Azido-Masked Amino Function

The azido group can be reduced to an amino function and hereby serve as masked amino group. It is of particular use if additional orthogonalities are needed. Azido is stable towards treatment with piperidine (Fmoc deprotection), Pd(0) (Alloc removal) and acidic treatmet (cleavage of Mtt, Trt or other acid sensitive groups). However, as it is a pseudohalogenide, care has to be taken during coupling steps, as HATU will cause high racemization. This can be avoided using collidine or other non-nucleophilic bases instead of DIPEA.

Certainly 2-amino-3-azidobutanoic acid can be used for any type of click conjugation with any available alkynyl residue forming Diels-Alder conjugates of peptides or any other organic molecule.

Chiral α,β-diamines and diamino acids have become an increasing targeted functional motif in organic synthesis owing to their ubiquity in natural products and medicinal agents. For example, it is found in biotin, penicillins, and antiinfluenza neuraminidase inhibitor Tamiflu. Chiral vicinal diamines and their metal complexes have been employed in stereoselective organic synthesis, in particular, as chiral auxiliaries and ligands in catalytic asymmetric synthesis.

References:

• α,β-Diamino Acids: Biological Significance and Synthetic Approaches; Alma Viso, Roberto Fernández de la Pradilla, Ana García, and Aida Flores; Chemical Reviews 2005; 105(8): 3167-3196. DOI: 10.1021/cr0406561.
• Update 1 of: α,β -Diamino Acids: Biological Significance and Synthetic Approaches; Alma Viso, Roberto Fernández de la Pradilla, Mariola Tortosa, Ana García, and Aida Flores; Chem. Rev. 2011; 111: PR1–PR42. DOI 10.1021/cr100127y.
• Orthogonally Protected Cyclo-ß-tertapeptides as Solid-Supported Scaffolds for the Synthesis of Glycoclusters; Pasi Virta, Marika Karskela, Harri Lönnberg; J.Org.Chem 2006; 71: 1989-1999.
• Stereocontrolled Route to Vicinal Diamines by [3.3] Sigmatropic Rearrangement of Allyl Cyanate: Asymmetric Synthesis of anti-(2R,3R)-and syn-(2R,3S)-2,3-Diaminobutanoic Acids; Yoshiyasu Ichikawa, Haruka Egawa, Takashi Ito, Minoru Isobe, Keiji Nakano, and Hiyoshizo Kotsuki; Org.Lett. 2006; 8(25): 5737-5740.
• Efficient Synthesis of orthogonally protected anti-2,3-diamino acids; Stefania Capone, Annalisa Guaregna, Giovanni Palumbo, Silvana Pedatella; Tetrahedron 2005; 61: 6575-6579.