T-BOC amino acids

Analytical Properties p-Cyclodextrin SP or RSP (cycloheptamylose-SP, -RSP) note that the modifying ligand has a stereogenic center useful for reverse phase separation of a variety of analytes, especially for enantiomers that have bulky substituents that are beta to the stereogenic center can be used for cyclic hydrocarbons and for t-boc amino acids Reference 13-28... 

Hirulog-8 has the formula H-(D-Phe)-Pro-Arg-Pro-(Gly)4-Asn-Gly-Asp-Phe-Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-OH. Hirulog-8 was synthesized by conventional solid-phase peptide synthesis employing an Applied Biosystems 430 A Peptide Synthesizer. This peptide was synthesized using BOC-L-Leucine-O-divinylbenzene resin. Additional t-BOC-amino acids (Peninsula Laboratories,... 

To obtain peptides with C-terminal free carboxylic acid The t-Boc-amino acid-PAM resin (with the first amino acid already attached) is used as the solid support. In this case the coupling of the second amino acid is a conventional acylation of an amino group on the resin with an activated t-Boc-amino acid do not forget to deprotect the amino acid on the resin before the coupling of the following amino acid derivative. Use 200 mg of t-Boc-amino acid-PAM resin. 

Deprotect t-Boc-amino acid-PAM-resin (after swelling 0.5-1 h in DCM) mix for... 

Shake base-washed MBHA-resin for 30 min with 2 eq of t-Boc-amino acid and 2 eq of dicyclohexyl carbodiimide (DCC). 

Protection of amino groups. Di-t.butyl dicarbonate called (Boc)20 (which is not made from the very unstable t.butyl chloroformate) is well known as the most popular reagent for the preparation of t.Boc protected amines, especially t.Boc-amino acids in peptide chemistry. 

As has been demonstrated in Section 3.1.2.4, complexation of amino groups offers a quite different concept for reversible protection. Making use of this principle, the coordination of chromium carbyne complexes with amino acids was described as a new amino protection. Similarly, bis(ethylene-diamine)cobalt(III) complexes of amino acids constitute a new interesting method for protection which recently was extended to the development of a new type of anchoring in solid-phase synthesis (Scheme 69). First, a t-BOC amino acid is condensed with the aquabis(ethylenediamine)cobalt(lII) complex of p-aminomethylbenzoic acid. The handle obtained in this way is then linked to aminomethyl polystyrene to give the anchored amino acid (69). Due to the sufficient stability of the complex toward... 

H Kuroda, S Kubo, N Chino, T Kimura, S Sakakibara. Unexpected racemization of pro line and hydroxyproline phenacyl ester during coupling reactions with Boc-amino acids. Int J Pept Prot Res 40, 114, 1992. 

Procedure for BOC-amino acids. A solution of the amino acid (10 mol) in a mixture of dioxane (20 ml), water (10 ml) and 1 m sodium hydroxide (10 ml) is stirred and cooled in an ice-water bath. Di-t-butyl pyrocarbonate (1) (2.4 g, 11 mmol) is added and stirring is continued at room temperature for 30 minutes. The solution is concentrated in vacuo to about 10-15 ml, cooled in an ice-water bath, covered with a layer of ethyl acetate (30 ml) and acidified with dilute aqueous potassium hydrogen sulphate solution to pH 2-3 (Congo red). The aqueous phase is extracted with ethyl acetate (2 x 15 ml). The ethyl acetate extracts are pooled, washed with water (2 x 30 ml), dried over anhydrous sodium sulphate and evaporated in vacuo. The residue is recrystallised with a suitable solvent (e.g. ethyl acetate-hexane). 

Deprotection. The BOC group is easily removed under quite mildly acidic conditions, a feature which underlines its value in selective deprotection in peptide synthesis. Typically, treatment at room temperature for 30-60 minutes with a 1 m solution of hydrogen chloride in acetic acid, or with neat trifluoroacetic acid, is used. It is of interest that after t.l.c. of BOC-amino acids, brief exposure of the plates to hydrogen chloride fumes enables the ninhydrin reaction to be used to detect the presence of the liberated free amino acids. 

Active BOC-amino acid esters. Steglich et al. originally used reagent 2 to prepare active esters 5 of BOC-amino acids (4). Actually 2 can also be used to prepare BOC-amino adds by way of 3. In fact the two reactions can be combined for a one-pot preparation of activated BOC-amino acid esters (5). Thus 2 on reaction with f-butanol is converted into the activated t-butyl carbonate 3. This compound in combination with 1 equiv. of tetramethylguanidine as base (6, 246) converts an... 

N-t-BMyloxycarbouyUumiu> acids. Ainino acids, in the form of their salts with bennylirimethylammonium hydroxide (Irilon B), react with (I) in DMSO or DMF within a few hours to give BOC-amino acids in 80-90% yield. 

BOC-amino acids can also be prepared, in somewhat lower yields, by the reaction of the benzyltrimethylammonium salts of amino acids with t-bulyl phenylcarbonate (2,1. 85) in the presence of 1 molar eq. of triazole-1,2,4. 

Peptidyl oxime resin was prepared in the usual manner starting from the resin-bound Boc amino acid. This peptidyl oxime resin was treated with HOPip to afford the corresponding protected peptide active ester. The active ester was converted into the protected peptide acid by reduction with zinc/AcOH.t l... 

In 1984, when the 430A was introduced, the only scale was 0.50 mmol which used 2 mmol Boc amino acid cartridges. In 1987, a 7-mL reaction vessel was created for a 0.10 mmol synthesis using Innmol of Boc amino acid. These cycles were called the small-scale rapid cyclesh l since the time was 20 minutes compared to 45 minutes for the standard cycles. Also in 1987, Fmoc cycles using HOBt active esters were released. In 1992, Boc cycles with 2-(l//-benzotriazol-l-yl)-l,l,3,3-tetramethyluronium hexafluorophosphate (HBTU) activation for the 430A which did not have a neutralization step after the TFA deprotection, was reported.t Neutralization of the TFA-salt of the resin-bound amino... 

Chemoselective (V-ethylation of Boc-amino acids can be accomplished without racemization via the corresponding dianions. Thus, (V-t-butoxycarbonylamino acid (35) was converted into dianion (36) by treatment with 2 equiv. of Bu Li, followed by the reaction with 1 equiv. of triethyloxonium tetrafluoro-borate to give (V-ethyl derivative (37) along with a trace of ethyl ester (38). On treatment with 2.2 equiv. of the triethyloxonium salt (36 R = Ph) gave (38 R = Ph) in 95% yield (Scheme 17). ... 

Some reactions can be driven to completion by removing the products physically from the reaction. Products that are out of solution may be protected from further reaction. An excellent example is found for the selective removal of the Boc (t-butyloxycarbonyl) group from N-Boc-amino acid t-butyl esters [37]. As shown in Figure 4.14, treatment of the L-serine derivative 18 with anhydrous HC1 in... 

The reagent is prepared1 by the reaction of carbonyl chlorofluoride2 with /-butanol. Like f-butyl azidoformate, the reagent reacts with amino acids to give t-butyloxy-carbonylamino acids (BOC-amino acids).1... 

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