addition to the known astaxanthin, adonirubin, taurine, and taurobetain. Their structures were elucidated through mass spectrometric and detailed 1D and 2D NMR spectroscopic data. The relative configuration of the molecules was determined on the basis of ¹H and ¹³C chemical shifts and proton-proton coupling constants. The absolute configuration of the chiral carbon C-6 of phorbatopsin B was determined by modified Mosher's method. The antioxidant activity, evaluated through the Oxygen Radical Absorbance Capacity (ORAC) assay, was also reported for the seven isolated compounds and structure-activity relationships are discussed. Phorbatopsin A appeared as the most active with an ORAC value of 0.88. Further investigations to support the promising antioxidant activity of phorbatopsin A will be followed.     

Lissoclibadins 1-3, three new polysulfur alkaloids, from the ascidian Lissoclinum cf. badium

Three new polysulfur alkaloids, lissoclibadins 1 (1)-3 (3), were isolated from the ascidian Lissoclinum sp. (cf. L. badium Monniot, F. and Monniot, C., 1996). The structures of 1-3 were assigned on the basis of their spectral data, and the computational modeling study was utilized for 1. Compound 1 had a trimeric structure of three identical aromatic anime moieties connected through two sulfide and a disulfide bonds. Compounds 2 and 3 were dimeric structures of the same unit as that of 1 connected through a sulfide and disulfide bonds (2) and two sulfide bonds (3). Compounds 1 and 2 inhibited the growth of the marine bacterium Ruegeria atlantica (15.2 mm at 20 μg/disk and 12.2 mm at 5 μg/disk, respectively) and 2 showed antifungal activity to Mucor hiemalis (13.8 mm at 50 μg/disk). Compounds 1-3 were cytotoxic against HL-60 (IC₅₀=0.37, 0.21, and 5.5 μM, respectively).     

Assymetric synthesis of (2S,3R)- and (2S,3S)-[2-C;3-H] glutamic acid

We have developed a synthetic route for (2S,3R)- and (2S,3S)-[2-¹³C;3-²H] glutamic acids with high enantioselectivity. The key reactions in this synthesis are the asymmetric reduction of the 2,3-didehydroornithine derivative using the (S,S)-Et-DuPHOS-Rh catalyst and the oxidation of the δ-position by ruthenium catalysis.