19098-31-8Relevant academic research and scientific papers
An improved heterogeneous asymmetric epoxidation of homoallylic alcohols using polymer-supported Ti(IV) catalysts
Karjalainen, Jaana K.,Hormi, Osmo E. O.,Sherrington, David C.
, p. 3895 - 3901 (1998)
Heterogeneous asymmetric epoxidation of homoallylic alcohols has been achieved using polymer-supported Ti(IV) catalysts with tert-butyl hydroperoxide as oxidant. The enantioselectivities and chemical yields obtained are significantly higher (ee values up to 80%) than with monomeric tartrate ligands.
Synthesis and Evaluation of Novel TLR2 Agonists as Potential Adjuvants for Cancer Vaccines
Lu, Benjamin L.,Williams, Geoffrey M.,Verdon, Daniel J.,Dunbar, P. Rod,Brimble, Margaret A.
supporting information, p. 2282 - 2291 (2019/10/02)
Cancer immunotherapy has gained increasing attention due to its potential specificity and lack of adverse side effects when compared to more traditional modes of treatment. Toll-like receptor 2 (TLR2) agonists are lipopeptides possessing the S-[2,3-bis(palmitoyloxy)propyl]-l-cysteine (Pam2Cys) motif and exhibit potent immunostimulatory effects. These agonists offer a means of providing "danger signals" in order to activate the immune system toward tumor antigens. Thus, the development of TLR2 agonists is attractive in the search of potential immunostimulants for cancer. Existing SAR studies of Pam2Cys with TLR2 indicate that the structural requirements for activity are, for the most part, very intolerable. We have investigated the importance of stereochemistry, the effect of N-terminal acylation, and homologation between the two ester functionalities in Pam2Cys-conjugated lipopeptides on TLR2 activity. The R diastereomer is significantly more potent than the S diastereomer and N-terminal modification generally lowers TLR2 activity. Most notably, homologation gives rise to analogues which are comparatively active to the native Pam2Cys containing constructs.
β-Hydroxy- A nd β-Aminophosphonate Acyclonucleosides as Potent Inhibitors of Plasmodium falciparum Growth
Cheviet, Thomas,Wein, Sharon,Bourchenin, Gabriel,Lagacherie, Manon,Périgaud, Christian,Cerdan, Rachel,Peyrottes, Suzanne
, p. 8069 - 8087 (2020/08/12)
Malaria is an infectious disease caused by a parasite of the genus Plasmodium, and the emergence of parasites resistant to all current antimalarial drugs highlights the urgency of having new classes of molecules. We developed an effective method for the synthesis of a series of β-modified acyclonucleoside phosphonate (ANP) derivatives, using commercially available and inexpensive materials (i.e., aspartic acid and purine heterocycles). Their biological evaluation in cell culture experiments and SAR revealed that the compounds' effectiveness depends on the presence of a hydroxyl group, the chain length (four carbons), and the nature of the nucleobase (guanine). The most active derivative inhibits the growth of Plasmodium falcIParum in vitro in the nanomolar range (IC50 = 74 nM) with high selectivity index (SI > 1350). This compound also showed remarkable in vivo activity in P. berghei-infected mice (ED50 ～0.5 mg/kg) when administered by the IP route and is, although less efficient, still active via the oral route. It is the first ANP derivative with such potent antimalarial activity and therefore has considerable potential for development as a new antimalarial drug.
PEPTIDE CONJUGATES, CONJUGATION PROCESS, AND USES THEREOF
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Page/Page column 136, (2019/03/17)
The invention relates to peptide conjugates, methods for making peptide conjugates, conjugates produced by the methods, and pharmaceutical compositions comprising the conjugates. Methods of eliciting immune responses in a subject and methods of vaccinating a subject, uses of the conjugates for the same, and uses of the conjugates in the manufacture of medicaments for the same are also contemplated.
AMINO ACID AND PEPTIDE CONJUGATES AND CONJUGATION PROCESS
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Page/Page column 133, (2017/09/09)
The invention relates to amino acid and peptide conjugates, methods for making amino acid and peptide conjugates, conjugates produced by the methods, and pharmaceutical compositions comprising the conjugates. Methods of eliciting immune responses in a subject and methods of vaccinating a subject, uses of the conjugates for the same, and uses of the conjugates in the manufacture of medicaments for the same are also contemplated.
Asymmetric Synthesis of Atorvastatin Calcium through Intramolecular Oxidative Oxygen-Nucleophilic Bromocyclization
Wu, Yan,Liu, Min-Jie,Huang, Hai-Qing,Huang, Guan-Xin,Xiong, Fang-Jun,Chen, Fen-Er
, p. 3681 - 3688 (2017/07/22)
The stereocontrolled synthesis of atorvastatin calcium starting from commercially available d-aspartic acid using an intramolecular oxidative oxygen-nucleophilic bromocyclization of a homoallylic tert-butyl carbonate is described. This strategy allows the formation of the chiral syn-1,3-diol moiety with the desired stereochemistry, and provides a functionalized bromomethyl group for the construction of the atorvastatin side-chain with high regio- and diastereoselectivity. This route is attractive as it represents an efficient and environmentally sensitive approach to the large-scale synthesis of statins and their analogues.
