Professor Ayman El-Faham received his B.Sc. and M.Sc. in Physical Organic Chemistry from the University of Alexandria, Egypt. In 1991 he received his Ph.D. in organic chemistry (peptide synthesis) through a joint project between the University of Alexandria and the University of Massachusetts. From 1992 to 1999, he worked on new coupling reagents at Professor Carpino's Lab. Following a position as Head of the Chemistry Department, Beirut Arab University (2000 to 2004), and as Direct Manager of both the NMR and Central Lab at Alexandria University (2004 to 2008). He received his D.Sc. in peptide chemistry in 2010. He worked at King Saud University, as a Professor of Organic Chemistry since 2008 and his research interests include synthesis of peptides, green chemistry, heterocycles, and biologically active targets molecules.
Fmoc amino acid fluorides have proven to be generally useful for peptide synthesis, even in the c... more Fmoc amino acid fluorides have proven to be generally useful for peptide synthesis, even in the case of hindered systems such as those incorporating adjacent Aib residues. In such cases, Fmoc-Aib-F has been shown to be more efficient than the corresponding acid chloride (Fig. 1) because the urethane-protected amino acid chloride is converted much more readily than the acid fluoride to the corresponding oxazolone. On the other hand Fmoc-amino acid fluorides appear to have reached their limits in attempted applications to very highly hindered substrates, e.g. the coupling of Fmoc-protected proteinogenic amino acids to MeAib substrates. The corresponding amino acid chlorides, although long disregarded due to deficiencies associated with available protocols, can, in fact, overcome these limitations. In the presence of bis(trimethylsilyl)-acetamide (BSA), urethaneprotected amino acid chlorides provide for a far more efficient process than the corresponding fluorides (Fig. 1). By switching to other forms of that are more compatible with the acid chloride functionality such as N-arenesulfonyl protectants for which the already high reactivity of the acid chloride unit is increased by inductive effects, it is possible to couple Aib to MeAib units within a few minutes. Indeed it is even possible to couple MeAib to MeAib, a reaction never achieved previously. Because of its facile removal the Pbf group was used as Thus, Pbf-MeAib-Cl (1 eq.) was coupled to (2 eq.) in toluene in the presence of DIEA (2 eq.) and BSA (1 eq.) within 2-3 h in a 70% yield. The structure of the resulting dipeptide (Pbf-MeAib-MeAib-OMe), purified by preparative HPLC, was confirmed by NMR analysis, mass spectrometry, and CHN analysis. Removal of the Pbf-group by means of 10% dimethylsulfide in trifluoroacetic acid (v/v) for 1 h at ambient temperature yielded the desired dipeptide, MeAib-MeAibOMe, in a yield of 87%.
ABSTRACT Full details are presented for use of the Bsmoc amino-protecting group for both solid ph... more ABSTRACT Full details are presented for use of the Bsmoc amino-protecting group for both solid phase and rapid continuous solution syntheses. Application to the latter methodology represents a significant improvement over the corresponding Fmoc-based method for rapid solution synthesis due to the opportunity to use water or saturated sodium chloride solution rather than an acidic phosphate buffer to remove all byproducts, with consequent cleaner phase separation and higher yields of the growing peptide. Comparison of the Bsmoc and Bspoc functions showed that the former, because of steric hindrance, does not suffer from the competitive or premature deblocking observed with the Bspoc system. Because of its incorporation of a styrene chromophore, resin loading of Bsmoc amino acids could be followed as has previously been shown for the Fmoc analogues. Applications of Bsmoc chemistry to peptide sequences incorporating the base sensitive Asp-Gly unit gave less contamination due to aminosuccinimide formation than comparable syntheses involving standard Fmoc chemistry because a weaker or less concentrated base could be used in the deblocking step. Experimental details are presented for building up peptides in solution via the continuous methodology. Deblockings involved the use of insoluble piperazino silica as well as the polyamine TAEA which simplified aqueous separation of the growing, but nonisolated peptide product, from excess acylating agent and other side products formed in the deblocking process. By the appropriate choice of base, one can act selectively at either site of a molecule which incorporates both β-elimination and Michael acceptor sites as protective units (Bsmoc vs Fm and Fmoc vs Bsm).
Advantageous Applications of Azabenzotriazole (Triazo1opyridine)-based Coupling Reagents to Solid... more Advantageous Applications of Azabenzotriazole (Triazo1opyridine)-based Coupling Reagents to Solid-phase Peptide Synthesis ... Louis A. Carpino,*a Ayman El-Faham,a Charles A. Minorb and Fernando Albericio* a Department of Chemistry, University of Massachusetts, ...
