76282-48-9Relevant articles and documents
Stereoselective synthesis of resorcylic acid lactone Cochliomycin B
Nagalatha,Siva Ganesh,Venkat Narsaiah
, (2021/09/22)
The total synthesis of 14-membered resorcylic acid lactone, Cochliomycin B has prescribed, in a convergent manner, from readily available starting materials, D-galactose, L-aspartic acid and ethyl acetoacetate. The key reactions involved in the synthesis are Julia-Kocienski olefination, E-selective Horner-Wadsworth-Emmons olefination and intramolecular lactonization.
Stereoselective total synthesis of obolactones and 7′,8′-dihydroobolactones
Fernandes, Rodney A.,Kumar, Praveen,Saini, Deepak
, p. 18976 - 18982 (2021/10/29)
A concise stereoselective total synthesis of two diastereomeric obolactones and 7′,8′-dihydroobolactones has been achieved using a metal-free catalytic δ-hydroxyalkynone rearrangement, which could provide the required dihydro-γ-pyrone moiety. The desired first stereogenic center was installed through the chiral pool material,l-aspartic acid. Next, the allylation reaction was strategically utilized to provide the requisite olefin bond for the intended ring-closing metathesis, allowing the installation of the remaining dihydro-α-pyrone moiety in the natural products. It also enabled the targeting of both dihydro-α-pyrone diastereomers. Thus, the first stereoselective total synthesis of (+)-7′,8′-dihydroobolactone was accomplished, establishing its structure and absolute configuration.
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.
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.
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).
Synthesis and structure-activity studies of the V-ATPase inhibitor saliphenylhalamide (SaliPhe) and simplified analogs
Garcia-Rodriguez, Jose,Mendiratta, Saurabh,White, Michael A.,Xie, Xiao-Song,De Brabander, Jef K.
supporting information, p. 4393 - 4398 (2015/10/12)
An efficient total synthesis of the potent V-ATPase inhibitor saliphenylhalamide (SaliPhe), a synthetic variant of the natural product salicylihalamide A (SaliA), has been accomplished aimed at facilitating the development of SaliPhe as an anticancer and antiviral agent. This new approach enabled facile access to derivatives for structure-activity relationship studies, leading to simplified analogs that maintain SaliPhe's biological properties. These studies will provide a solid foundation for the continued evaluation of SaliPhe and analogs as potential anticancer and antiviral agents.
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.
