1. Dipeptidyl alpha-fluorovinyl Michael acceptors: synthesis and activity against cysteine proteases
Koen Steert, et al. Bioorg Med Chem Lett. 2007 Dec 1;17(23):6563-6. doi: 10.1016/j.bmcl.2007.09.075. Epub 2007 Oct 23.
The synthesis of novel dipeptidyl alpha-fluorovinyl sulfones using a Horner-Wadsworth-Emmons approach on N-Boc-l-phenylalaninal is described. Inhibitory assays against a Leishmania mexicana cysteine protease (CPB2.8DeltaCTE) revealed low biological activity. Relative rates of Michael additions of 2'-(phenethyl)thiol with vinyl sulfone and alpha-fluorovinyl sulfone were determined, and ab initio calculations on several Michael acceptor model structures were performed; both were in agreement with the biological testing results.
2. A concise synthesis of tubuphenylalanine and epi-tubuphenylalanine via a diastereoselective Mukaiyama aldol reaction of silyl ketene acetal
Yunjeong Park, Mikyung Sim, Tong-Shin Chang, Jae-Sang Ryu Org Biomol Chem. 2016 Jan 21;14(3):913-9. doi: 10.1039/c5ob02239h. Epub 2015 Nov 26.
We have developed a straightforward and auxiliary-free synthetic route towards tBu-tubuphenylalanine (tBu-Tup) and tBu-epi-tubuphenylalanine (tBu-epi-Tup), which are the key components of tubulysins and their analogs. A Lewis acid-mediated diastereoselective Mukaiyama aldol reaction using silyl ketene acetal and N-Boc-L-phenylalaninal provided γ-amino-β-hydroxyl-α-methyl esters, which were deoxygenated to γ-amino-α-methyl esters under Barton-McCombie deoxygenation conditions. Notably, the desired tBu-Tup and tBu-epi-Tup were obtained in good overall yields in four steps.
3. Synthesis and antibacterial activity of tert-butyl [1-benzyl-2[(4-aryl-2-thiazolyl)hydrazono]ethyl]carbamate derivatives
Gülhan Turan-Zitouni, et al. Arch Pharm (Weinheim). 2007 Jun;340(6):310-4. doi: 10.1002/ardp.200600200.
The increasing clinical importance of drug-resistant fungal and bacterial pathogens has lent additional urgency to microbiological research and new antibacterial compound development. For this purpose, new tert-butyl[1-benzyl-2[(4-aryl-2-thiazolyl)hydrazono]ethyl]carbamate derivatives were synthesized and evaluated for antibacterial activity. The reaction of Boc-L-phenylalaninal with thiosemicarbazide gave the thiosemicarbazone which furnished the title compounds by reaction with phenacyl bromides. The newly synthesized compounds were screened for antibacterial activity and toxicity. While microdilution broth susceptibility assay was used for the antibacterial activity evaluation of the compounds against the strains E. coli (NRRL B-3704), M. luteus (NRRL B-4375), B. cereus (NRRL B-3711), P. aeruginosa (NRRL B-23), and S. fecalis (NRRL B-14617), the Artemia salina 96-well assay was used to determine cytotoxicities of the compounds. Observations obtained from the bioassays showed that some of the compounds are highly active against E. coli, M. luteus, and B. cereus when compared with the control agent and showed low toxicity.