Design of a New Bimetallic Catalyst for Asymmetric Epoxidation and Sulfoxidation
Bhadra, Sukalyan,Akakura, Matsujiro,Yamamoto, Hisashi
supporting information, p. 15612 - 15615 (2016/01/09)
A new chiral tethered 8-quinolinol-based ligand class is developed. The binuclear titanium complex of the ligand operates through a novel mechanism allowing for the regio- and stereoselective epoxidation of primary and tertiary homoallylic alcohols (up to 98% ee), as well as first examples of 2-allylic phenols (up to 92% ee). The new catalyst system also promotes the asymmetric oxidation of γ-hydroxypropyl sulfides giving an important class of chiral sulfoxides that have been inaccessible to date (up to 95% ee).
Design, synthesis, biophysical and primer extension studies of novel acyclic butyl nucleic acid (BuNA)
Kumar, Vipin,Gore, Kiran R.,Pradeepkumar,Kesavan, Venkitasamy
, p. 5853 - 5865 (2013/09/12)
A novel nucleic acid analogue called acyclic (S)-butyl nucleic acid (BuNA) composed of an acyclic backbone containing a phosphodiester linkage and bearing natural nucleobases was synthesized. Next, (S)-BuNA nucleotides were incorporated in DNA strands and their effect on duplex stability and changes in structural conformation were investigated. Circular dichroism (CD), UV-melting and non-denatured gel electrophoresis (native PAGE) studies revealed that (S)-BuNA is capable of making duplexes with its complementary strands and integration of (S)-BuNA nucleotides into DNA duplex does not alter the B-type-helical structure of the duplex. Furthermore, (S)-BuNA oligonucleotides and (S)-BuNA substituted DNA strands were studied as primer extensions by DNA polymerases. This study revealed that the acyclic scaffold is tolerated by enzymes and is therefore to some extent biocompatible.
Acyclic butyl nucleic acid (BuNA): A novel scaffold for A-switch
Kumar, Vipin,Kesavan, Venkitasamy
, p. 19330 - 19340 (2013/10/22)
The construction of an A-switch, derived from the artificial nucleic acid called acyclic Butyl Nucleic Acid (BuNA) was accomplished. The phosphoramidite building blocks of (S)-BuNA were synthesized from (R)-aspartic acid. To demonstrate its use as an A-switch, a stretch of polyadenine nucleotides of (S)-BuNA was studied by circular dichroism (CD) and ultraviolet (UV) spectroscopy under neutral and acidic conditions. Acid-base titration revealed two state transitions at pH 4.8 and highly pH-dependent structural conformation reversibility. Thermal melting (Tm) studies suggest that at neutral pH, poly BuNA(A) is a weakly organized single strand, while at low pH it adopts a highly organized and rigid structure. Furthermore, MALDI-TOF-MS data revealed intermolecular interactions which led to the formation of an A-motif composed of a double helical structure. Since BuNA does not suffer from depurination under acidic conditions, this allowed us to determine the thermodynamic parameters of the A-motif. This is the first report of the construction of an A-switch using artificial nucleic acids.
Total synthesis of laulimalide: Synthesis of the northern and southern fragments
Trost, Barry M.,Seganish, W. Michael,Chung, Cheol K.,Amans, Dominique
supporting information; experimental part, p. 2948 - 2960 (2012/04/23)
The first stage in the development of a synthetic route for the total synthesis of laulimalide (1) is described. Our retrosynthetic analysis envisioned a novel macrocyclization route to the natural product by using a Ru-catalyzed alkene-alkyne coupling. This would be preceded by an esterification of the C19 hydroxyl group, joining together two equally sized synthons, the northern fragment 7 and the southern fragment 8. Our first generation approach to the northern fragment entailed a key sequential Ru/Pd coupling sequence to assemble the dihydropyran. The key reactions proceeded smoothly, but the inability to achieve a key olefin migration led to the development of an alternative route based on an asymmetric dinuclear Zn-catalyzed aldol reaction of a hydroxyl acylpyrrole. This key reaction led to the desired diol adduct 66 with excellent syn/anti selectivity (10:1), and allowed for the successful completion of the northern fragment 7. The key step for the synthesis of the southern fragment was a chemoselective Rh-catalyzed cycloisomerization reaction to form the dihydropyran ring from a diyne precursor. This reaction proved to be selective for the formation of a six-membered ring, over a seven. The use of an electron-deficient bidentate phosphine allowed for the reaction to proceed with a reduced catalyst loading. Making the pieces: The synthesis of two equal-sized fragments of laulimalide is described (see scheme). A key Rh-catalyzed cycloisomerization reaction allowed for an efficient synthesis of the endocyclic dihydropyran and a stereoselective acylpyrrole Zn-aldol reaction allowed for the formation of the syn-diol. Copyright
