26 research outputs found
A Merged Aldol Condensation, Alkene Isomerization, Cycloaddition/Cycloreversion Sequence Employing Oxazinone Intermediates for the Synthesis of Substituted Pyridines
A domino reaction sequence has been evaluated that begins with union of novel dihydrooxazinone precursors with 2-alkynyl-substituted benzaldehyde components through aldol condensation. Ensuing operations, including alkene isomerization, Diels-Alder, and retrograde Diels-Alder with loss of CO2 occurs in the same reaction vessel to provide polysubstituted tricyclic pyridine products
3,4-and 3,5-disubstituted 2-pyridones using an intermolecular cycloaddition/cycloreversion strategy: toward the synthesis of aristopyridinone A
The intermolecular cycloaddition of pyrazinone precursors with alkyne substrates was evaluated. The resulting regioisomeric [2.2.2]-diketopiperazine alkene cycloadducts were diverted into 2-pyridone products through cycloreversion of the [2.2.2]-bicyclic intermediates. New insights into the regioselectivity of pyrazinone azadiene Diels-Alder reactions as well as cycloreversion reactivity were revealed in this study. Synthetic sequences using this [4+2]/r[4+2] strategy were determined that can produce predominantly the 3,5-disubstituted 2-pyridone alkaloid structures; pyridones featuring the 3,4-substitution pattern are observed as the minor regioisomeric products. (C) 2015 Elsevier Ltd. All rights reserved
Analysis of the cercosporin polyketide synthase CTB1 reveals a new fungal thioesterase function
The polyketide synthase CTB1 is demonstrated to catalyze pyrone formation thereby expanding the known biosynthetic repertoire of thioesterase domains in iterative, non-reducing polyketide synthases
Intermolecular Diels-Alder Cycloaddition for the Construction of Bicyclo[2.2.2]diazaoctane Structures: Formal Synthesis of Brevianamide B and Premalbrancheamide
A stereoselective intermolecular Diels-Alder cycloaddition of an intermediate pyrazinone with both achiral and chiral acrylate-derived dienophiles provides rapid access to the bicyclo[2.2.2]diazaoctane core shared among several prenylated indole alkaloids. The product derived from cydoaddition with 2-nitroacrylate required an additional five to six synthetic operations to intercept established precursors to premalbrancheamide and brevianamide B. The chemistry detailed in this manuscript constitutes a formal total synthesis (12 steps each) of these [2.2.2]diazabicyclic natural products from proline methyl ester
Enantioselective Synthesis of (+)-Malbrancheamide B
The asymmetric total synthesis of the chlorinated [2.2.2]-diazabicyclic
indole alkaloid (+)-malbrancheamide B is reported. Key to the synthesis
is a domino reaction sequence that employs an aldol condensation,
alkene isomerization, and intramolecular Diels–Alder cycloaddition.
Diastereofacial selection between the azadiene stereofaces is enforced
with a chiral aminal auxiliary. A formal 7-step (longest linear route)
synthesis of (±)-malbrancheamide B is also reported
Synthesis and Spectrophotometric Analysis of 1-Azafluorenone Derivatives
A new extension for the ‘one pot’ construction of diverse 1-azafluorene derivatives featuring a Diels–Alder/retro-Diels–Alder cycloaddition is reported. Conditions were also determined for oxidation to the derived azafluorenones. The spectrophotometric analysis of five different azafluorenones were performed. Moderate fluorescence was observed with azafluorenone derivatives that bear an imbedded pyridone motif; whereas those bearing substituted pyridines do not fluoresce
Further Investigation of the Intermolecular Diels–Alder Cycloaddition for the Synthesis of Bicyclo[2.2.2]diazaoctane Alkaloids
The
convergent synthesis of bicyclo[2.2.2]Âdiazaoctane structures
using an intermolecular Diels–Alder cycloaddition between a
pyrazinone and commercially available fumarate or maleate precursors
is reported. High reactivity and stereoselection is observed with
both dienophile substrates. Structure validation was achieved by conversion
of cycloadducts into known [2.2.2]Âdiazabicyclic compounds or into
crystalline derivatives suitable for X-ray analysis. The cycloadduct
derived from reaction of pyrazinone and maleic anhydride underwent
selective anhydride ring opening and intersected an established precursor
in the synthesis of brevianamide B
The Stereochemical Course of Intramolecular Michael Reactions
We present a general model for understanding the stereochemical
course of intramolecular Michael reactions. We show that the addition
of β-ketoester enolates to α,β-unsaturated esters
and imides bearing adjacent stereocenters (X, Y = H, Me, OR) leads
to high levels of asymmetric induction. Reinforcing and nonreinforcing
stereochemical relationships are evaluated from the syn and anti reactant
diastereomers. On the basis of synthetic, spectroscopic, and computational
studies, we propose that the outcomes of these reactions can be rationalized
by a dipole-minimized chair transition-state model
Spectroscopic Evidence for Lactam Formation in Terminal Ornithine b(2)(+) and b(3)(+) Fragment Ions
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Efficient Entry to the [2.2.2]-Diazabicyclic Ring System via Diastereoselective Domino Reaction Sequence
A domino reaction sequence involving aldol condensation, alkene isomerization, and intramolecular hetero-Diels–Alder cycloaddition for the synthesis of [2.2.2]-diazabicyclic structures is reported. Excellent diastereofacial control during the cycloaddition is enforced with a removable chiral phenyl aminal diketopiperazine substituent. The reaction sequence rapidly generates molecular complexity and is competent with both enolizable and nonenolizable aldehyde substrates (nine examples total). Progress toward the synthesis of malbrancheamide B, a protypical member of the [2.2.2]-diazabicyclic natural product family, is also disclosed