Reviews of the Anti-malarial agents

  1. Buchholz, Mailu, Boniface (2007; 3; 225-255) Frontiers in drug design and discovery (Book Series); Structure-Based Drug Development Against Malaria (Private Access)
  2. Doron Greenbaum (2002) A Funtional Proteomics Approach To Understand The Role Of Cysteine Proteases (Dissertation); Diss. Abstr. Int., B 2002, 63(4), 1699 (Private Access)
  3. Ramjee, Flynn,; Substrate mapping and inhibitor profiling of falcipain-2, falcipain-3 and berghepain-2: implications for peptidase anti-malarial drug discovery; Biochem. J. (2006) 399, 47–57.
  4. Drahl, Carmen et. al. Protein Reactive Natural Products Angew. Chem. Int. Ed. (2005) 44, 5788. - a review of suicide inhibitors, including E-64.
  5. Chansuda W, Amy L P, et. al Epidemiology of drug-resistant malaria; The Lancets Infectious Diseases; 2,(4), 2002, p 209-218

Reviews of the Ugi reaction

  1. Wikipedia Great starting point with many reviews listed
  2. Domling and Ugi (2000) Multicomponent Reactions with Isocyanides

Mechanism of Ugi reaction

  1. Marcaccini & Torroba; Nature Protocols (2007) (Private Access)
  2. Demartino presentation (2003)
  3. Bu & Kjoniksen 2004 Biomacromolecules General scheme where isocyanide is added before acid.
  4. Bu & Kjoniksen 2005 European Polymer Journal General scheme where isocyanide is added before acid.
  5. A Plausible Mechanism- Ugi Reaction (ref: Keating and Armstrong 1996 although tetrahedral intermediate is not shown in their mechanism). General Ugi reaction mechanism .

Use of the Ugi reaction in Virtual Libraries

  1. Rarey & Lengauer 2007 Book


1. Private Access The Hydrophobic Effect 2. Relative Importance of the Hydrophobic Effect on the Solubility of Hydrophobes and Pharmaceuticals in H-bonded solvents. Journal of Pharmaceutical Sciences. 1998 (87), Iss. 8, pgs. 998-1014
2. Private Access Quantitative Solubility-Structure Relationships for some meta- and para- substitutued Benzoic Acids in p-doixane and in Tetrahydrofuran.

Acid-catalyzed Ring opening/polymerization of furans

  1. hydrolysis is one example - find refs
  2. Gonzalez 1992 Macromolecular Chemistry and Physics, Polymerization of furfuryl alcohol with TFA

Malaria Inhibition Assays

  1. PfENR UV assay (Perozzo 2002)>
  2. 2003 JBC Kuo Targeting Tuberculosis and Malaria through inhibition of enoyl reductase.

Reviews on the synthesis of diketopiperazines

  1. 2006 Chem. Rev. Doemling see p. 32 Ref 103 looks interesting
  2. 2005 Doemling
  3. 2003 Hulme Methods in Enzymology
  4. 1996 Ellman Chem. Rev. Solid Support DKP synthesis (see p. 571)
  5. Multicomponent Reaction J. Zhu, H. Beinayme (Wiley)

Examples of the synthesis of diketopiperazines with required substitution pattern

  1. 1998 Hulme Tet. Lett. Uses cyclohexenyl isocyanide and benzyl isocycanide but limited experimental data.
  2. 1995 Steele Solid Support strategy - does not use Ugi reaction

