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ABSTRACT: The enantiomer of the bicyclic lomaiviticin aglycone A core was prepared via a two-directional, divergent approach featuring (1) a double Ireland Claisen rearrangement to establish key core bonds with correct relative stereochemistry and (2) a double olefin metathesis reaction to deliver both cyclohexene rings of the target.
The Journal of Organic Chemistry 04/2013; · 4.45 Impact Factor
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ABSTRACT: The bicyclic core of ent-lomaiviticin A was prepared in 11 operations from (S)-1-phenyl-2-propyn-1-ol in a two-directional route that features (1) a double Ireland Claisen rearrangement and (2) a double olefin metathesis reaction to form the key C-C bonds of the target.
Organic Letters 10/2012; · 5.86 Impact Factor
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ABSTRACT: We report herein that the oroidin-derived alkaloids palau'amine (1), dibromophakellin (2), and dibromophakellstatin (3) inhibit the proteolytic activity of the human 20S proteasome as well as the (i)20S immunoproteasome catalytic core. Palau'amine is found to prevent the degradation of ubiquitinylated proteins, including IκBα, in cell culture, which may be indicative of the potential mechanism by which these agents exhibit their exciting cytotoxic and immunosuppressive properties.
Journal of Natural Products 05/2012; 75(5):980-5. · 3.13 Impact Factor
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ABSTRACT: The bis indole sponge alkaloid dragmacidin E was synthesized in racemic form over 25 steps starting from 7-benzhydroxyindole. Key steps include (a) a Witkop cyclization to facilitate construction of the indole-spanning seven-membered ring and (b) a cyclodehydrative pyrazinone synthesis that unites the two indole-containing sectors.
Organic Letters 09/2011; 13(20):5704-7. · 5.86 Impact Factor
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ABSTRACT: Exploratory oxidative cyclization studies on cyclopentanelated and cyclohexenelated oroidin derivatives utilized Pummerer chemistry to generate pentacyclic structures related to the palau'amine family of sponge metabolites. Stereochemical issues were paramount, and appropriate choice of annelated ring size led to formation of the pentacyclic framework with complete diastereoselectivity for all of the core bonds.
The Journal of Organic Chemistry 06/2011; 76(12):5042-60. · 4.45 Impact Factor
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ABSTRACT: The conversion of a cycloheptannelated indole platform into the heptacyclic core structure of dragmacidin E proceeded over nine steps. Key sequences include a cyclocondensation to form an intermediate dihydropyrazinone ring and the conversion of a cyclic urea into the cyclic guanidine of the target.
Organic Letters 10/2010; 12(20):4502-5. · 5.86 Impact Factor
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ABSTRACT: A pentacyclic model system featuring the trans azabicyclo[3.3.0]octane unit of dibromopalau'amine was prepared with complete diastereoselectivity in the polycyclic core from a tricyclic precursor. The key transformations of this sequence include (a) a Pummerer reaction-mediated oxidative bicyclization, and (b) a Wolff rearrangement-based ring contraction to deliver the strained azabicyclo[3.3.0]octane core.
Organic Letters 10/2010; 12(20):4532-5. · 5.86 Impact Factor
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ABSTRACT: Collaborative work between experimentalists and computational chemists have demonstrated a stong synergy which allowed the rationalization of allenyl azide chemistry and permited the development of an efficient synthetic tool aimed at the preparation of several alkaloids. Saturated allenyl azides undergo a reaction cascade involving key diradical intermediates that follow the Curtin-Hammett model whereas unsaturated allenyl azides form indolidene intermediates that furnish the final indole products via electrocyclic ring closure events taking place out of the Curtin-Hammett regime. The regiochemistry of the reaction cascade with the latter substrates can be manipulated by Cu(I) addition to the reaction mixture.
Current Organic Chemistry 09/2010; 14(15):1646-1657. · 3.06 Impact Factor
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ABSTRACT: The base-mediated bicyclization of unsymmetrical bispropargyl sulfones furnishes varying yields of dihydroisobenzothiophene dioxides through a presumed diradical intermediate. Attempts to trap a putative thiophene dioxide intermediate via Diels-Alder reaction with a pendant alkyne were not successful.
Heterocycles 01/2010; 81(1):117-143. · 1.00 Impact Factor
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ABSTRACT: The thermal, photochemical, and photochemical/CuI-mediated cascade cyclizations of a range of substituted 1-(2-azidophenyl)-3-alkenylallenes are described. These reactions provide both 1,2- and 2,3-cyclopentennelated indole products in varying ratios. In most cases, high regioselectivity for the 2,3-annelated isomer can be achieved under the hnu/CuI conditions. Computational studies of this multistep reaction support the intermediacy of indolidene intermediates whose electrocyclizations (with or without copper present) define the regioselectivity branch point in the sequence.
