Total synthesis and evaluation of [Psi[CH2NH]Tpg4]vancomycin aglycon: reengineering vancomycin for dual D-Ala-D-Ala and D-Ala-D-Lac binding

Journal of the American Chemical Society
Brendan M Crowley, Dale L Boger

Abstract

An effective synthesis of [Psi[CH(2)NH]Tpg(4)]vancomycin aglycon (5) is detailed in which the residue 4 amide carbonyl of vancomycin aglycon has been replaced with a methylene. This removal of a single atom was conducted to enhance binding to D-Ala-D-Lac, countering resistance endowed to bacteria that remodel their D-Ala-D-Ala peptidoglycan cell wall precursor by a similar single atom change (ester O for amide NH). Key elements of the approach include a synthesis of the modified vancomycin ABCD ring system featuring a reductive amination coupling of residues 4 and 5 for installation of the deep-seated amide modification, the first of two diaryl ether closures for formation of the modified CD ring system (76%, 2.5-3:1 kinetic atropodiastereoselectivity), a Suzuki coupling for installation of the hindered AB biaryl bond (90%) on which the atropisomer stereochemistry could be thermally adjusted, and a macrolactamization closure of the AB ring system (70%). Subsequent DE ring system introduction enlisted a room-temperature aromatic nucleophilic substitution reaction for formation of the remaining diaryl ether (86%, 6-7:1 kinetic atropodiastereoselectivity), completing the carbon skeleton of 5. Consistent with expectations and relat...Continue Reading

References

Jan 1, 1997·Medicinal Research Reviews·A MalabarbaR C Thompson
Jan 1, 1999·Bioorganic & Medicinal Chemistry Letters·D L BogerS L Castle
Jul 18, 2001·Journal of the American Chemical Society·D L BogerJ J McAtee
Sep 20, 2001·Current Medicinal Chemistry·A Malabarba, R Ciabatti
Oct 2, 2001·Medicinal Research Reviews·D L Boger
Oct 25, 2001·The Journal of Organic Chemistry·Dale L. BogerOlivier Loiseleur
Jan 25, 2002·Annual Review of Pharmacology and Toxicology·Jeff PootoolalGerard D Wright
Apr 5, 2002·Chembiochem : a European Journal of Chemical Biology·Roderich D Süssmuth
Apr 20, 2002·Bioorganic & Medicinal Chemistry Letters·J Jeffrey McAteeDale L Boger
Feb 22, 2003·Angewandte Chemie·Brian K Hubbard, Christopher T Walsh
Aug 2, 2003·Journal of the American Chemical Society·Casey C McComasDale L Boger
Apr 1, 2004·Journal of the American Chemical Society·Brendan M CrowleyDale L Boger
Feb 11, 2005·Chemical Reviews·Dan KahneChristopher Walsh
Oct 16, 1998·Angewandte Chemie·David A EvansJeffrey L Katz
Oct 16, 1998·Angewandte Chemie·K C NicolaouJoshi M Ramanjulu

❮ Previous
Next ❯

Citations

Mar 14, 2012·Biochemistry·Marc A BoudreauShahriar Mobashery
Feb 15, 2012·ACS Chemical Biology·Robert C JamesDale L Boger
May 18, 2010·Journal of the American Chemical Society·Hiroyuki ShimamuraDale L Boger
Oct 14, 2011·Journal of the American Chemical Society·Steven P Breazzano, Dale L Boger
May 25, 2012·Journal of the American Chemical Society·Brandon S FowlerScott J Miller
Jan 10, 2013·Journal of the American Chemical Society·Steven P BreazzanoDale L Boger
Oct 21, 2009·Journal of the American Chemical Society·Joie GarfunkleDale L Boger
Jun 8, 2010·Journal of Medicinal Chemistry·Jed F Fisher, Shahriar Mobashery
Sep 22, 2010·Journal of Medicinal Chemistry·Christine M CraneDale L Boger
Aug 27, 2013·Expert Opinion on Therapeutic Patents·Eugenia N Olsufyeva, Maria N Preobrazhenskaya
Oct 30, 2014·The Journal of Antibiotics·Venkateswarlu YarlagaddaJayanta Haldar
Dec 23, 2016·Expert Opinion on Drug Discovery·Hong YaoJinyi Xu
Feb 23, 2017·The Journal of Organic Chemistry·Takeo SakaiYuji Mori
Apr 25, 2017·Chemical Reviews·Akinori OkanoDale L Boger
Oct 11, 2016·Biochemical Pharmacology·Rustam Aminov
Feb 3, 2016·Angewandte Chemie·Erika A Crane, Karl Gademann
Jan 9, 2009·Bioorganic & Medicinal Chemistry Letters·Siegfried S F LeungWilliam L Jorgensen
Dec 17, 2009·Angewandte Chemie·John B BremnerDavid I Rhodes
Jun 14, 2017·Proceedings of the National Academy of Sciences of the United States of America·Steven L Castle
Jun 1, 2017·Proceedings of the National Academy of Sciences of the United States of America·Akinori OkanoDale L Boger
Sep 17, 2013·Angewandte Chemie·Kieron M G O'ConnellDavid R Spring
Jul 6, 2014·Angewandte Chemie·Peter M WrightAndrew G Myers
Dec 6, 2017·Microbial Biotechnology·Carlos Molina-SantiagoDiego Romero
Apr 25, 2006·Chemistry : a European Journal·Yanxing JiaJieping Zhu
Jul 29, 2006·Angewandte Chemie·Mark S BetsonSimon Peace
Aug 2, 2006·Angewandte Chemie·Franz von NussbaumDieter Häbich
Sep 14, 2006·Chemistry : a European Journal·Carsten SchmuckWolfgang Wienand
Apr 24, 2008·Chemistry : a European Journal·Davide MoianiCarsten Schmuck
Jan 9, 2009·Angewandte Chemie·K C NicolaouAnthony A Estrada
Apr 2, 2009·Organogenesis·Lauren S SefcikEdward A Botchwey
Aug 11, 2011·Chemical Society Reviews·Polly-Anna Ashford, Sean P Bew
Oct 22, 2013·Natural Product Reports·Armin Bauer, Mark Brönstrup
Nov 2, 2019·The Journal of Biological Chemistry·Edward MarschallJulien Tailhades
Nov 16, 2010·Angewandte Chemie·Alex M Szpilman, Erick M Carreira
Oct 3, 2006·Pharmazie in unserer Zeit·Ulrike Holzgrabe, Edith Bennack
Dec 6, 2008·Journal of Combinatorial Chemistry·Nicole Jung, Stefan Bräse

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bacterial Cell Wall Structure (ASM)

Bacterial cell walls are made of peptidoglycan (also called murein), which is made from polysaccharide chains cross-linked by unusual peptides containing D-amino acids. Here is the latest research on bacterial cell wall structures.

Bacterial Cell Wall Structure

Bacterial cell walls are made of peptidoglycan (also called murein), which is made from polysaccharide chains cross-linked by unusual peptides containing D-amino acids. Here is the latest research on bacterial cell wall structures.