Hexafluoroacetone as Protecting and Activating Reagent: New Routes to Amino, Hydroxy, and Mercapto Acids and Their Application for Peptide and Glyco- and Depsipeptide Modification

Spengler,Jan;Bottcher,Christoph;Albericio,Fernando;Burger,Klaus

Chem. Rev.
Vol.106(11) 2006 pp.4728–4746
DOI: 10.1021/cr0509962
http://pubs.acs.org/doi/abs/10.1021/cr0509962

Table of Contents

1. Introduction: Bidentate Protecting/Activating Reagents for ?-Functionalized Carboxylic Acids
2. Reaction of Hexafluoroacetone with ?-Functionalized Carboxylic Acids
   2.1. Protection/Activation of ?-Amino, ?-Hydroxy, and ?-Mercapto Acids
   2.2. Some Properties of HFA-Protected Compounds
   2.3. Side Reactions: Perfluoromethylated Pseudoproline from Glycine
   2.4. Application of HFA in ?-Keto Acid Chemistry
   2.5. Reaction of HFA with Peptides
3. Derivatization/Deprotection of HFA-Amino, HFA-Hydroxy, and HFA-Mercapto Acids
   3.1. Derivatization/Deprotection in Solution
   3.2. Derivatization/Deprotection on Solid Phase
   3.3. Symmetric and Unsymmetric Diketopiperazines
4. Site-Selective Derivatization of ?-Functionalized Dicarboxylic Acids
   4.1. Activation of the ?-Carboxy Group
   4.2. ?-Esters
   4.3. ?-Amides and ?-Peptides
   4.4. Acylation of Glycosylamines
   4.5. Homologation via Arndt?Eistert Reaction of Diazoketones
5. ?-Isocyanates from ?-Functionalized ?,?-Dicarboxylic Acids
   5.1. Synthesis of ?-Isocyanates
   5.2. ?-Functionalized ?-Amino Acids: Isoserine, ?-Methylisoserine, Isocysteine, N?-Methyl Diamino Propionic Acid, and Homologues
   5.3. ?-Functionalized ?-Amino Acids as Multifunctional Scaffolds and Urea-Linked Glycoconjugates
6. ?-Diazoketones from ?-Functionalized Dicarboxylic Acids
   6.1. Heterocyclic Amino Acids via Cycloadditions
   6.2. Acid-Catalyzed Decomposition of the Diazo Compounds: HON, 4-Oxoornithine, Hantzsch Reaction
   6.3. Intramolecular Rhodium-Catalyzed NH Insertion: New Routes to Prolines, Pipecolic Acids, and Bulgecinine
7. Further Site-Selective Transformations of Side-Chain Carboxy Groups
   7.1. Rosenmund Reduction: Armentomycin and Fluoro Analogues
   7.2. Friedel?Crafts Acylation: Aroylalanines, 4,4-Difluoroglutamic Acid
   7.3. Stille Reaction: Aroylalanines and Pipecolic Acids
   7.4. ?-Trifluoromethyl-Substituted Compounds via SF4 Fluorination
   7.5. Miscellaneous: Bromoalanine Analogues, (S)-?-Oxoornithine, Dihydroorotic Acid
8. Transformations of HFA-Amino Acids Including the NH Function
   8.1. N-Halomethylation of HFA-Protected Amino Acids
   8.2. One-Pot Synthesis of N?-Methyl Amino Acids
   8.3. ?-Carboxy-N?-Methylamino Acids
   8.4. N?-Ethylamino Acids
 
   8.5. N-Phosphinoylmethylamino Acids
   8.6. Conformationally Restricted Chimeric Amino Acids
   8.7. Asymmetric Pictet?Spengler Reaction: Tic Chimeras
9. Further Site-Selective Transformations
   9.1. O-Glycosylation of HFA-Protected Ser, Thr, Tyr, and 4-OH?Pro]
   9.2. C-Glycosylated Amino Acids
   9.3. Phosphonyl Sarcosine Derivatives
10. Outlook
11. Abbreviations
12. Acknowledgments
13. References

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Amino-Acid Protecting Groups

Isidro-Llobet,Albert;Alvarez,Mercedes;Albericio,Fernando

Chem. Rev.
Vol.109(6) 2009 pp.2455–2504
DOI: 10.1021/cr800323s
http://pubs.acs.org/doi/abs/10.1021/cr800323s

