Efficient synthesis of tyrosine-derived marine sponge metabolites via acylation of amines with a coumarin

Condensation of N-acetylglycine with aldehyde 15 in acetic anhydride gave acetamido coumarin 16. Hydrolysis to the enol coumarin 17 and reaction with hydroxylamine gave the oximino coumarin 18. Reaction of the oximino coumarin 18 with a range of nucleophiles gave the phenolic oximes in excellent yield. The rates of acylation of histamine with the oximino coumarin 18 and methyl ester 9 were compared. Oxidative spirocyclization of three representative phenolic oximes with polymer-supported (diacetoxyiodo) benzene gave the spiroisoxazolines.     

Efficient total synthesis of bastadin 6, an anti-angiogenic brominated tyrosine-derived metabolite from marine sponge

An efficient total synthesis of bastadin 6 (1), a cyclic tetramer of brominated tyrosine derivatives from the marine sponge, Ianthella basta, with selective anti-angiogenic activity, was accomplished. We developed a novel Ce(IV)-mediated oxidative coupling reaction of 2,6-dibromophenols to give the diaryl ether derivatives, the characteristic segment of 1. Condensation of two segments and subsequent intramolecular macrocyclization gave bastadin 6 (1) in nine steps, 26% overall yield.     

Total synthesis of the marine sponge metabolites (+)-rottnestol, (+)-raspailol A and (+)-raspailol B

The asymmetric syntheses of (+)-rottnestol (1) and the related marine sponge metabolites (+)-raspailols A (5) and B (6) are described. The key step in each of these sequences was a Stille coupling to form the C9-C10 sp2-sp2 bond and connect the polyene sidechains to the appropriate optically active tetrahydropyran core. For rottnestol (1), both C12 epimers were synthesised by a coupling between stannane 7 and (R)- or (S)-8 followed by acid hydrolysis which allowed for the assignment of the absolute configuration at the remote C12 stereocentre as R upon comparison of chiroptical data of the synthetic material with that reported for the natural product. In accord with this, (12R)-raspailol A (5) was synthesised from stannane 7 and sidechain 9 and this compound also compared well with the data for natural material including sign and absolute value of the specific rotation. Finally, the same C12 epimer of raspailol B (6) was secured via a union between stannane 10 and iodide 9 and this also possessed a similar rotation to that described for the natural product. Thus, all three compounds appear to possess the (12R) configuration, while that of the core tetrahydropyran ring is the same as proposed originally.     

Brominated tyrosine-derived metabolites from the sponge Ianthella basta

Two novel metabolites, containing four bromotyrosine units, have been isolated from the sponge $\text{Ianthella basta}$.     

海绵生理活性物质研究新进展

本文综述了海绵中大环内酯、生物碱、肽类、萜类、甾醇等五类具有抗菌、抗病毒、抗肿瘤、抗爱滋病以及心血管活性等作用的生理活性物质的研究新进展     

Total synthesis of agosterol A: an MDR-modulator from a marine sponge

The first total synthesis of agosterol A, a modulator of multidrug resistance (MDR) mediated by P-gp and MRP1, and isolated from a marine sponge, was achieved from ergosterol by utilizing a regioselective epoxy-cleavage reaction and regioselective dehydroxylation as the key reactions.     

Asymmetric synthesis of cytotoxic sponge metabolites R-strongylodiols A and B

The asymmetric synthesis of the marine sponge natural products, R-strongylodiols A 1 and B 2 using a minimum protection strategy is described. The chirality of the natural products was introduced via the Noyori asymmetric reduction of ynones.     

Pseudoceratins A and B, antifungal bicyclic bromotyrosine-derived metabolites from the marine sponge Pseudoceratina purpurea

Pseudoceratins A (1) and B (2) have been isolated from the marine sponge Pseudoceratina purpurea. Pseudoceratins are unique among the large class of bromotyrosine-derived sponge metabolites with respect to the substitution pattern of aromatic rings and the presence of spiroacetal and oxime ether functional groups as well as an 1,5-diamino-1,5-dideoxy-D-arabitol tether. Pseudoceratins A (1) and B (2) are epimeric differing in the orientation of the tether. Their structures were determined by analysis of spectral data. The rigidity of the compounds arising from their bridged structure gave ROESY/NOESY spectra with many transannular cross-peaks, which allowed the assignment of the relative stereochemistry of 1 and 2 to be established. The d-configuration of the 1,5-diamino-1,5-dideoxyarabitol unit was determined by converting the fragment isolated from the acid hydrolysate to the Mosher's ester and compared the 1H NMR spectrum with those of standard samples. Pseudoceratins exhibited significant antifungal activity against Candida albicans.     

