Xn:Harmful;2432-99-7Relevant articles and documents
Syntheses of 12-aminododecanoic and 11-aminoundecanoic acids from vernolic acid
Ayorinde, Folahan O.,Nana, Erick Y.,Nicely, Pete D.,Woods, Anthony S.,Price, Elvis O.,Nwaonicha, Chukwuma P.
, p. 531 - 538 (1997)
12-Aminododecanoic acid and 11-aminoundecanoic acid, monomer precursors for nylon-12 and nylon-11, respectively, have been synthesized from vernolic (cis-12,13-epoxy-cis-9-octadecenoic) acid via a reaction sequence that includes the formation of 12-oxododecanoic acid oxime. Saponification of vernonia oil, followed by a low-temperature recrystallization at -20°C, gave 51% vernolic acid (97% purity, m.p. 23-25°C). Hydrogenation afforded cis-12,13-epoxystearic acid (m.p. 52-54°C, lit. m.p. 52-54°C), which upon oxidation with periodic acid in tertiary butyl alcohol gave 12-oxododecanoic acid with an isolated yield of 71.0%. Reaction of the oxoacid with hydroxylamine hydrochloride gave 12-oxododecanoic acid oxime, which was catalytically reduced to give 12-aminododecanoic acid with a yield greater than 85% and a melting point of 184-186°C (lit. m.p. 185-187C). 11-Aminoundecanoic acid was prepared from the 12-oxododecanoic acid oxime via a three-step reaction sequence that involved a Beckmann rearrangement, Hofmann degradation, and hydrolysis. Thus, the aldoxime acid was hydrolyzed in the presence of nickel acetate tetrahydrate to give 11-carbamoylundecanoic acid (48% yield, m.p. 129-131°C, lit. m.p. 129-130°C). The amide was then treated with a solution of sodium methoxide and bromine at 70-80°C to give 11-(methoxycarbonylamino)undecanoic acid at 75% yield (m.p. 84-86°C; elemental analysis, calculated for C13H25NO4: C, 60.19; H, 9.73; N, 5.40; O, 24.68%; found C, 60.02; H, 9.81; N, 5.26; O, 24.91%), which upon alkaline hydrolysis and subsequent neutralization gave 11-aminoundecanoic acid at 34% yield (m.p. 189-192°C, lit. m.p. 190°C). Mass spectrometric and 13C nuclear magnetic resonance data of the previously unreported 11-(methoxycarbonylamino)undecanoic acid is provided.
Self-Adjuvanting Cancer Vaccines from Conjugation-Ready Lipid A Analogues and Synthetic Long Peptides
Reintjens, Niels R. M.,Tondini, Elena,De Jong, Ana R.,Meeuwenoord, Nico J.,Chiodo, Fabrizio,Peterse, Evert,Overkleeft, Herman S.,Filippov, Dmitri V.,Van Der Marel, Gijsbert A.,Ossendorp, Ferry,Codée, Jeroen D. C.
supporting information, p. 11691 - 11706 (2020/11/26)
Self-adjuvanting vaccines, wherein an antigenic peptide is covalently bound to an immunostimulating agent, have been shown to be promising tools for immunotherapy. Synthetic Toll-like receptor (TLR) ligands are ideal adjuvants for covalent linking to peptides or proteins. We here introduce a conjugation-ready TLR4 ligand, CRX-527, a potent powerful lipid A analogue, in the generation of novel conjugate-vaccine modalities. Effective chemistry has been developed for the synthesis of the conjugation-ready ligand as well as the connection of it to the peptide antigen. Different linker systems and connection modes to a model peptide were explored, and in vitro evaluation of the conjugates showed them to be powerful immune-activating agents, significantly more effective than the separate components. Mounting the CRX-527 ligand at the N-terminus of the model peptide antigen delivered a vaccine modality that proved to be potent in activation of dendritic cells, in facilitating antigen presentation, and in initiating specific CD8+ T-cell-mediated killing of antigen-loaded target cells in vivo. Synthetic TLR4 ligands thus show great promise in potentiating the conjugate vaccine platform for application in cancer vaccination.
CONJUGATED CHEMICAL INDUCERS OF DEGRADATION AND METHODS OF USE
-
Page/Page column 438, (2020/05/28)
The subject matter described herein is directed to antibody-CIDE conjugates (Ab-CIDEs), to pharmaceutical compositions containing them, and to their use in treating diseases and conditions where targeted protein degradation is beneficial.
