The first total synthesis and absolute stereochemistry of plakortone G from the Jamaican sponge Plakortis sp.

Total synthesis of plakortone G (1), a secondary metabolite of the Jamaican sponge Plakortis sp., was successfully achieved. The absolute configuration of this molecule was determined by comparison of the synthetic diastereomers with reported data to possess the (4R,8R)-configuration 14.     

Total synthesis of natural (+)-membrenone C and its 7-epimer

Highly stereoselective asymmetric total syntheses of the polypropionate marine defense substance (+)-membrenone C and its 7-epimer have been achieved. Highlights of the strategy include the utilization of a desymmetrization technique to create five contiguous chiral centres from a single bicyclic precursor.     

Total synthesis of (+)-FR-900493 and establishment of its absolute stereochemistry

The first total synthesis of (+)-FR-900493, an antibacterial nucleoside antibiotic possessing a 6′-N-alkyl-5′-O-aminoribosyl-glycyluridine structure, is described, and its relative and absolute stereochemistries were established. Key elements of the approach include the early-stage introduction of the aminoribose moiety and two sequential reductive alkylations of an amino group at the 6′-position. This synthetic strategy could be applicable to the synthesis of related nucleoside antibiotics, such as the more potent antibacterial nucleoside antibiotics, muraymycins.     

Plakoridine C, a novel piperidine alkaloid from an Okinawan marine sponge Plakortis sp.

A new piperidine alkaloid plakoridine C (1) has been isolated from an Okinawan marine sponge Plakortis species, and the structure was elucidated from spectroscopic data. Plakoridine C (1) is a new alkaloid possessing a piperidine ring connected to a β-keto-γ-lactone through a double bond.     

Njaoamines A-F, new cytotoxic polycyclic alkaloids from the haplosclerid sponge Reniera sp.

Six new cytotoxic polycyclic alkaloids containing an 8-hydroxyquinoline moiety, njaoamines A-F (1-6), have been isolated from the 2-propanol extract of the sponge Reniera sp. collected in Tanzania. Their structures were determined by extensive analysis of their spectroscopic features, particularly 1D and 2D NMR spectra recorded in Py-d₅. Cytotoxicity of the compounds isolated was evaluated against a panel of three human tumor cell lines.     

Bromine-containing alkaloids from the marine sponge Penares sp.

Two new unusual alkaloids were isolated from the sponge Penares sp., collected from Viet Nam waters (the South China Sea). The structures of these compounds were established by analysis of 1D, 2D NMR (¹H-¹H COSY, DEPT, HSQC, HMBC, H2BC, and NOE), and MS data. Compound 1 shows moderate cytotoxicity against the human tumor cells HL-60 and HeLa.     

Stereoselective synthesis of (+)-boronolide and its 8-epimer

Starting from readily available carbohydrates the synthesis of 8-epi-(+)-boronolide 19 and (+)-boronolide was achieved with diastereoselective propargylation of alpha-oxygenated aldehyde as a key step.     

Manzamine B and C,two novel alkaloids from the sponge haliclona sp.

The title compounds were isolated from a marine sponge collected off Okinawa. Their structures were determined by X-ray and shown to be 1-β-carbolines. Manzamine C was the 2-ethyl-N-azacycloundec-6-ene derivative, whereas manzamine B was more complex being the epoxy isomer of the free base of dihydromanzamine A.     

Dictyoneolone,a B/C ring juncture-defused steroid from a Dictyonella sp. sponge

Dictyoneolone (1), a new secosteroid was isolated from a Dictyonella sp. sponge collected from Gageo-do, Korea. Based upon the results of combined spectroscopic analyses, the structure of this compound was determined to possess a highly unusual B/C ring juncture-defused moiety. The configurations of 1 were determined by a combination of proton-proton couplings and NOESY analyses. Dictyoneolone exhibited weak cytotoxicity against the K562 and A549 cancer cell lines.     

Benzosceptrin C, a new dimeric bromopyrrole alkaloid from sponge Agelas sp.

A new dimeric bromopyrrole alkaloid possessing a benzocyclobutane ring, benzosceptrin C (1), has been isolated from an Okinawan marine sponge of the genus Agelas (SS-956), and the structure and relative stereochemistry were elucidated from spectroscopic data. Benzosceptrin C (1) showed antimicrobial activity.     

Total synthesis of (+)-phorboxazole A, a potent cytostatic agent from the sponge Phorbas sp

A convergent total synthesis of phorboxazole A (1a), from the C(3-19), C(20-27) and C(33-46) fragments 5, 4 and 91, respectively, concentrating on stereocontrolled formation of the bonds at C(2-3), C(19-20) and C(27-28), is described. Although a coupling reaction between a macrolide ketone and the side chain substituted sulfone, at C(27-28) was not successful, a Wadsworth-Emmons olefination involving the oxane methyl ketone 4 and an oxazole produced the oxane 90 which was next coupled to 91 leading to the C(20-46) unit 100. A further coupling of 100 to 71c at C(19-20) then led to 105, ultimately, and the synthesis was completed by a macrocyclisation reaction from 105, at the C(2-3) alkene bond, followed by deprotection of 106.     

