d‑Glucosamine-Derived Synthons for Assembly of l-<i>threo</i>-Sphingoid Bases. Total Synthesis of Rhizochalinin C

A five-step transformation of d-glucosamine, commencing with indium-mediated Barbier reaction without isolation of intermediates, into (<i>R</i>,<i>R</i>)-2-aminohex-5-ene-1,3-diol in 45–51% is described. The latter is a useful synthon for assembly of l-<i>threo</i>-sphingoid bases: long-chain aminoalkanols and aminoalkanediols with configurations antipodal to that found in mammalian D-<i>erythro</i>-sphingosine but prevalent among invertebrate-derived sphingolipids. The utility of the method is demonstrated by the first total synthesis of rhizochalinin C, the long-chain, “two-headed” sphingoid base aglycon of the natural product rhizochalin C from the marine sponge <i>Rhizochalina incrustata</i>

Six Trikentrin-like Cyclopentanoindoles from <i>Trikentrion flabelliforme</i>. Absolute Structural Assignment by NMR and ECD

Six new cyclopenta­[<i>g</i>]­indoles were isolated from a West Australian sponge, <i>Trikentrion flabelliforme</i> Hentschel, 1912, and their structures elucidated by integrated spectroscopic analysis. The compounds are analogues of previously described trikentrins, herbindoles, and trikentramides from related Axinellid sponges. The assignment of absolute configuration of the new compounds was carried out largely by comparative analysis of specific rotation, calculated and measured ECD, and exploiting van’t Hoff’s principle of optical superposition. Five of the new compounds were chemically interconverted to establish their stereochemical relationships, leading to a simple chiroptical mnemonic for assignment of the this family of chiral indoles. The first biosynthetic hypothesis is advanced to explain the origin of the trikentrin–herbinole family and proposes a pyrrole–carboxylic thioester-initiated polyketide synthase mechanism

Cyclic Hexapeptide Dimers, Antatollamides A and B, from the Ascidian Didemnum molle. A Tryptophan-Derived Auxiliary for l- and d‑Amino Acid Assignments

Two dimerized cyclic hexapeptides, antatollamides A (<b>1</b>) and B (<b>2</b>), were isolated from the colonial ascidian Didemnum molle collected in Pohnpei. The amino acid compositions and sequences were determined by interpretation of MS and 1D and 2D NMR data. Raney Ni reduction of antatollamide A cleaved the dimer to the corresponding monomeric cyclic hexapeptide with replacement of Cys by Ala. The amino acid configuration of <b>1</b> was established, after total hydrolysis, by derivatization with a new chiral reagent, (5-fluoro-2,4-dinitrophenyl)-<i>N</i>^α-l-tryptophanamide (FDTA), prepared from l-Trp, followed by LCMS analysis; all amino acids were found to be l-configured except for d-Ala

Resolution of Atropisomeric Cyclic Catechol Monoether <i>O</i>‑Sulfate Esters by a Molluscan Sulfatase

Atropisomeric cyclic catechol ethers are notoriously difficult to resolve by classical chiral phase high-performance liquid chromatography. Here, we show the first application of sulfatase enzymes for the kinetic resolution of <i>O</i>-sulfato-catechol ethers with enantioselectivities ranging from 30 to 65% ee, as determined by preparation of their Marfey’s ether derivatives. Substrate-structure dependence was briefly explored

Acremolin from <i>Acremonium strictum</i> is <i>N</i>²,3-Etheno-2′-isopropyl-1-methylguanine, not a 1<i>H</i>‑Azirine. Synthesis and Structural Revision

The first synthesis of the heterocyclic marine natural product, acremolin, is reported along with the revision of the structure from a 1<i>H</i>-azirine to a substituted <i>N</i>²,3-ethenoguanine (5-methyl-7-isopropyl-4,5-dihydroimidazo[2,1-<i>b</i>]purine). Additional properties of acremolin are also described including its ¹H–¹⁵N-HMBC and fluorescence spectra

Bioactive Bromotyrosine Alkaloids from the Bahamian Marine Sponge Aiolochroia crassa. Dimerization and Oxidative Motifs

