- Structurally Diverse Acyl Bicyclobutanes: Valuable Strained Electrophiles
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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.
- Attard, Riley H.,Gardiner, Michael G.,Malins, Lara R.,Schwartz, Brett D.,Zhang, Meng Yao
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supporting information
p. 2808 - 2812
(2020/03/04)
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- Binding cooperativity between a ligand carbonyl group and a hydrophobic side chain can be enhanced by additional H-bonds in a distance dependent manner: A case study with thrombin inhibitors
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One of the underappreciated non-covalent binding factors, which can significantly affect ligand-protein binding affinity, is the cooperativity between ligand functional groups. Using four different series of thrombin inhibitors, we reveal a strong positiv
- Said, Ahmed M.,Hangauer, David G.
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supporting information
p. 405 - 424
(2015/05/05)
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- Cu(I)-catalyzed synthesis of dihydropyrimidin-4-ones toward the preparation of β- And β3-amino acid analogues
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A copper(I)-catalyzed synthesis of substituted dihydropyrimidin-4-ones from propargyl amides via the formation of ketenimine intermediate has been successfully developed; the synthesis afforded good isolated yields (80-95%). The mild reaction conditions at room temperature allow the reaction to proceed to completion in a few hours without altering the stereochemistry. Further, by involving a variety of reactive nucleophiles, the obtained substituted dihydropyrimidin-4-ones were elegantly transformed into the corresponding β- and β3-amino acid analogues.
- Rajagopal, Basker,Chen, Ying-Yu,Chen, Chun-Chi,Liu, Xuan-Yu,Wang, Huei-Ren,Lin, Po-Chiao
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supporting information
p. 1254 - 1264
(2014/03/21)
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- Deglycobleomycin A6 analogues modified in the methylvalerate moiety
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Previous studies have indicated that the methylvalerate subunit of bleomycin (BLM) plays an important role in facilitating DNA cleavage by BLM and deglycoBLM. Eleven methylvalerate analogues have been synthesized and incorporated into deglycoBLM congeners by the use of solid-phase synthesis. The effect of the valerate moiety in the deglycoBLM analogues has been studied by comparison with the parent deglycoBLM A5 using supercoiled DNA relaxation and sequence-selective DNA cleavage assays. All of the deglycoBLM analogues were found to effect the relaxation of the plasmid DNA. Those analogues having aromatic C4-substituents exhibited cleavage efficiency comparable to that of deglycoBLM A5. Some, but not all, of the deglycoBLM analogues were also capable of mediating sequence-selective DNA cleavage.
- Cai, Xiaoqing,Zaleski, Paul A.,Cagir, Ali,Hecht, Sidney M.
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scheme or table
p. 3831 - 3844
(2011/08/02)
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- Synthesis of new (-)-bestatin-based inhibitor libraries reveals a novel binding mode in the S1 pocket of the essential malaria M1 metalloaminopeptidase
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The malarial PfA-M1 metallo-aminopeptidase is considered a putative drug target. The natural product dipeptide mimetic, bestatin, is a potent inhibitor of PfA-M1. Herein we present a new, efficient, and high-yielding protocol for the synthesis of bestatin derivatives from natural and unnatural N-Boc-d-amino acids. A diverse library of bestatin derivatives was synthesized with variants at the side chain of either the α-hydroxyβ-amino acid (P1) or the adjacent naturalα-amino acid (P1′). Surprisingly, we found that extended aromatic side chains at the P1 position resulted in potent inhibition against PfA-M1. To understand these data, we determined the X-ray cocrystal structures of PfA-M1 with two derivatives having either a Tyr(OMe) 15 or Tyr(OBzl) 16 at the P1 position and observed substantial inhibitor-induced rearrangement of the primary loop within the PfA-M1 pocket that interacts with the P1 side chain. Our data provide important insights for the rational design of more potent and selective inhibitors of this enzyme that may eventually lead to new therapies for malaria.
- Velmourougane, Geetha,Harbut, Michael B.,Dalal, Seema,McGowan, Sheena,Oellig, Christine A.,Meinhardt, Nataline,Whisstock, James C.,Klemba, Michael,Greenbaum, Doron C.
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experimental part
p. 1655 - 1666
(2011/05/16)
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- Preparation of α-hydroxy-β-Fmoc amino acids from N-Boc amino acids
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A general method for the conversion of N-Boc amino acids into their homologated α-hydroxy-β-Fmoc amino acids is described. The protocol involved preparation of the amino aldehyde by reduction of the corresponding Weinreb amides, hydrocyanation, and hydrol
- Johnson, Erik P.,Hubieki, M. Patricia,Combs, Andrew P.,Teleha, Christopher A.
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experimental part
p. 4023 - 4026
(2012/01/12)
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- β-isocupreidine-catalyzed Baylis-Hillman reaction of chiral N-Boc-α-amino aldehydes
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β-Isocupreidine (β-ICD)-catalyzed Baylis-Hillman reaction of chiral N-Boc-α-amino aldehydes and 1,1,1,3,3,3-hexafluoroisopropyl acrylate (HFIPA) takes place without racemization and exhibits the match-mismatch relationship between the substrate and the catalyst. In the case of acyclic amino aldehydes, α,-substrates show excellent syn selectivity and high reactivity in contrast to L-substrates. On the other hand, in the case of cyclic amino aldehydes, D-substrates rather than L-substrates show excellent anti selectivity and high reactivity.
- Nakano, Ayako,Takahashi, Keisuke,Ishihara, Jun,Hatakeyama, Susumi
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p. 5357 - 5360
(2007/10/03)
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- Antibiotic N′,N″-dibenzyleremomycin with a reduced 1,2-peptide bond
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Eremomycin derivatives with benzylated amino groups of both residues of eremosamine and with (R) or (S)-2-amino-4-methylpentyl substituted for N-methyl-D-Leu, the first amino acid residue of its heptapeptide, were synthesized in order to study the role of
- Printsevskaya,Olsuf'eva,Lazhko,Preobrazhenskaya
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- A Convenient and Versatile Synthesis of Chiral Aliphatic and Allylic Amines
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Preparation of optically pure aliphatic and allylic amines from amino acids is described.Wittig olefination of α-Boc-amino aldehydes affords Boc-prodected allylic amines which can be deprotected to the corresponding chiral unsaturated amines.Catalytic reduction of the Wittig product prior to deprotection affords aliphatic amines of high optical purity.
- Saari, Walfred S.,Fisher, Thorsten E.
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p. 453 - 454
(2007/10/02)
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