Relevant but not perfect for our Ugi reaction/cyclization

  1. Sollis 2005 J. Org. Chem. This one has the right substitution pattern and has lots of good info on cyclizing and characterizing DKPs but has an extra amide group
  2. 2004 Thomas Godet Titanium Catalysis in the Ugi Reaction of external image alpha.gif-Amino Acids with Aromatic Aldehydes - aromatic aldehydes are sluggish and can be accelerated with TiCl4
  3. Marcaccini 2001 Tetrahedron Letters (chloroacetic acid route) Wrong substitution pattern but an example of the synthesis of DKPs using UDC.
  4. 1996 Armstrong J. Am. Chem. Soc. Full description of the use of cyclohexenyl isocyanide as a convertible isonitrile.
  5. Hiromu Habashita et al. 2006 J Med. Chem A spirodiketopiperazine synthesis using an isonitrile resin through the Ugi reaction, sequential transformation and cyclative cleavage.
  6. Harriman 1997 Tet. Lett. Use of the morpholinoethyl isocyanide in an intramolecular Ugi reaction with good yields in methanol 48 hours.
  7. Bothwick 2005 J. Med. Chem. Contains NMR data of products, describes use of t-butyl and isopropyl isocyanides in a Ugi synthesis with slightly different reagents.
  8. Zhu,D; Chem, R;; An Efficient Procedure for the synthesis of Morpholino-2-one-3-carboxamide Derivatives in Good Diastereoselectivity by the Ugi Reaction (Private Access)

Imine formation

  1. Phenylacetaldehyde
  2. Buchanan and Dawson, Organic Magnetic Resonance, Vol 13 Iss 4 293-298 1980- NMR characterization of certain Imines.(Private Access)
  3. Li, Rerr Yu; Bei, Feng Li, Wang, Xin; (Chinese Journal of Organic Chemistry, Vol. 23 No. 9, 984-987) The article deals with the solid-phase reaction of furfurylamine and vanillin at room temperature. The product is characterized by proton NMR and other techniques including crystal structure analysis. (Private Access).

Imine Rates

  1. 2003 Moonkwon Lee; Jaebum Choo Gives a rate of a similar imine monitored by Raman spectroscopy which is very close to the rates we have been getting - about 0.01 /M*min in CDCl3 for acetophenone and aniline derivatives
  2. Jack Hine, Michael S. Cholod, and Walter K. Chess : (Journal of American Chemical Society Vol-95, Iss-13 pp 4270 - 4276) Kinetics of the formation of imines from acetone and primary amines. Evidence for internal acid-catalyzed dehydration of certain intermediate carbinolamines - about 0.1 /M*min in water for n-butylamine and acetone

Isocyanides NMR:
  1. Stephany et al.A 13C- NMR and IR Study of Isocyanides and Some of Their Complexes Organic Magnetic Resonance 1974 Vol 6 pp 45-47. (Private access)
  2. I. D. Kuntz, Jr., Paul von Ragué Schleyer, and A. Allerhand. J.; Long- Range N14-H1 Nuclear-Resonance Coupling in Isonitriles; I. D. J. Chem. Phys. 1961, 35, 1533-1534. (Private Access)

Furan Alkylation
  1. É. Ya. Lukevits, Chemistry of Heterocyclic Compounds; Vol. 22, Iss. 6 pp 678-679.
  2. Kosei Ohno and Minoru Machida Tet.Lett. Vol. 22, Iss. 45 pp 4487-4488; 1981 (Private Access)

  1. JCAMP-DX for NMR :DAVIES and LAMPEN Applied Spectroscopy , Vol 47, Iss 8 1093-1099, Aug 1993
  2. Removal of t-butoxycarbonyl protecting groups with trifluoroacetic acid. (Lundt, Johansen, Volund, Markussen) Int J Pept Protein Res. 1978 Nov;12(5):258-68
  3. General Isonitrile syntheses (Private Access)
  4. Microwave assisted Isonitrile synthesis J. Org Chem. 2005, 70, 2361-2363
  5. Synthesis of Cyclohexen-1-yl-isocyanide and N-Cylcohex-1-enyl-formamide Bioorganic & Medicinal Chemistry Volume 8, Issue 6 , June 2000, Pages 1343-1360
  6. Rapid deprotection of N-Boc amines by TFA combined with freebase generation using basic ion-exchange resins :Molecular Diversity, Volume 9, Number 4 / November, 2005
  7. NMR Chemical Shifts of Common Laboratory Solvents as Trace Impurities ; J. Org. Chem. 1997, 62, 7512-7515