Total synthesis of (+)-xyloketal D, a secondary metabolite from the mangrove fungus Xylaria sp.

(+)-Xyloketal D was prepared in a one-pot multistep domino reaction by heating optically active 5-hydroxy-4-methyl-3-methylenepentan-2-one (R) in toluene with 2,4-dihydroxyacetophenone. The absolute configuration of the natural product was confirmed by preparation of the starting enone from a lactone of established absolute configuration.     

Halichonadins G-J, new sesquiterpenoids from a sponge Halichondria sp.

Three new dimeric sesquiterpenoids, halichonadins G-I (1-3), and one new eudesmane sesquiterpenoid possessing a 1-phenethyl urea moiety, halichonadin J (4), were isolated from a marine sponge Halichondria sp. Halichonadins G (1) and H (2) are homo-dimers of eudesmane sesquiterpenoid, linked through a methyl 2-{1-(2-amino-2-oxoethyl)ureido}acetate fragment and a 2-hydroxymalonamide fragment, respectively, while halichonadin I (3) is a new hetero-dimer of eudesmane sesquiterpenoid linked through a urea fragment. The structures of 1-4 were elucidated on the basis of spectroscopic data.     

Agelasines O-U, new diterpene alkaloids with a 9-N-methyladenine unit from a marine sponge Agelas sp.

New diterpene alkaloids, agelasines O-U (1-7), have been isolated from an Okinawan marine sponge Agelas sp. The gloss structures and relative stereochemistries of 1-7 were elucidated from the spectroscopic data. Agelasines O-R (1-4) were the third examples of diterpene alkaloid with a 9-N-methyladenine and a pyrrole units. Agelasine O (1) has a halimane skeleton, while agelasines P-R (2-4) have a clerodane skeleton. Agelasines S-U (5-7) were new diterpene alkaloids with a 9-N-methyladenine unit consisting of a halimane skeleton, a labdane skeleton, and a clerodane skeleton, respectively. Agelasines O-R (1-4) and T (6) showed antimicrobial activities against several bacteria and fungi.     

Njaoamines G and H, two new cytotoxic polycyclic alkaloids and a tetrahydroquinolone from the marine sponge Neopetrosia sp.

Two new polycyclic alkaloids, njaoamines G (1) and H (2) and 1,2,3,4-tetrahydroquinolin-4-one (3) have been isolated from the sponge Neopetrosia sp. collected at Pemba Island, Tanzania. Compounds 1 and 2 are close in structure to njaoamines A-F. Compound 3, known synthetically, is a new natural compound. The structures and relative stereochemistries of compounds 1 and 2 were elucidated on the basis of spectroscopic data. Njaoamines G and H are potent brine shrimp toxins with LD₅₀ values of 0.17 μg/mL and 0.08 μg/mL for 1 and 2, respectively.     

Total synthesis of lycoperdic acid and its C4-epimer

Efficient stereodivergent syntheses of (+)-lycoperdic acid (LPA) and 4-epi-LPA have been achieved based on asymmetric hydrogenation (H₂, Rh/(R,S)-MeBoPhoz) of racemic enamide as a key step.     

Isolation and synthesis of N-acyladenine and adenosine alkaloids from a southern Australian marine sponge, Phoriospongia sp.

Chemical fractionation of the southern Australian marine sponge Phoriospongia sp. (CMB-03107) yielded phorioadenine A (1) as a nematocidal agent and the first reported example of a 6-N-acyladenine natural product. The structure of 1 was confirmed by spectroscopic analysis and the chemical synthesis of racemic (1a) and enantiomeric (1b) analogues. HPLC–ESIMS analysis of the crude sponge extract with comparisons to the synthetic 6-N-acyladenosine 2a provided evidence that the biosynthetically related adenosine, phorioadenosine A (2), was present as a trace co-metabolite. The rare starfish metabolite asterubine (3) was also isolated as a co-metabolite, and its structure confirmed by spectroscopic analysis and chemical synthesis. Biological investigations confirmed that natural products 1–3 and synthetic analogues 1a–e and 2a were not cytotoxic to multiple mammalian cancer cell lines, or Gram-positive or -negative bacteria. Nematocidal activity (inhibition of larval development of Haemonchus contortus) detected in the Phoriospongia sp. extract was attributed to 1 (LD₉₉ 31 μg/mL), with preliminary structure–activity relationship investigations confirming the importance of the N-acyl side chain.     

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.     

First total synthesis of parvistone C and its C8-epimer

Diastereoselective first total synthesis of parvistone C 1 and C8-epimer 1a are described. The key features of our synthesis include Sharpless asymmetric dihydroxylation, stereoselective aryl Grignard reactions, Still–Gennari olefination, and intramolecular cyclization.