Journal of the American Chemical Society, May 1, 1995
... Yield of deblocked peptide, 48%; purity, 93% (HPLC). (26) Akaji, Kuriyama, and Kiso have made... more ... Yield of deblocked peptide, 48%; purity, 93% (HPLC). (26) Akaji, Kuriyama, and Kiso have made use of HOAt as additive in connection with the use of DCIH as a coupling reagent for hindered systems. See ref 13. (27) Carpino, L. A.; El-Faham, A. J. Org. Chem. 1994, 59, 695. ...
Fmoc amino acid fluorides have proven to be generally useful for peptide synthesis, even in the c... more Fmoc amino acid fluorides have proven to be generally useful for peptide synthesis, even in the case of hindered systems such as those incorporating adjacent Aib residues. In such cases, Fmoc-Aib-F has been shown to be more efficient than the corresponding acid chloride (Fig. 1) because the urethane-protected amino acid chloride is converted much more readily than the acid fluoride to the corresponding oxazolone. On the other hand Fmoc-amino acid fluorides appear to have reached their limits in attempted applications to very highly hindered substrates, e.g. the coupling of Fmoc-protected proteinogenic amino acids to MeAib substrates. The corresponding amino acid chlorides, although long disregarded due to deficiencies associated with available protocols, can, in fact, overcome these limitations. In the presence of bis(trimethylsilyl)-acetamide (BSA), urethaneprotected amino acid chlorides provide for a far more efficient process than the corresponding fluorides (Fig. 1). By switching to other forms of that are more compatible with the acid chloride functionality such as N-arenesulfonyl protectants for which the already high reactivity of the acid chloride unit is increased by inductive effects, it is possible to couple Aib to MeAib units within a few minutes. Indeed it is even possible to couple MeAib to MeAib, a reaction never achieved previously. Because of its facile removal the Pbf group was used as Thus, Pbf-MeAib-Cl (1 eq.) was coupled to (2 eq.) in toluene in the presence of DIEA (2 eq.) and BSA (1 eq.) within 2-3 h in a 70% yield. The structure of the resulting dipeptide (Pbf-MeAib-MeAib-OMe), purified by preparative HPLC, was confirmed by NMR analysis, mass spectrometry, and CHN analysis. Removal of the Pbf-group by means of 10% dimethylsulfide in trifluoroacetic acid (v/v) for 1 h at ambient temperature yielded the desired dipeptide, MeAib-MeAibOMe, in a yield of 87%.
ABSTRACT Full details are presented for use of the Bsmoc amino-protecting group for both solid ph... more ABSTRACT Full details are presented for use of the Bsmoc amino-protecting group for both solid phase and rapid continuous solution syntheses. Application to the latter methodology represents a significant improvement over the corresponding Fmoc-based method for rapid solution synthesis due to the opportunity to use water or saturated sodium chloride solution rather than an acidic phosphate buffer to remove all byproducts, with consequent cleaner phase separation and higher yields of the growing peptide. Comparison of the Bsmoc and Bspoc functions showed that the former, because of steric hindrance, does not suffer from the competitive or premature deblocking observed with the Bspoc system. Because of its incorporation of a styrene chromophore, resin loading of Bsmoc amino acids could be followed as has previously been shown for the Fmoc analogues. Applications of Bsmoc chemistry to peptide sequences incorporating the base sensitive Asp-Gly unit gave less contamination due to aminosuccinimide formation than comparable syntheses involving standard Fmoc chemistry because a weaker or less concentrated base could be used in the deblocking step. Experimental details are presented for building up peptides in solution via the continuous methodology. Deblockings involved the use of insoluble piperazino silica as well as the polyamine TAEA which simplified aqueous separation of the growing, but nonisolated peptide product, from excess acylating agent and other side products formed in the deblocking process. By the appropriate choice of base, one can act selectively at either site of a molecule which incorporates both β-elimination and Michael acceptor sites as protective units (Bsmoc vs Fm and Fmoc vs Bsm).
Advantageous Applications of Azabenzotriazole (Triazo1opyridine)-based Coupling Reagents to Solid... more Advantageous Applications of Azabenzotriazole (Triazo1opyridine)-based Coupling Reagents to Solid-phase Peptide Synthesis ... Louis A. Carpino,*a Ayman El-Faham,a Charles A. Minorb and Fernando Albericio* a Department of Chemistry, University of Massachusetts, ...
Journal of the American Chemical Society, May 1, 1995
... Yield of deblocked peptide, 48%; purity, 93% (HPLC). (26) Akaji, Kuriyama, and Kiso have made... more ... Yield of deblocked peptide, 48%; purity, 93% (HPLC). (26) Akaji, Kuriyama, and Kiso have made use of HOAt as additive in connection with the use of DCIH as a coupling reagent for hindered systems. See ref 13. (27) Carpino, L. A.; El-Faham, A. J. Org. Chem. 1994, 59, 695. ...
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