Application of the Lossen rearrangement to the synthesis of N-urethane protected a-peptidyl ureas and ureidopeptides is reported. The carbodiimide mediated rearrangement of N-Boc/Z/Fmoc protected a-amino/peptide hydroxamic acids into isocyanates and coupling of the latter with the amino acid esters/peptide esters have been accomplished in a single-pot to obtain good yields of urea products. Synthesis of the ureidoalanine derivatives via the hydroxamate derivatives of N-protected aspartic acid has also been carried out using the same procedure.

Synthetically useful N-Fmoc amino-alkyl isothiocyanates have been described, starting from protected amino acids. These compounds have been synthesized in excellent yields by thiocarbonylation of the monoprotected 1,2-diamines with CS2/TEA/p-TsCl, isolated as stable solids, and completely characterized. The procedure has been extended to the synthesis of amino alkyl isothiocyanates from Boc- and Z-protected amino acids as well. The utility of these isothiocyanates for peptidomimetics synthesis has been demonstrated by employing them in the preparation of a series of dithioureidopeptide esters. Boc-Gly-OH and Boc-Phe-OH derived isothiocyanates 9a and 9c have been obtained as single crystals and their structures solved through X-ray diffraction. They belong to the orthorhombic crystal system, and have a single molecule in the asymmetric unit (Z' = 1). 9a crystallizes in the centrosymmetric space group Pbca, while 9c crystallizes in the noncentrosymmetric space group P2(1)2(1)2(1).

This review provides a broad perspective of the uses of amino acid fluorides in the synthesis of peptides and a wide range of other molecules including peptidomimetics, heterocycles and biologically active molecules.

A series of three 5,5′-substituted hydantoin derivatives (1−3) were synthesized, and their crystal structures were solved using single-crystal synchrotron/powder-crystal X-ray diffraction data with a detailed analysis of Hirshfeld surfaces and fingerprint plots facilitating a comparison of intermolecular interactions in building different supramolecular architectures. A comparison of supramolecular assembly in the compounds with that in similar 5,5′-substituted hydantoins in the Cambridge Structural Database (CSD) has been presented. The crystal packing in compounds 1−3 containing complementary hydrogen bonding groups, i.e. the amino NH donors and carbonyl O acceptors, exhibits three types of supramolecular synthons. In the dipropyl substituted hydantoin (1), intermolecular N−H···O hydrogen bonds with only one carbonyl O atom acting as a double acceptor generate a one-dimensional C1 1(4)C1 1(4)[R2 2(8)] network propagating along the [100] direction, while in 3, a 5-spiro fused hydantoin, the cyclic R2 2(8) motifs self-organize through pairs of N−H···O hydrogen bonds to form a C2 2(9)[R2 2(8)][R2 2(8)] framework running along the [1−10] direction. The molecular assembly in 2, with a dibutyl substitution at the hydantoin C-5 position, produces R4 4(17) synthons, which are edge-fused to form two-dimensional molecular sheets in the (100) plane. The formation of a supramolecular architecture built with an R4 4(17) synthon is unprecedented among the substituted hydantoin structures in the CSD.

A novel class of optically active N-Fmoc-protected amino isonitriles has been described for the first time. Conversion of the carboxyl group of Fmoc-beta-amino acids into an isocyano group has resulted in a new class of N-urethane-protected amino isonitriles. All the isonitriles have been isolated as stable solids, purified, and completely characterized. A synthetic application of the obtained isonitriles has also been demonstrated through the synthesis of 1-substituted tetrazole analogues of amino acids via a 2 + 3 cycloaddition with trimethylsilyl azide.