N-protecting groups for

Scheme 62 Dimedone as a N-Protecting Group for Amino Acidsl " ...

A more convenient N-protecting group for aminoalkyl carbamates, diphenyl-methylidene, [69] was explored by Boie and Hoppe [Eq. (27)] [70]. Alkyl carbamate 89, derived from (R)-2-amino-1 -butanol was smoothly deprotonated by... 

This procedure facilitates the use of a methyl group as an N-protectIng group for pyrazoles. 

Primary and secondary amines are susceptible to oxidation and replacement reactions involving the N—H bonds. Within the development of peptide synthesis numerous protective groups for N—H bonds have been found (M, Bodanszky, 1976 L.A. Carpino, 1973), and we shall discuss five of the more general methods used involving the reversible formation of... 

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. 

Carbamates can be used as protective groups for ammo acids to minimize race-mization in peptide synthesis. Raccmi/ation occurs during the base-catalyzed coupling reaction of an W-protected, catboxyl-uc ivated amino acid, and takes place in the intermediate oxazolone that foro S readily from an N-acyl protected amino... 

A tert-butyl ester serves as an efficient organyl-stabilizing group for a lithiated aziridine when the N-protecting group is a chelating moiety. Deprotonation/elec-... 

The development and use in peptide synthesis of the 1-adamantyloxymethyl protecting group for N -histidine 28 was reported <9 CS(P1)2139>. A procedure for the regiospecific alkylation of histidine and histamine at N-l(t) via the corresponding tetrahydro oximidazo[l,5-c]pyrimidines 29 was also developed <96T5363>. 

HydTOX5 proline-derived polyesters are usually readily soluble in a variety of organic solvents (benzene, toluene, chloroform, dichloro-methane, carbon tetrachloride, tetrahydrofuran, dimethylformamide, etc.) As expected, the solubility in hydrophobic solvents increased with increasing chain length of the N protecting group, while the solubility in polar solvents decreased. For example, poly(N-hexanoyl-hydroxyproline ester) is slightly soluble in ether but easily soluble in acetonitrile, while poly(N-palmitoylhydroxyproline ester) is readily soluble in ether but virtually insoluble in acetonitrile. 

Phenylthioethyl has been used as a protecting group for N-3 of thymidine during manipulation of the sugar. It was removed via oxidation to the sulfone <06SL845>. 

The suitability of the Aloe group for the construction of lipidated peptides is emphasized by the synthesis of the maleimidocaproyl-modified, S-palmi-toylated and farnesylated heptapeptide 16 which corresponds to the N-Ras C-terminus (Scheme 10).1211 In contrast to classical urethane-type protecting groups, the Aloe group can be removed in the presence of additional functional groups and under neutral conditions. It is therefore a very convenient protecting group for the synthesis of very hydro-phobic lipid-modified peptides, which are not soluble in the aqueous media required for enzyme catalyzed transformations. 

Scheme 11.3 Using a C2-protecting group for arming/disarming of an n-pentenyl glycoside for oxonium ion formation.

Y Okada, J Wang, T Yamamoto, Y Mu, T Yokoi. Amino acids and peptides. Part 45. Development of a new N-protecting group of histidine, NK-( -adamantyloxymethyl)-histidine, and its evaluation for peptide synthesis. J Chem Soc Perkin Trans 1 2139. 1996. 

T lohnson, RC Sheppard. A new t-butyl-based acid-labile protecting group for the guanidine function of Na-11 uorcnyI mcthyoxycarbonyl -argi n i nc. (Btb) J Chem Soc Chem Commun 1605, 1990. 

Notably, the aminoalkylation reaction did not occur with iV-protected indoles revealing the crucial role of the free N-H group for the activation by the phosphoric acid. This prompted the authors to postulate the transition state model depicted in Fig. 6. 

Azido aldehydes and a-protected amino aldehydes have been used to incorporate the nitrogen in the aldolase-catalyzed reaction (for an extensive review on aldolase-mediated synthesis of iminocyclitols, see [28] and references therein). The steri-cally unhindered azido and N-formylamino aldehydes display a marked kinetic advantage over analogs having larger and/or poor water-soluble N-protecting groups [29]. 

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