N-Protective groups, removal

Carbo-9-fluorenylmethoxyl as N-protective group Removal by / -elimination... 

Piperidinoxy carbonyl as N-protective group Removal of the protective group... 

In each step of the usual C-to-N peptide synthesis the N-protecting group of the newly coupled amino acid must be selectively removed under conditions that leave all side-chain pro-teaing groups of the peptide intact. The most common protecting groups of side-chains (p. 229) are all stable towards 50% trifluoroacetic acid in dichloromethane, and this reagent is most commonly used for N -deprotection. Only /ert-butyl esters and carbamates ( = Boc) are solvolyzed in this mixture. 

APA may be either obtained directly from special Penicillium strains or by hydrolysis of penicillin Q with the aid of amidase enzymes. A major problem in the synthesis of different amides from 6-APA is the acid- and base-sensitivity of its -lactam ring which is usually very unstable outside of the pH range from 3 to 6. One synthesis of ampidllin applies the condensation of 6-APA with a mixed anhydride of N-protected phenylglydne. Catalytic hydrogenation removes the N-protecting group. Yields are low (2 30%) (without scheme). 

Tandem cyclization/3-substitution can be achieved starting with o-(trifluoro-acetamido)phenylacetylenes. Cyclization and coupling with cycloalkenyl trif-lates can be done with Pd(PPh3)4 as the catalyst[9]. The Pd presumably cycles between the (0) and (II) oxidation levels by oxidative addition with the triflate and the reductive elimination which completes the 3-alkenylation. The N-protecting group is removed by solvolysis under the reaction conditions, 3-Aryl groups can also be introduced using aryl iodides[9]. 

N-deprotection Removal of N-protecting groups, nonpeptidomimetics Nonpeptide analogues, usually small molecules, nonpolar Hydrophobic molecules that are poorly soluble in water, oligopeptide A few amino acids joined by peptide bonds. 

Benzyl -o-xylopyranoside was converted into the alcohol 54 (a somewhat capricious isopropylidenation) [39] and a Mitsunobu inversion with N-hydroxyphthalimide, followed by protecting group removal, gave the hydro-xylamine 55. Transfer-hydrogenation (ammonium formate and palladium-on-charcoal in refluxing methanol) [40] then gave, on a small scale and in almost a quantitative yield, the enantiomer of the desired tetrahydro-l,2-oxazine 52. We have never been able to repeat this result since Figure 4 shows the NMR spectra acquired at the time [41]. 

A -Benzyl groups on pyrimidinones and quinazolinones are removable by hydrogenolysis, although it is now more common to use a PMB substituent that can be removed with either TFA or CAN. Other N-protecting groups to be commonly used include benzyloxymethyl (BOM), removable by hydrogenation, ferZ-butoxycarbonyl (BOC), removable by anhydrous acid, and pivaloyloxymethyl (POM), which is removable by methanolic ammonia at room temperature. Alkenyl pyrimidinones have been employed in 1,3-dipolar cycloaddition reactions to prepare heterocyclic nucleotides. 

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