scholarly journals Foldamer-templated catalysis of macrocycle formation

Science ◽  
2019 ◽  
Vol 366 (6472) ◽  
pp. 1528-1531 ◽  
Author(s):  
Zebediah C. Girvin ◽  
Mary Katherine Andrews ◽  
Xinyu Liu ◽  
Samuel H. Gellman
Keyword(s):  
Bond Formation ◽  
Three Dimensional ◽  
Human Medicine ◽  
Ring Closure ◽  
Helical Conformation ◽  
Aldol Reactions ◽  
Amino Acid Residues ◽  
Ion Sensing ◽  
Carbon Carbon Bond ◽  
Intermolecular Reactions

Macrocycles, compounds containing a ring of 12 or more atoms, find use in human medicine, fragrances, and biological ion sensing. The efficient preparation of macrocycles is a fundamental challenge in synthetic organic chemistry because the high entropic cost of large-ring closure allows undesired intermolecular reactions to compete. Here, we present a bioinspired strategy for macrocycle formation through carbon–carbon bond formation. The process relies on a catalytic oligomer containing α- and β-amino acid residues to template the ring-closing process. The α/β-peptide foldamer adopts a helical conformation that displays a catalytic primary amine–secondary amine diad in a specific three-dimensional arrangement. This catalyst promotes aldol reactions that form rings containing 14 to 22 atoms. Utility is demonstrated in the synthesis of the natural product robustol.

scholarly journals Conformation and membrane interaction studies of the potent antimicrobial and anticancer peptide palustrin-Ca

2021 ◽  
Author(s):  
Patrick Brendan Timmons ◽  
Chandralal M Hewage
Keyword(s):  
Sodium Dodecyl ◽  
Three Dimensional ◽  
Dynamics Simulation ◽  
Peptide Sequence ◽  
Helical Conformation ◽  
Dimensional Structure ◽  
Amino Acid Residues ◽  
Anticancer Activities ◽  
American Bullfrog ◽  
Α Helix

Palustrin-Ca (GFLDIIKDTGKEFAVKILNNLKCKLAGGCPP) is a host defense peptide with potent antimicrobial and anticancer activities, first isolated from the skin of the American bullfrog Lithobates catesbeianus. The peptide is 31 amino acid residues long, cationic and amphipathic. Two-dimensional NMR spectroscopy was employed to characterise its three-dimensional structure in a 50/50% water/2,2,2-trifluoroethanol-d3 mixture. The structure is defined by an α-helix that spans between Ile6-Ala26, and a cyclic disulphide bridged domain at the C-terminal end of the peptide sequence, between residues 23 and 29. A molecular dynamics simulation was employed to model the peptide's interactions with sodium dodecyl sulphate micelles, a widely used bacterial membrane-mimicking environment. Throughout the simulation, the peptide was found to maintain its α-helical conformation between residues Ile6-Ala26, while adopting a position parallel to the surface to micelle, which is energetically-favourable due to many hydrophobic and electrostatic contacts with the micelle.

scholarly journals Catalytic Cascade Reactions Inspired by Polyketide Biosynthesis

2020 ◽  
Vol 74 (9) ◽  
pp. 699-703
Author(s):  
Daniel Moser ◽  
Alessandro Castrogiovanni ◽  
Dominik Lotter ◽  
Reto M. Witzig ◽  
Vincent C. Fäseke ◽  
...  
Keyword(s):  
Chemical Synthesis ◽  
Bond Formation ◽  
Cascade Reactions ◽  
Aldol Reactions ◽  
Biological Functions ◽  
Polyketide Biosynthesis ◽  
Stepwise Approach ◽  
Natural Systems ◽  
Carbon Carbon Bond ◽  
Enzymatic Machinery

Aldol reactions belong to the most important methods for carbon–carbon bond formation and are also involved in one of the most astonishing biosynthetic processes: the biosynthesis of polyketides governed by an extraordinarily sophisticated enzymatic machinery. In contrast to the typical linear or convergent strategies followed in chemical synthesis, this late-stage catalysis concept allows Nature to assemble intermediates that are diversified into a broad range of scaffolds, which assume various crucial biological functions. To transfer this concept to small-molecule catalysis to access products beyond the natural systems, a stepwise approach to differentiate increasingly complex substrates was followed by investigating arene-forming polyketide cyclizations. An outline of our efforts to develop and apply these concepts are presented herein.

Carbon−Carbon Bond Formation

2008 ◽  
Author(s):  
Jie Jack Li ◽  
Chris Limberakis ◽  
Derek A. Pflum
Keyword(s):  
Natural Products ◽  
Asymmetric Synthesis ◽  
Aldol Condensation ◽  
Bond Formation ◽  
Aldol Reaction ◽  
Aldol Reactions ◽  
Academic Press ◽  
Carbon Carbon Bond ◽  
Stereogenic Centers ◽  
Aldol Addition

