N protected derivatives

Early syntheses of haloindoles involved direct reactions of indoles with chlorine, bromine, or iodine. In some cases, this approach was reasonably successful, but the instability of the resulting 3-haloindoles made product isolation and further chemistry difficult. For example, although attempted preparations of 3-chloro-, 3-bromo-, and 3-iodoindole were described in the early 1900 s [2], only recently have practical syntheses of these compounds and their N-protected derivatives become available. For example, 3-bromoindole (2) can be prepared in... 

Compounds 29, 34, 39, and 40 constitute chiral synthons suitable for use in stereospecific aninocyclitol synthesis. Thus, 40 or other, appropriately N protected derivatives of 39 may be employed for stereospecific substitution at OH-6 alternatively, after temporary protection of OH-6 followed by removal of the acetal, the molecule should be amenable to manipulation at OH-4. In 9 and 4, the two unequal nitrogenous functions may be reduced stepwise to amino groups, thus offering possibilities for stereospecific introduction of an N-substituent at either position. In order to demonstrate that such a strategy is feasible, reaction sequences leading to the enantiomers of mono-N-methyl-2-deoxystreptamine were performed, as illustrated in Figure 5. 

Synthesis of 2-Substituted Pyrroles via a-LiTHiATiON of N-Protected Derivatives... 

Synthesis of 3(5)-Substituted 1,2,4-Triazoles via a-LiTHiATioN of N -Protected Derivatives... 

The synthesis of jS-hydoxy-a-amino acids is important since these compounds are incorporated into the backbone of a wide range of antibiotics and cyclopeptides such as vancomycins. These highly functional compounds are also subject to dynamic kinetic resolution (DKR) processes, as the stereocenter already present in the substrate epimerizes under the reaction conditions and hence total conversions into single enantiomers are possible. These transformations can be iy -selective ° for N-protected derivatives as shown in Figure 1.27 when using a mthenium-BlNAP catalyzed system and anfi-selective when the jS-keto-a-amino acid hydrochloride salts are reduced by the iridium-MeOBlPHEP catalyst as shown in Figure 1.28. One drawback is that both these reductions use 100 atm hydrogen pressure. 

A-Trialkylsilyl- and TV-trialkylstannylazoles are useful N-protected derivatives for a number of transformations, and suitably volatile for GLC analysis. The groups are thermally stable, but susceptible to hydrolytic and analogous displacements, with the stannyl compounds less readily hydrolyzed than the silyl species. 

The main problem a peptide chemist has to tackle with CMetrasubstituted a-amino acids is their rather poor reactivity in peptide-bond formation due to steric hindrance at the a-carbon. In addition, during the activation process of the carboxylic function of peptides and urethane or amide N-protected derivatives, an intramolecular reaction leading to the oxazoI -5 (4 //) -on e heterocyclic skeleton is greatly favored by the gem-dialkyl effect (Scheme... 

Zambon succeeded in converting the terminal CH2OH, in an N-protected derivative of XVIII, into CH2 F confirming the viability of the option [see Chapter 7 for both the Zambon synthesis of Florfenicol (Scheme 9) and further ramifications of the project]. 

An additional alternative is the selective preparation of N -protected diamino acids and their use for the synthesis of the asymmetrically N ,N -protected derivatives. One approach is based on the use of the a-protected Tfa-Lys-OH (3) and Tfa-Om-OH derivatives, which are accessible in good yields by direct reaction of lysine and ornithine with trifluoroacetic anhydride in trifluoroacetic acid.f l... 

The A -Boc-protected diamino acids are prepared via the copper(II) complexes of lysine or ornithine,b l or by using suitable N -protected derivatives obtained by the benzylidene route under conventional Schotten-Baumann conditionsJ l Since previous reports differ in yields and are not completely reproducible, the procedures have been optimizedJ l Thereby, the chelating resin Chelex 100 can efficiently be used for decomposition of the Cu[Lys(Boc)]2 complex. However, as this resin is expensive, an alternative procedure has been proposed for large-scale synthesis that is based on the use of the inexpensive quinolin-8-ol to quantitatively remove the copper(II) ions.P l The resulting H-Lys(Boc)-OH intermediate is then converted into the desired N -protected form by the classical procedures reported in Section 2.1.1. For cleavage of the A -Boc protection by various acidic reaction conditions, see Section 2.1.1.1.3.1.3. 

A 37% aq soln of CH2O (19.3 mL, 260 mmol) was added to H-Ser-OH or H-Thr-OH (103 mmol) in aq 2.5 M Na2C03 (32 mL) at rt. The clear soln was left standing overnight at 4°C, after which the pH was 7.8. This soln was used directly for aminoacylation with Fmoc-protected amino acid fluorides or UNCAs to produce the dipeptide synthons, - or with Z-Cl and (Boc)20 to produce the related N -protected derivatives. ... 

S-, N-Protective derivatives. The reagent reacts under mild acid catalysis with primary and secondary alcohols, and with phenols, to form tetrahydropyranyl ethers, which are stable to bases, to RMgX, to L1AIH4, to acetic anhydride in pyridine, and to oxidation. When synthetic operations at another site in the molecule have... 

F. (2004) Synthesis of the enantiomers and N-protected derivatives of 3-amino-3-(4-cyanophenyl)propanoic acid. Tetrahedron Asymmetry, 15, 1893-1897. 

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