A short biomimetic synthesis of marine sponge alkaloid Pyrinadine A

The biomimetic synthesis of the marine sponge alkaloid Pyrinadine A, based on the oxidative dimerisation of hydroxylamine, is reported.     

Syntheses of two cytotoxic polyunsaturated pyrrole metabolites of the marine sponge Mycale micracanthoxea

Starting from eicosapentaenoic acid (EPA) the marine, naturally occurring, pyrrole derivatives, mycalazol 5 and mycalazal 2 have been synthesized. The Stille coupling reaction is a key step in the syntheses.     

Mycapolyols A-F, new cytotoxic metabolites of mixed biogenesis from the marine sponge Mycale izuensis

[structure: see text]. Mycapolyols A-F (1-6), six new unusual PKS/NRPS metabolites, were isolated from the marine sponge Mycale izuensis. The gross structures were elucidated by analysis of spectroscopic data, while the stereochemistry was established using chemical method and the universal NMR database.     

Biosynthetic pathways to dichloroimines; precursor incorporation studies on terpene metabolites in the tropical marine sponge Stylotella aurantium

The biosynthetic origin of the dichloroimine functional group in the marine sponge terpene metabolites stylotellanes A (3) and B (4) was probed by the use of [(14)C]-labelled precursor experiments. Incubation of the sponge Stylotella aurantium with [(14)C]-labelled cyanide or thiocyanate resulted in radioactive terpenes in which the radiolabel was shown by hydrolytic chemical degradation to be associated specifically with the dichloroimine carbons. Additionally, label from both precursors was incorporated into farnesyl isothiocyanate (2). A time course experiment with [(14)C]-cyanide revealed that the specific activity for farnesyl isothiocyanate decreases over time, but increases for stylotellane B (4), consistent with the rapid formation of farnesyl isothiocyanate (2) from inorganic precursors followed by a slower conversion to stylotellane B (4). The advanced precursors farnesyl isothiocyanate (2) and farnesyl isocyanide (5) were supplied to S. aurantium, and shown to be incorporated efficiently into stylotellane A (3) and B (4). Feeding of [(14)C]-farnesyl isothiocyanate (2) resulted in a higher incorporation of label than with [(14)C]-farnesyl isocyanide (5). Farnesyl isocyanide was incorporated into farnesyl isothiocyanate in agreement with labelling studies in other marine sponges. Both farnesyl isocyanide and isothiocyanate were further incorporated into axinyssamide A (11) as well as the cyclized dichloroimines (12)-(14), (16) that represent more advanced biosynthetic products of this pathway. These results identify the likely biosynthetic pathway leading to the major metabolites of S. aurantium.     

Convergent strategies for the total synthesis of polycyclic ether marine metabolites

Marine polycyclic ether natural products continue to fascinate chemists and biologists due to their exceptionally large and complex molecular architectures and potent and diverse biological activities. Tremendous progress has been made over the past decade toward the total synthesis of marine polycyclic ether natural products. In this area, a convergent strategy for assembling small fragments into an entire molecule always plays a key role in successful total synthesis. This review describes our efforts to develop convergent strategies for the synthesis of polycyclic ethers and their application to the total synthesis of gambierol, gymnocin-A, and brevenal, and to the partial synthesis of the central part of ciguatoxins and the nonacyclic polyether skeleton of gambieric acids.     

Carbohydrate-based synthesis of naturally occurring marine metabolites slagenins B and C

[reaction: see text] The first enantioselective syntheses of slagenins B and C, marine metabolites from Agelas nakamurai, starting from L-arabinose have been described.     

Total synthesis of marine sponge bis(indole) alkaloids of the topsentin class

The synthesis of four natural bis(indole) alkaloids of topsentin class 1 and 2 is described. Their bis(indole) alpha-carbonylimidazoline and subsequently bis(indole) alpha-carbonylimidazole moieties have been built via the condensation between indolic alpha-ketothioimidate salts 4 and 1-(indol-3'-yl)-1,2-diaminoethane 3. This compound results from the beta-amino indolic hydroxylamine 5 by a two-step sequence. This is the first total synthesis of compounds 1d, 2a, and 2b.     

Asymmetric synthesis of cytotoxic sponge metabolites R-strongylodiols A and B and an analogue

The asymmetric synthesis of the marine sponge natural products R-strongylodiols A R-1 and B R-2, using a minimum protection strategy, is described. Two approaches were examined and the Noyori asymmetric reduction of ynones was found to be successful for installing the chirality of the natural products. Analogue R-32 was also prepared. In addition, asymmetric alkynylation of aldehydes is briefly reviewed.