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>]­[CF₃CO₂]₂. 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>]­[CF₃CO₂]₂. 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)