Solid-phase based synthesis of biologically promising triazolyl aminoacyl (peptidyl) penicillins

Scale-up synthesis of TAP7f, an antitumoral triazolyl peptidyl penicillin

“…In the optimized previously reported solid phase synthesis of TAP7f (1) , Wang resin-bound Fmoc-phenylalanine (1, Scheme 1) was used as the starting material. To replace this solid support, commercial enantiomerically pure L-phenylalanine was used.…”

“…Triazolyl peptidyl penicillins (TAPs) are novel hybrids compounds with promising antitumoral activity. (1,2) TAPs structures are constituted by a penicillanic core linked to a peptide portion via a triazole group. These previously reported structures were synthesized through a well stablished solid-phase methodology, that allowed to obtain a small library with good yields.…”

Molecular Diversity by Olefin Cross-Metathesis on Solid Support. Generation of Libraries of Biologically Promising β-Lactam Derivatives

“…The molecular hybridization strategy has proven to be helpful in many aspects related to drug discovery, such as overcoming drug-resistance problems or improving active transport mechanisms. In particular, β-lactam-based hybrids have recently acquired importance owing to the fact that many of them exhibit very promising biological activity [ 54 , 55 , 56 , 57 , 58 , 59 ]. In order to further increase diversity and also obtain biologically interesting β-lactam-based hybrids, metathesis conditions, previously developed for the synthesis of chalcones, were applied for the cleavage step ( Table 3 ) [ 60 ].…”

Diisopropylcarbodiimide

“…4 (B) Bradley and co-workers have reported microwave-mediated secondary amine couplings and the labelling of peptides with a variety of fluorophores and quenchers in presence of HOBt/DIC. (D) Shen and co-workers have found ytterbium triflate as an efficient catalyst for the addition of amines to carbodiimides to N,N′,N′′-trisubstituted guanidines with a wide scope of amines under solventfree conditions.…”

“…(A) Mata and co-workers have described a methodology for the preparation of triazolyl aminoacyl (peptidyl) penicillins utilising acylation of immobilized amino acid with propiolic acid and DIC. 4 (B) Bradley and co-workers have reported microwave-mediated secondary amine couplings and the labelling of peptides with a variety of fluorophores and quenchers in presence of HOBt/DIC. 5 (D) Shen and co-workers have found ytterbium triflate as an efficient catalyst for the addition of amines to carbodiimides to N,N′,N′′trisubstituted guanidines with a wide scope of amines under solventfree conditions.…”