12 research outputs found
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 cyclopentaÂ[<i>g</i>]Âindoles 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
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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><sup>α</sup>-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><sup>2</sup>,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><sup>2</sup>,3-ethenoguanine (5-methyl-7-isopropyl-4,5-dihydroimidazo[2,1-<i>b</i>]purine). Additional properties of acremolin are also described including its <sup>1</sup>H–<sup>15</sup>N-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 <sup>13</sup>C NMR signals in samples at the nanomole-scale
that arise from Cl-substituted <sup>13</sup>C by exploiting the <sup>35</sup>Cl/<sup>37</sup>Cl isotope shift
Structures and Solution Conformational Dynamics of Stylissamides G and H from the Bahamian Sponge <i>Stylissa caribica</i><sup></sup>
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 <sup>1</sup>H 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 (IC<sub>50</sub> 300
pM)