5 research outputs found
Search for Conglomerate in Set of [7]Helquat Salts: Multigram Resolution of Helicene–Viologen Hybrid by Preferential Crystallization
Investigation of a set of 12 [7]helquat salts by X-ray
crystal diffraction led to identification of conglomerate behavior
in bis(trifluoroacetate) salt [<b>2</b>][CF<sub>3</sub>CO<sub>2</sub>]<sub>2</sub>. This is to demonstrate that a systematic search
for conglomerates can be performed for a given helicenoid enabling
straightforward multigram resolution via preferential crystallization.
Subsequently, preferential crystallization of this chiral helicene–viologen
hybrid has been established to obtain pure <i>P</i> and <i>M</i> enantiomers on a multigram scale, 5 g each. Furthermore,
preparation of nonracemic samples of [7]helquat <b>2</b> via
diastereomeric (<i>R</i>,<i>R</i>)-dibenzoyltartrate
salts is described, and determination of absolute configuration and
racemization barrier is also reported
Search for Conglomerate in Set of [7]Helquat Salts: Multigram Resolution of Helicene–Viologen Hybrid by Preferential Crystallization
Investigation of a set of 12 [7]helquat salts by X-ray
crystal diffraction led to identification of conglomerate behavior
in bis(trifluoroacetate) salt [<b>2</b>][CF<sub>3</sub>CO<sub>2</sub>]<sub>2</sub>. This is to demonstrate that a systematic search
for conglomerates can be performed for a given helicenoid enabling
straightforward multigram resolution via preferential crystallization.
Subsequently, preferential crystallization of this chiral helicene–viologen
hybrid has been established to obtain pure <i>P</i> and <i>M</i> enantiomers on a multigram scale, 5 g each. Furthermore,
preparation of nonracemic samples of [7]helquat <b>2</b> via
diastereomeric (<i>R</i>,<i>R</i>)-dibenzoyltartrate
salts is described, and determination of absolute configuration and
racemization barrier is also reported
An Ultimate Stereocontrol in Asymmetric Synthesis of Optically Pure Fully Aromatic Helicenes
The
role of the helicity of small molecules in enantioselective
catalysis, molecular recognition, self-assembly, material science,
biology, and nanoscience is much less understood than that of point-,
axial-, or planar-chiral molecules. To uncover the envisaged potential
of helically chiral polyaromatics represented by iconic helicenes,
their availability in an optically pure form through asymmetric synthesis
is urgently needed. We provide a solution to this problem present
since the birth of helicene chemistry in 1956 by developing a general
synthetic methodology for the preparation of uniformly enantiopure
fully aromatic [5]-, [6]-, and [7]helicenes and their functionalized
derivatives. [2 + 2 + 2] Cycloisomerization of chiral triynes combined
with asymmetric transformation of the first kind (ultimately controlled
by the 1,3-allylic-type strain) is central to this endeavor. The point-to-helical
chirality transfer utilizing a traceless chiral auxiliary features
a remarkable resistance to diverse structural perturbations
Nonpyrogenic Molecular Adjuvants Based on norAbu-Muramyldipeptide and norAbu-Glucosaminyl Muramyldipeptide: Synthesis, Molecular Mechanisms of Action, and Biological Activities in Vitro and in Vivo
Fatty
acyl analogues of muramyldipeptide (MDP) (abbreviated <i>N</i>-L18 norAbuGMDP, <i>N</i>-B30 norAbuGMDP, norAbuMDP-Lys(L18),
norAbuMDP-Lys(B30), norAbuGMDP-Lys(L18), norAbuGMDP-Lys(B30), B30
norAbuMDP, L18 norAbuMDP) are designed and synthesized comprising
the normuramyl-l-α-aminobutanoyl (norAbu) structural
moiety. All new analogues show depressed pyrogenicity in both free
(micellar) state and in liposomal formulations when tested in rabbits
in vivo (sc and iv application). New analogues are also shown to be
selective activators of NOD2 and NLRP3 (inflammasome) in vitro but
not NOD1. Potencies of NOD2 and NLRP3 stimulation are found comparable
with free MDP and other positive controls. Analogues are also demonstrated
to be effective in stimulating cellular proliferation when the sera
from mice are injected sc with individual liposome-loaded analogues,
causing proliferation of bone marrow-derived GM-progenitors cells.
Importantly, vaccination nanoparticles prepared from metallochelation
liposomes, His-tagged antigen rOspA from Borrelia burgdorferi, and lipophilic analogue norAbuMDP-Lys(B30) as adjuvant, are shown
to provoke OspA-specific antibody responses with a strong Th1-bias
(dominance of IgG2a response). In contrast, the adjuvant effects of
Alum or parent MDP show a strong Th2-bias (dominance of IgG1 response)
Nonpyrogenic Molecular Adjuvants Based on norAbu-Muramyldipeptide and norAbu-Glucosaminyl Muramyldipeptide: Synthesis, Molecular Mechanisms of Action, and Biological Activities in Vitro and in Vivo
Fatty
acyl analogues of muramyldipeptide (MDP) (abbreviated <i>N</i>-L18 norAbuGMDP, <i>N</i>-B30 norAbuGMDP, norAbuMDP-Lys(L18),
norAbuMDP-Lys(B30), norAbuGMDP-Lys(L18), norAbuGMDP-Lys(B30), B30
norAbuMDP, L18 norAbuMDP) are designed and synthesized comprising
the normuramyl-l-α-aminobutanoyl (norAbu) structural
moiety. All new analogues show depressed pyrogenicity in both free
(micellar) state and in liposomal formulations when tested in rabbits
in vivo (sc and iv application). New analogues are also shown to be
selective activators of NOD2 and NLRP3 (inflammasome) in vitro but
not NOD1. Potencies of NOD2 and NLRP3 stimulation are found comparable
with free MDP and other positive controls. Analogues are also demonstrated
to be effective in stimulating cellular proliferation when the sera
from mice are injected sc with individual liposome-loaded analogues,
causing proliferation of bone marrow-derived GM-progenitors cells.
Importantly, vaccination nanoparticles prepared from metallochelation
liposomes, His-tagged antigen rOspA from Borrelia burgdorferi, and lipophilic analogue norAbuMDP-Lys(B30) as adjuvant, are shown
to provoke OspA-specific antibody responses with a strong Th1-bias
(dominance of IgG2a response). In contrast, the adjuvant effects of
Alum or parent MDP show a strong Th2-bias (dominance of IgG1 response)