Nine bromotyrosine alkaloids (BTAs), including debromoianthelline (1), pseudoceratinic acid (2a), methyl pseudoceratinate (2b), 13-oxo-ianthelline (3), aiolochroiamides A–D (4a,b and 5a,b), and 7-hydroxypurealidin J (6), were isolated from a Bahamian Aiolochroia crassa (Hyatt; previously, Pseudoceratina crassa). The structures of 1–6 were established from 1H, 13C, and 2D NMR spectra, IR, and mass spectrometry data. Compounds 2–4 comprise an O-methyl-2,6-dibromotyrosyl ketoxime (subunit A) amide linked to variable groups (subunit B). Compound 1 is debromoianthelline, and 2a and 2b are amides of 3-aminopropanoic acid and methyl 3-aminopropanoate, respectively. BTAs 3 and 4 are linked to 5-(2-aminoethyl)-2-iminoimidazolidin-4-one and a hexahydropyrrolo[2,3-d]imidazol-2(1H)-imine nucleus, respectively, whereas 5 is a self-dimerization motif of an aryl pyruvamide. Alkaloid 6 contains a spirocyclohexadienyl-isoxazoline-carboxamide amide coupled to 2-aminohistamine similar to that found in purealidin J and aerophobin-1 but with hydroxylation at C-7. The 2,4-diaminobutanoic acid residue in 3 was determined to be a 2:1 L- and D- mixture based on hydrolysis followed by derivatization with L-FDTA and LCMS. Diastereomeric pairs, 4a,b and 5a,b, were racemic. The relative configurations of 4a, 4b, 5a, and 5b were assigned by comparison of 1H and 13C chemical shifts with those calculated by DFT. Compounds 5a,b, ningalamide B (9), and ianthelline (7) moderately inhibited butyrylcholinesterase and Candida and Cryptococcus spp

Mollenynes B–E from the Marine Sponge <i>Spirastrella mollis</i>. Band-Selective Heteronuclear Single Quantum Coherence for Discrimination of Bromo–Chloro Regioisomerism in Natural Products

Four new chlorobromohydrins, mollenynes B–E, were isolated from the marine sponge <i>Spirastrella mollis</i> collected from Hogsty Reef, Bahamas. Their structures were elucidated by integrated analysis of NMR, MS, and computational methods. A high-resolution band-selective HSQC experiment was developed to identify ¹³C NMR signals in samples at the nanomole-scale that arise from Cl-substituted ¹³C by exploiting the ³⁵Cl/³⁷Cl isotope shift

Structures and Solution Conformational Dynamics of Stylissamides G and H from the Bahamian Sponge <i>Stylissa caribica</i>

Two new peptides, stylissamides G and H, were isolated from extracts of a sample of <i>Stylissa caribica</i> collected in deep waters of the Caribbean Sea. A single sample of <i>S. caribica</i> among a collection of 10 samples that were examined by LC-MS appeared to be a different chemotype from the others in that it lacked the familiar pyrrole-2-aminoimidazole alkaloids, stevensine and oroidin, and contained peptides of the stylissamide class. The structures of the title compounds were solved by integrated analysis of the MS and NMR spectra and chemical degradation. The solution conformation of stylissamide G was briefly examined by electronic circular dichroism and temperature-dependent ¹H NMR chemical shifts of amide NH signals, which supported a conformationally rigid macrocycle

Salvadenosine, a 5′-Deoxy-5′-(methylthio) Nucleoside from the Bahamian Tunicate <i>Didemnum</i> sp.

Salvadenosine, (<b>1</b>) a rare 5′-deoxy-5′-(methylthio) nucleoside, was isolated from the deep-water Bahaman tunicate <i>Didemnum</i> sp. The structure was solved by integrated analysis of MS and 1D and 2D NMR data. We revise the structure of the known natural product, hamiguanosinol, which is a constitutional isomer of <b>1</b>, to <b>5</b> by interpretation of the spectroscopic data and comparison with synthesized nucleosides

Symplocin A, a Linear Peptide from the Bahamian Cyanobacterium <i>Symploca</i> sp. Configurational Analysis of <i>N</i>,<i>N</i>-Dimethylamino Acids by Chiral-Phase HPLC of Naphthacyl Esters

The absolute stereostructures of the components of symplocin A (<b>3</b>), a new <i>N</i>,<i>N</i>-dimethyl-terminated peptide from the Bahamian cyanobacterium <i>Symploca</i> sp., were assigned from spectroscopic analysis, including MS, 2D NMR, and Marfey’s analysis. The complete absolute configuration of symplocin A, including the unexpected d-configurations of the terminal <i>N</i>,<i>N</i>-dimethylisoleucine and valic acid residues, was assigned by chiral-phase HPLC of the corresponding 2-naphthacyl esters, a highly sensitive, complementary strategy for assignment of N-blocked peptide residues where Marfey’s method is ineffectual or other methods fall short. Symplocin A exhibited potent activity as an inhibitor of cathepsin E (IC₅₀ 300 pM)