5 research outputs found
Competitive Pseudopericyclic [3,3]- and [3,5]-Sigmatropic Rearrangements of Trichloroacetimidates
The
Woodward–Hoffmann rules predict whether concerted pericyclic
reactions are allowed or forbidden based on the number of electrons
involved and whether the cyclic orbital overlap involves suprafacial
or antarafacial orbital overlap. Pseudopericyclic reactions constitute
a third class of reactions in which orthogonal orbitals make them
orbital symmetry allowed, regardless of the number of electrons involved
in the reaction. Based on the recent report of eight-centered ester
rearrangements, it is predicted that the isoelectronic eight-centered
rearrangements of imidates would also be allowed. We now report that
these rearrangements occur, and indeed, an eight-centered rearrangement
is slightly favored in at least one case over the well-known six-centered
Overman rearrangements, in a trichloroacetimidoylcyclohexadienone,
a molecular system where both rearrangements are possible
Competitive Pseudopericyclic [3,3]- and [3,5]-Sigmatropic Rearrangements of Trichloroacetimidates
The
Woodward–Hoffmann rules predict whether concerted pericyclic
reactions are allowed or forbidden based on the number of electrons
involved and whether the cyclic orbital overlap involves suprafacial
or antarafacial orbital overlap. Pseudopericyclic reactions constitute
a third class of reactions in which orthogonal orbitals make them
orbital symmetry allowed, regardless of the number of electrons involved
in the reaction. Based on the recent report of eight-centered ester
rearrangements, it is predicted that the isoelectronic eight-centered
rearrangements of imidates would also be allowed. We now report that
these rearrangements occur, and indeed, an eight-centered rearrangement
is slightly favored in at least one case over the well-known six-centered
Overman rearrangements, in a trichloroacetimidoylcyclohexadienone,
a molecular system where both rearrangements are possible
Experimental and Computational Studies on the [3,3]- and [3,5]-Sigmatropic Rearrangements of Acetoxycyclohexadienones: A Non-ionic Mechanism for Acyl Migration
Flash vacuum pyrolysis studies of
substituted 6-acetoxy-2,4-cyclohexadienones
(<b>3</b> and <b>10</b>) from 300 to 500 °C provide
strong experimental evidence that direct [3,5]-sigmatropic rearrangements
in these molecules are favored over the more familiar [3,3]-sigmatropic
rearrangements. The preference holds when the results are extrapolated
to 0.0% conversion, indicating that this is a concerted process. Pyrolysis
of 6,6-diacetoxy-2-methyl-2,4-cyclohexadienone (<b>9</b>) at
350 °C gives a modest yield of the initial [3,5]-sigmatropic
rearrangement product, 2,6-diacetoxy-6-methyl-2,4-cyclohexadienone
(<b>11</b>). Qualitative arguments and electronic structure
theory calculations are in agreement that the lowest energy pathway
for each [3,5]-sigmatropic rearrangement is via an allowed, concerted
pseudopericyclic transition state. The crystal structures of compounds <b>3</b>, <b>9</b>, and <b>10</b> prefigure these transition
states. The selectivity for the [3,5] products increases with an increasing
temperature. This unexpected selectivity is explained by a concerted,
intramolecular, and pseudopericyclic transition state (<b>TS-5</b>) that forms a tetrahedral interemediate (<i>ortho</i>-acid
ester <b>4′</b>), followed by similar ring openings to
isomeric phenols, which shifts the equilibrium toward the phenols
from the [3,5] (but not the [3,3]) products
Experimental and Computational Studies on the [3,3]- and [3,5]-Sigmatropic Rearrangements of Acetoxycyclohexadienones: A Non-ionic Mechanism for Acyl Migration
Flash vacuum pyrolysis studies of
substituted 6-acetoxy-2,4-cyclohexadienones
(<b>3</b> and <b>10</b>) from 300 to 500 °C provide
strong experimental evidence that direct [3,5]-sigmatropic rearrangements
in these molecules are favored over the more familiar [3,3]-sigmatropic
rearrangements. The preference holds when the results are extrapolated
to 0.0% conversion, indicating that this is a concerted process. Pyrolysis
of 6,6-diacetoxy-2-methyl-2,4-cyclohexadienone (<b>9</b>) at
350 °C gives a modest yield of the initial [3,5]-sigmatropic
rearrangement product, 2,6-diacetoxy-6-methyl-2,4-cyclohexadienone
(<b>11</b>). Qualitative arguments and electronic structure
theory calculations are in agreement that the lowest energy pathway
for each [3,5]-sigmatropic rearrangement is via an allowed, concerted
pseudopericyclic transition state. The crystal structures of compounds <b>3</b>, <b>9</b>, and <b>10</b> prefigure these transition
states. The selectivity for the [3,5] products increases with an increasing
temperature. This unexpected selectivity is explained by a concerted,
intramolecular, and pseudopericyclic transition state (<b>TS-5</b>) that forms a tetrahedral interemediate (<i>ortho</i>-acid
ester <b>4′</b>), followed by similar ring openings to
isomeric phenols, which shifts the equilibrium toward the phenols
from the [3,5] (but not the [3,3]) products
Conjugation of Amphiphilic Proteins to Hydrophobic Ligands in Organic Solvent
Protein–ligand
conjugations are usually carried out in aqueous
media in order to mimic the environment within which the conjugates
will be used. In this work, we focus on the conjugation of amphiphilic
variants of elastin-like polypeptide (ELP), short elastin (sEL), to
poorly water-soluble compounds like OPPVs (<i>p</i>-phenylenevinylene
oligomers), triarylamines, and polypyridine-metal complexes. These
conjugations are problematic when carried out in aqueous phase because
hydrophobic ligands tend to avoid exposure to water, which in turn
causes the ligand to self-aggregate and/or interact noncovalently
with hydrophobic regions of the amphiphile. Ultimately, this behavior
leads to low conjugation efficiency and contamination with strong
noncovalent “conjugates”. After exploring the solubility
of sEL in various organic solvents, we have established an efficient
conjugation methodology for obtaining covalent conjugates virtually
free of contaminating noncovalent complexes. When conjugating carboxylated
ligands to the amphiphile amines, we demonstrate that even when only
one amine (the N-terminus) is present, its derivatization is 98% efficient.
When conjugating amine moieties to the amphiphile carboxyls (a problematic
configuration), protein multimerization is avoided, 98–100%
of the protein is conjugated, and the unreacted ligand is recovered
in pure form. Our syntheses occur in “one pot”, and
our purification procedure is a simple workup utilizing a combination
of water and organic solvent extractions. This conjugation methodology
might provide a solution to problems arising from solubility mismatch
of protein and ligand, and it is likely to be widely applied for modification
of recombinant amphiphiles used for drug delivery (PEG-antibodies,
polymer-enzymes, food proteins), cell adhesion (collagen, hydrophobins),
synthesis of nanostructures (peptides), and engineering of biocompatible
optoelectronics (biological polymers), to cite a few