The Journal of Organic Chemistry 06/2009; 74(14):4958-74. · 4.45 Impact Factor
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ABSTRACT: The sponge-derived alkaloid dibromoagelaspongin was prepared from a dihydrooroidin derivative by exploiting the Pummerer reaction twice in succession. Oxidative cyclization of the substrate's pyrrole-2-carboxamide function into the imidazole moiety was achieved in a regiospecific manner to establish both C-N bonds to C(6) of the target.
The Journal of Organic Chemistry 04/2009; 74(9):3449-61. · 4.45 Impact Factor
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ABSTRACT: Detailed studies of the thermal conversion of 1-azidohepta-3,4,6-trienes into cyclopentennelated dihydropyrroles are presented. High levels of diastereoselectivity and regioselectivity are documented. A mechanistic proposal that accounts for all of the diverse results is developed through the use of density functional calculations. These calculations provide support for the intervention of unexpected mechanistic subtleties, such as the planarity of an azatrimethylenemethane diyl intermediate and an apparent Woodward-Hoffmann-type electrocyclization of a five-atom diyl array.
The Journal of Organic Chemistry 08/2008; 73(13):5090-9. · 4.45 Impact Factor
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ABSTRACT: Irradiation of 2-(3-alkenyl)allenylphenyl azides in the presence of excess CuI furnished functionalized 2,3-cyclopentenylindoles in good yield with only trace amounts of competitive C-N-bonded regioisomeric products. These results represent a significant departure from the modest-to-nonexistent regioselectivity that attended thermal cyclization of these allenyl azide substrates.
Organic Letters 05/2008; 10(8):1665-8. · 5.86 Impact Factor
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ABSTRACT: The pentacyclic base of the sponge-derived alkaloid lihouidine has been assembled from two quinoline fragments. The key step is a nitration-promoted cyclization to form the C-C bond between the two quinoline units.
Tetrahedron Letters 04/2008; 49(13):2136-2138. · 2.68 Impact Factor
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ABSTRACT: The syntheses of (+/-)-dibromophakellstatin and, from this species, (+/-)-dibromophakellin are described. Oxidative cyclization of a phenylthiolated dihydrooroidin derivative triggered by a Pummerer reaction constitutes the key step in this biomimetic approach to this family of marine alkaloids.
The Journal of Organic Chemistry 11/2007; 72(21):8076-86. · 4.45 Impact Factor
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ABSTRACT: A series of 11 simple phylloquinone derivatives, each lacking the extended phytyl side chain but featuring H-bond donor amides at one or both peri positions, were prepared and some salient physical properties were measured. A correlation between both IR frequency and NMR peak position, as indicators of internal H-bond strength, and the quinone half-wave reduction potential, was observed. These data are consistent with the prevailing hypothesis that quinone carbonyl H-bonding in general, and stronger H-bonds in particular, favorably bias the endogenous quinone's electrochemical potential toward easier reduction.
Bioorganic & Medicinal Chemistry Letters 10/2007; 17(17):4891-4. · 2.55 Impact Factor
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ABSTRACT: A density functional theory based computational approach to describing the mechanistic course of the allene azide cycloaddition cascade sequence has been developed. The results of these calculations permit characterization of key reactive intermediates (diradicals and/or indolidenes) and explain the different behaviors observed in the experimental studies between conjugated and nonconjugated species. Furthermore, computational analysis of certain intermediates offer insight into issues of regioselectivity and stereoselectivity in cases where different reaction channels are in competition, suggesting suitable substitutions to achieve a single regioisomer in the indole synthesis via azide-allene cyclization.
Journal of the American Chemical Society 07/2007; 129(24):7638-46. · 9.91 Impact Factor
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ABSTRACT: The putative reductive activation chemistry of the diazoparaquinone antibiotics was modeled with Bu(3)Sn-H and prekinamycin dimethyl ether along with prekinamycin itself. Reaction in various combinations of aromatic solvents, with and without the nucleophile benzylmercaptan present, led to isolation of both radical-trapping arene adducts and nucleophilic capture benzyl thioether products. On the basis of these product distribution studies, the intermediacies of, first, a cyclopentenyl radical and, next, an orthoquinonemethide electrophile are postulated.
Journal of the American Chemical Society 10/2006; 128(38):12562-73. · 9.91 Impact Factor
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ABSTRACT: The conversion of (Ss)-3-(omega-allylsilane and silyl enol ether)indole-2-sulfoxides to spirocyclic indolenines and then to oxindoles proceeds, in favorable cases, with moderate levels of chirality transfer from sulfur to C3 of the indole core. A mechanistic model, which features either an Sn2'-like additive Pummerer sequence or a tight ion pair generated by an Sn1-like vinylogous Pummerer transform, is proposed to rationalize the sense of asymmetric induction.
Organic Letters 09/2006; 8(18):4137-40. · 5.86 Impact Factor
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ABSTRACT: [reaction: see text] Thermolysis of 2-(allenyl)phenyl azides leads to a cascade cyclization sequence furnishing both C(2)-C(3) and N-C(2) cyclopentannelated indoles.
Organic Letters 08/2006; 8(14):3113-6. · 5.86 Impact Factor
