109075-73-2Relevant articles and documents
Structure–activity relationship study of hydroxyethylamine isostere and P1′ site structure of peptide mimetic BACE1 inhibitors
Kobayashi, Kazuya,Otani, Takuya,Ijiri, Saki,Kawasaki, Yuki,Matsubara, Hiroki,Miyagi, Takahiro,Kitajima, Taishi,Iseki, Risa,Ishizawa, Katsuyasu,Shindo, Naoka,Okawa, Kouta,Ueda, Kouta,Ando, Syun,Kawakita, Momoka,Hattori, Yasunao,Akaji, Kenichi
, (2021/10/27)
An aromatic substituent has been introduced into a known hydroxyethylamine (HEA)-type BACE1 inhibitor containing the superior substrate sequence to enhance inhibitory activity. The HEA-type isosteres bearing different hydroxyl group and methyl group confi
Probing α-Amino Aldehydes as Weakly Acidic Pronucleophiles: Direct Access to Quaternary α-Amino Aldehydes by an Enantioselective Michael Addition Catalyzed by Br?nsted Bases
García-Urricelqui, Ane,de Cózar, Abel,Mielgo, Antonia,Palomo, Claudio
supporting information, p. 2483 - 2492 (2020/12/25)
The high tendency of α-amino aldehydes to undergo 1,2-additions and their relatively low stability under basic conditions have largely prevented their use as pronucleophiles in the realm of asymmetric catalysis, particularly for the production of quaternary α-amino aldehydes. Herein, it is demonstrated that the chemistry of α-amino aldehydes may be expanded beyond these limits by documenting the first direct α-alkylation of α-branched α-amino aldehydes with nitroolefins. The reaction produces densely functionalized products bearing up to two, quaternary and tertiary, vicinal stereocenters with high diastereo- and enantioselectivity. DFT modeling leads to the proposal that intramolecular hydrogen bonding between the NH group and the carbonyl oxygen atom in the starting α-amino aldehyde is key for reaction stereocontrol.
Structurally Diverse Acyl Bicyclobutanes: Valuable Strained Electrophiles
Attard, Riley H.,Gardiner, Michael G.,Malins, Lara R.,Schwartz, Brett D.,Zhang, Meng Yao
supporting information, p. 2808 - 2812 (2020/03/04)
Bicyclo[1.1.0]butanes (BCBs) are highly strained carbocycles that have emerged as versatile synthetic tools, particularly for the construction of functionalized small molecules. This work reports two efficient pathways for the rapid preparation of over 20 structurally diverse BCB ketones, encompassing simple alkyl and aryl derivatives, as well as unprecedented amino acid, dipeptide, bioisostere, and bifunctional linchpin reagents currently inaccessible using literature methods. Analogues are readily forged in two steps and in high yields from simple carboxylic acids or through unsymmetrical ketone synthesis beginning with a convenient carbonyl dication equivalent. The utility of this novel toolbox of strained electrophiles for the selective modification of proteinogenic nucleophiles is highlighted.
α-Amino Aldehydes as Readily Available Chiral Aldehydes for Rh-Catalyzed Alkyne Hydroacylation
Hooper, Joel F.,Seo, Sangwon,Truscott, Fiona R.,Neuhaus, James D.,Willis, Michael C.
supporting information, p. 1630 - 1634 (2016/02/20)
Readily available α-amino aldehydes, incorporating a methylthiomethyl (MTM) protecting group on nitrogen, are shown to be efficient substrates in Rh-catalyzed alkyne hydroacylation reactions. The reactions are performed under mild conditions, employing a small-bite-angle bis-phosphine ligand, allowing for good functional group tolerance with high stereospecificity. Amino aldehydes derived from glycine, alanine, valine, leucine, phenylalanine, isoleucine, serine, tryptophan, methionine, and cysteine were successfully employed, as was an enantiomerically enriched α-OMTM-aldehyde derived from phenyllactic acid. The synthetic utility of the α-amino enone products is demonstrated in a short enantioselective synthesis of the natural product sphingosine.