Reviews: (a) Vicarion, J. L.; Badia, D.; Carillo, L.; Reyes, E.; Etxebarria, J. Curr. Org. Chem. 2005, 9, 219-235. (b) Mahrwald, R. Ed. In Modern Aldol Reactions; Wiley-VCH: Weinheim, 2004; Vol. 1., pp. 1-335 (c) Mahrwald, R. Ed. In Modern Aldol Reactions; Wiley-VCH: Weinheim, 2004; Vol. 2., pp. 1-345.(d) Machajewski, T. D.; Wong, C.-H. Angew. Chem. Int. Ed. 2000, 39, 1352-1375. (e) Carriera, E. M. In Modern Carbonyl Chemistry; Otera, J.; Wiley-VCH: Weinheim, 2000; Chapter 8: Aldol Reaction: Methodology and Stereochemistry, 227-248. (f) Paterson, I.; Cowden, C. J.; Wallace, D. J. In Modern Carbonyl Chemistry; Otera, J.; Wiley-VCH: Weinheim, 2000; Chapter 9: Stereoselective Aldol Reactions in the Synthesis of Polyketide Natural Products, pp. 249-298. (g) Franklin, A. S.; Paterson, I. Contemp. Org. Synth. 1994, 1 317-338. (h) Heathcock, C. H. In Asymmetric Synthesis; Morrison, J. D., Ed.; Academic Press: Orlando, Fl.; 1984; Vol. 3., Chapter 2: The Aldol Addition Reaction, pp. 111-212. (i) Mukaiyama, T. Org. React. 1982, 28, 203-331. Since the early 1980s, aldol condensations involving boron enolates have gain great importance in asymmetric synthesis, particularly the synthesis of natural products with adjacent stereogenic centers bearing hydroxyl and methyl groups. (Z)-Boron enolates tend to give a high diastereoslectivity preference for the syn-stereochemistry while (E)-boron enolates favor the anti-stereochemistry. Because the B-O and B-C bonds are shorter than other metals with oxygen and carbon, the six membered Zimmerman–Traxler transition state in the aldol condensation tends to be more compact which accentuates steric interactions, thus leading to higher diastereoselectivity. When this feature is coupled with a boron enolate bearing a chiral auxillary, high enantioselectivity is achieved. Boron enolates are generated from a ketone and boron triflate in the presence of an organic base such as triethylamine. Reviews: (a) Abiko, A. Acc. Chem. Res. 2004, 37, 387-395. (b) Cowden, C. J. Org. React. 1997, 51, 1-200.

An overview of Zn-catalyzed enantioselective aldol type C–C bond formation

RSC Advances ◽  
2015 ◽  
Vol 5 (76) ◽  
pp. 62179-62193 ◽  
Author(s):  
Amrutha P. Thankachan ◽  
S. Asha ◽  
K. S. Sindhu ◽  
Gopinathan Anilkumar
Keyword(s):  
Bond Formation ◽  
Aldol Reactions ◽  
Carbon Bond ◽  
Carbon Carbon Bond ◽  
Wide Range ◽  
Efficient Route ◽  
Type C

Enantioselective zinc-catalyzed aldol reactions provide an efficient route for the construction of a wide range of carbon–carbon bond-formation, which are described here.

scholarly journals DFT-Assisted Design and Evaluation of Bifunctional copper(I) Catalysts for the Direct Intermolecular Addition of Aldehydes and Ketones to Alkynes

2018 ◽  
Author(s):  
Jacob D. Porter ◽  
Eric Greve ◽  
Abdulmohsen Alsafran ◽  
Adam R. Benoit ◽  
Sergey V. Lindeman ◽  
...  
Keyword(s):  
Density Functional ◽  
Bond Formation ◽  
Bifunctional Catalysts ◽  
Nmr Studies ◽  
Tridentate Ligands ◽  
X Ray Crystallography ◽  
H Nmr ◽  
Carbon Carbon Bond ◽  
Aldehydes And Ketones ◽  
Intermolecular Reactions

Bifunctional catalysts containing discrete metal pi-acid and amine sites were designed and investigated for the direct intermolecular addition of aldehydes and ketones to unactivated alkynes. Despite prior reports of intramolecular (Conia-ene-type) reactions and confirmation here that Cu(I)-based catalysts are effective, NMR studies indicated that a dual catalytic approach using separate amine and pi-acid catalysts may not be feasible for intermolecular reactions due to undesirable enamine competition with alkynes for metal complexation. Bifunctional precatalysts were designed with tridentate ligands and potentially hemilabile heterocyclic spacers, expected to be suitable for the binding of pi-acidic metals such as copper (I) and silver (I). The structures of the designed catalysts were computed using density functional theory (DFT), and the relative energies of putative catalytic intermediates were estimated. The calculated free energy changes upon carbon–carbon bond formation were used to prioritize catalyst designs, and several modular precatalysts were selected and prepared, with a focus on thiazole-containing systems synthesized via a 9-step sequence. Catalysts were screened for the direct addition of aldehydes and ketones to several internal and terminal alkynes. The precatalysts were combined with several different transition metal salts, and their structures studied with <sup>1</sup>H NMR and x-ray crystallography. Despite the lack of observed intermolecular reactions, DFT calculations of putative catalyst intermediates appears to be a promising strategy for the design and prioritization of bifunctional catalysts for C–C bond formation, and the combined results suggest that more rigid complexes may be necessary to catalyze direct intermolecular additions of aldehydes/ketones to alkynes.

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