Didemnin antibiotics

Magnesium or lithium enolates of thiol carboxylic esters can be acylated with suitable reagents (c/ Volume 2, Part 1). Highly functionalized new derivatives are obtained. The example shown in equation (35)33,102 J5 closely related to the C-acylation of malonyl-CoA with acetyl-CoA, which plays an important role in the biosynthesis of polypeptides and fatty acids. (S)-4-Hydroxy-5-methyl-3-oxo-hexanoyl-L-leucine esters (41), 2-demethyl analogs of the Hip-Leu moiety of didemnin antibiotics, can be prepared via the 3-keto thiol carboxylic esters (40 equation 36). ° ... 

The performance of HSCCC-ESI-MS was evaluated by analyzing erythromycins and didemnins [10]. Because erythromycins (macrolide antibiotics) show weak UV absorbance and cannot be detected easily with a conventional UV detector, mass spectrometric detection is a very useful technique for analysis of these antibiotics. A mixture of erythromycin A (Er-A,... 

Although historically most useful antibiotics have come from spore forming microorganisms, marine organisms have yielded the candidate antitumor peptide didemnin B [77327-50-0] (2) and cytostatic peptides such as the patellamides (3). Many of the marine peptides have little or no antimicrobial activity. Antibacterial peptides called magainins are found in frog skin (4) and antibacterial proteins called defensins are found in mammalian white blood cells (5). The commercially important insecticidal proteins from Bacillus thuringensis (6) are not discussed herein nor are the numerous peptide siderophores (7,8), which, except for the albomycins (9), are usually not antimicrobial. 

The performance of HSCCC-ESI-MS was evaluated by analyzing erythromycins and didemnins. ° Because erythromycins (macrolide antibiotics) show weak UV absorbance and cannot be detected easily with a conventional UV detector, mass spectrometric detection is a very usefiil technique for analysis of these antibiotics. A mixture of erythromycin A (Er-A, MW 733), erythromycin estolate (Er-E, MW 789), and erythromycin ethyl succinate (Er-S, MW 789) was analyzed using HSCCC-ESI-MS with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (4 7 4 3). TIC showed, clearly, four peaks corresponding to Er-A, Er-E, Er-S, and an unknown substance. The mass spectra of Er-E and Er-S gave [M -f H]+ at miz 862 and 789 and [M - - H - H2O] at mIz 844 and 772, respectively. In the mass spectmm of Er-A, [M -I- H - H20] was observed at miz 761 however, no [M + H] was given. The mass spectrum of the unknown peak indicated that it consists of two components with molecular weights of 843 and 772, which correspond to dehydrated Er-S and Er-E, respectively. 

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