PEPTIDOMIMETIC COMPOUNDS AND ANTIBODY-DRUG CONJUGATES THEREOF
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, (2015/07/07)
This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer.
Evaluation of transition-state mimics in a superior BACE1 cleavage sequence as peptide-mimetic BACE1 inhibitors
Hattori, Yasunao,Kobayashi, Kazuya,Deguchi, Ayaka,Nohara, Yukie,Akiyama, Tomomi,Teruya, Kenta,Sanjoh, Akira,Nakagawa, Atsushi,Yamashita, Eiki,Akaji, Kenichi
, p. 5626 - 5640 (2015/11/11)
A superior substrate sequence for BACE1 containing transition-state mimics at the scissile site was evaluated as a protease inhibitor. Hydroxymethylcarbonyl (HMC) and hydroxyethylamine (HEA) isosteres were selected as the transition state mimics, and inco
Systematic comparison of peptidic proteasome inhibitors highlights the α-ketoamide electrophile as an auspicious reversible lead motif
Stein, Martin L.,Cui, Haissi,Beck, Philipp,Dubiella, Christian,Voss, Constantin,Krueger, Achim,Schmidt, Boris,Groll, Michael
supporting information, p. 1679 - 1683 (2014/03/21)
The ubiquitin-proteasome system (UPS) has been successfully targeted by both academia and the pharmaceutical industry for oncological and immunological applications. Typical proteasome inhibitors are based on a peptidic backbone endowed with an electrophi
Three-step synthesis of cyclopropyl peptidomimetics
Dunlap, Norma,Lankford, Kevin R.,Pathiranage, Anuradha Liyana,Taylor, Jessica,Reddy, Nikhil,Gouger, Daniel,Singer, Phillip,Griffin, Kent,Reibenspies, Joseph
supporting information; experimental part, p. 4879 - 4881 (2011/12/05)
An efficient approach to novel cyclopropyl peptidomimetics has been developed. The synthetic route involves a cyclopropanation using ethyl (dimethylsulfuranylidene)acetate (EDSA) as the key step and affords a cyclopropyl peptidomimetic core in three steps
HIV protease-mediated activation of sterically capped proteasome inhibitors and substrates
Buckley, Dennis L.,Corson, Timothy W.,Aberle, Nicholas,Crews, Craig M.
supporting information; experimental part, p. 698 - 700 (2011/04/15)
Strategies for selectively killing HIV-infected cells present an appealing alternative to traditional antiretroviral drugs. We show here the first example of an inactive "Trojan horse" molecule that releases a cytotoxic, smallmolecule proteasome inhibitor upon cleavage by HIV-1 protease. As a proof-of-concept strategy, the protein avidin was used to block entry of the compound into the proteasome in the absence of HIV-1 protease. We demonstrate that this strategy is also feasible without requiring an exogenous protein; a polylysine dendrimer-containing molecule is unable to enter the proteasome until cleaved by HIV-1 protease. These results demonstrate that conditional proteasome inhibitors could prove useful in the development of new tools for chemical biology and future therapeutics.
Tin(ii) chloride assisted synthesis of N-protected γ-amino β-keto esters through semipinacol rearrangement
Bandyopadhyay, Anupam,Agrawal, Neha,Mali, Sachitanand M.,Jadhav, Sandip V.,Gopi, Hosahudya N.
supporting information; experimental part, p. 4855 - 4860 (2010/12/24)
A facile synthetic route for the preparation of N-protected γ-amino β-keto esters from amino aldehydes and ethyl diazoacetate is described. The two component coupling is facilitated by tin(ii) chloride followed by semipinacol rearrangement leading to the product in quantitative yield. The reaction is mild, instantaneous and compatible with Boc-, Fmoc- and Cbz-amino protecting groups.
