Amino acid N-protected

Hromoethyl esters of amino acids. N-Protected amino acids are esterified by 2-bmmoelhanol in THF or CH2C12 with DCC. These esters are stable in moderately acidic or basic media. They are cleaved by conversion to the 2-iodoethyl ester by I inkclslein exchange with Nal followed by zinc reduction in DMF. On treatment... 

C-terminal peptide tiiioesters are used extensively in synthetic protein chemistry, especially for native chemical ligation (NCL) and other chemoselective reactions, which has inspired a search for robust synthetic strategies. Initially, peptide thioesters were mainly prepared using solid-phase peptide synthesis with amino acids N -protected with Boc (Boc-SPPS) [1-3], see Chapter 4. However, this technique requires specialized equipment for handling of hydrofluoric acid (HP) for release of the peptide from the resin, and it is therefore currently not used in many laboratories. Furthermore, the HP treatment is incompatible with many post-translational modiflcations such as glycosylations or phosphorylations [4]. Boc-SPPS is described thoroughly in Chapter 4. 

PhCH20COCl, Na2C03, H20,0°, 30 min, 72% yield. Alpha-omega diamines can be protected somewhat selectively with this reagent at a pH between 3.5 and 4.5, but the selectivity decreases as the chain length increases [H2N(CH2) NH2, n = 2, 71% mono n = l, 29% mono]. Hindered amino acids are protected in DMSO (DMAP, TEA, heat, 47-82% yield). These conditions also convert a carboxylic acid to the benzyl ester. ... 

WD Fuller, M Goodman, FR Naider, Y-F Zhu. Urethane-protected a-amino acid N-carboxy-anhydrides and peptide synthesis. Biopolymers (Pept Sci) 40, 183-205, 1996. 

Various N-alkylated derivatives of amino acids are natural products [e.g., H-D-(Me)Tyr-OH (D-surinamine) and H-(Me)Trp-OH (abrin) were found in cabbage tree bark1691] and many of them are used as enzyme inhibitors, receptor agonists and antagonists, building blocks for heterocyclic scaffolds in combinatorial chemistry, etc. In this section the preparation of N-alkyl amino acids in solution for their use in peptide synthesis is described. This implies that the synthetic procedures described in this section will ultimately result in V-alkyl amino acids appropriately protected for peptide synthesis. 

Peptide thioester 84 was prepared from 81 (0.3 g of resin). All amino acids were protected with N-terminal Boc groups. The side-chain protections were as follows Arg(Tos), Asp(OCy), Cys[Bzl(4-Me)], Glu(OCy), His(Tos), Lys[Z(2-Cl)], Ser(Bzl), and Thr(Bzl). Each synthesis cycle consisted of (1) a 25-min deprotection with 55% TFA/CH2C12 and (2) coupling with Boc amino acid (4 equiv) and BOP or HBTU (4 equiv) in the presence of DIPEA (6 equiv) in DMF for 1 h. All couplings were monitored by the... 

Deng and co-workers have also applied the cinchona derivatives to the kinetic resolution of protected a-amino acid N-carboxyanhydrides 51 [48]. A variety of alkyl and aryl-substituted amino acids may be prepared with high se-lectivities (krei=23-170, see Scheme 10). Hydrolysis of the starting material, in the presence of the product and catalyst, followed by extractive workup allows for recovery of ester, carboxylic acid, and catalyst. The catalyst may be recycled with little effect on selectivity (run 1, krei=114 run 2, krei=104). The reaction exhibits first-order dependence on methanol and catalyst and a kinetic isotope effect (A MeOH/ MeOD=l-3). The authors postulate that this is most consistent with a mechanism wherein rate-determining attack of alcohol is facilitated by (DHQD)2AQN acting as a general base. 5-Alkyl 1,3-dioxolanes 52 may also... 

After acidic acetal cleavage the u-alkylated amino acid is protected with N Boc in a fourth step and esterified in a fifth. 

Kinetic Resolution of N-Urethane-protected Amino Acid N-Carboxy Anhydrides... 

Adams, N. L. and Shick, J. M., Mycosporine-like amino acids provide protection against ultraviolet radiation in eggs of the green sea urchin Strongylocentrotus droebachiensis, Photochem. Photobiol., 64, 149, 1996. 

UNCA urethane-protected a-amino acid N-carboxy anhydride... 

OL, -Dehydroamino acids. N-Protected (Cbo and Boc) (3-hydroxy-a-amino acid esters (ethyl, benzyl) are converted into the corresponding a,p-dehydroamino acid derivatives by DAST and pyridine in CHiCl, at 0° (6.5-90% yield). The hydroxy group is probably converted into the —OSFiNlCiH,), derbative, which undergoes trans-e m -... 

Regarding the synthesis of AT -Fmoc-protected amino acid N-carboxyanhydrides (Leuchs anhydrides, amino acid-NCAs)t l as highly activated derivatives, see Section 3.4.4. 

Scheme 9 Reaction of a-Amino Acid iV-Carboxyanhydrides and Urethane-Protected a-Amino Acid N-Carboxyanhydrides with a Nucleophile ...

The zinc-promoted reaction of allylic bromides 262 with chiral TV-protected a-amino aldehydes 261 affords the anti diastereomer 263 with generally high selectivity (Table 10-29) [168]. The choice of protecting group is critical to the stereochemical outcome of the reaction. When the amino acids are protected by an N-Boc group, poor diastereoselectivity is observed. 

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