Table of Contents

1. Introduction
2. a-Amino
   2.1. General
   2.2. Introduction of the Protecting Groups
   2.3. Removal
   2.3.1. Protecting Groups Removed by Acid (Table 1)
   2.3.2. Protecting Groups Removed by Base (Table 2)
   2.3.3. Other Protecting Groups (Table 3)
3. Lysine (Lys), Ornithine (Orn), Diaminopropionic Acid (Dap), and Diaminobutyric Acid (Dab)
   3.1. General
   3.2. Introduction of the Protecting Groups
   3.3. Removal
   3.3.1. Protecting Groups Removed by Acid (Table 5)
   3.3.2. Protecting Groups Removed by Base (Table 6)
   3.3.3. Other Protecting Groups (Table 7)
4. a-Carboxylic Acid
   4.1. General
   4.2. Introduction of the Protecting Groups(174)
   4.3. Removal
   4.3.1. Protecting Groups Removed by Acid (Table
   4.3.2. Protecting Groups Removed by Base (Table 9)
   4.3.3. Other Protecting Groups (Table 10)
5. Aspartic (Asp) and Glutamic (Glu) Acids
   5.1. General
   5.2. Introduction of the Protecting Groups
   5.3. Removal
   5.3.1. Protecting Groups Removed by Acid (Table 11)
   5.3.2. Protecting Groups Removed by Base (Table 12)
   5.3.3. Other Protecting Groups (Table 13)
6. Amide Backbone
   6.1. General
   6.2. Introduction of the Protecting Groups
   6.3. Removal
   6.3.1. Protecting Groups Removed by Acid (Table 14)
   6.3.2. Other Protecting Groups (Table 15)
7. Asparagine (Asn) and Glutamine (Gln)
   7.1. General
   7.2. Introduction of the Protecting Groups
   7.3. Removal
   7.3.1. Protecting Groups Removed by Acid (Table 16)
8. Arginine (Arg)
   8.1. General
   8.2. Introduction of the Protecting Groups
   8.3. Removal
   8.3.1. Protecting Groups Removed by Acid (Table 17)
   8.3.2. Protecting Groups Removed by Base (Table 18)
   8.3.3. Other Protecting Groups (Table 19)
9. Cysteine (Cys)
   9.1. General
   9.2. Introduction of the Protecting Groups
   9.3. Removal
   9.3.1. Protecting Groups Removed by Acid (Table 20)
   9.3.2. Protecting Groups Removed by Base (Table 21)
   9.3.3. Other Protecting Groups (Table 22)
10. Methionine (Met)
   10.1. General
   10.2. Introduction of the Protecting Groups
   10.3. Removal: Sulfoxide Reduction
         Met des-tert-butylation
11. Histidine (His)
   11.1. General
   11.2. Introduction of the Protecting Groups(394)
   11.3. Removal
   11.3.1. Protecting Groups Removed by Acid (Table 23)
   11.3.2. Protecting Group Removed by Base (Table 24)
           N?-9-Fluorenylmethoxycarbonyl (Fmoc)(405)
           N?-2,6-Dimethoxybenzoyl (Dmbz)(406)
   11.3.3. Other Protecting Groups (Table 25)
           N?-2,4-Dinitrophenyl (Dnp)(407)
12. Serine (Ser), Threonine (Thr), and Hydroxyproline (Hyp)
   12.1. General
   12.2. Introduction of the Protecting Groups
   12.3. Removal
   12.3.1. Protecting Groups Removed by Acid (Table 26)
   12.3.2. Other Protecting Groups (Table 27)
13. Tyrosine (Tyr)
   13.1. General
   13.2. Introduction of the Protecting Groups
   13.3. Removal
   13.3.1. Protecting Groups Removed by Acid (Table 28)
   13.3.2. Other Protecting Groups (Table 29)
14. Tryptophan (Trp)
   14.1. General
   14.2. Introduction of the Protecting Groups
   14.3. Removal
   14.3.1. Protecting Groups Removed by Acid (Table 30)
   14.3.2. Protecting Groups Removed by Base
   14.3.3. Other Protecting Groups (Table 31)
15. Abbreviations
16. Acknowledgments
17. References

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