BOC-Amino Acids

Introduction

In nature, there are 20 kinds of natural amino acids. In recent years, many efforts have been made in the modification of amino acids, and many non-natural amino acids have been created. Non-natural amino acids play an important role in the field of proteins and peptides. BOC-amino acid is a common and typical non-natural amino acid. There are many ways to synthesize BOC-amino acids. For example, tert-butyl oxycarbonyl (BOC) amino acids are commonly used as intermediates in the synthesis of polypeptides. The preparation method is the reaction of 1,1,3,3-tetramethylguanidinium salts of some amino acids with tert-butyloxycarbonyl azide in 4-dimethylaminopyridine as the solvent. Also, BOC group is used as a protecting group for amines in organic synthesis (Fig. 1).

Common amine protection and deprotection methods Fig. 1 Common amine protection and deprotection methods

Applications

Proteins: The programmed incorporation of unnatural amino acids with new functional side chains will provide a powerful approach for protein or even organism engineering with novel functionalities and capabilities. The recent successful development of technologies for incorporating unnatural amino acids into proteins in vivo has generated an additional strategy for modulating protein function. Unnatural amino acids can now be incorporated into a specific site of protein during translation by employing the amber codon as the genetic codon for unnatural amino acids. The incorporation of unnatural amino acids into proteins by site-specific mutagenesis provides a valuable new methodology for the generation of novel proteins that possess unique structural and functional features.

Synthesis of t-Boc-Met-CPT(1a) and the intermediate t-Bot-Gly-CPT(int 1) Fig. 2 Synthesis of t-Boc-Met-CPT(1a) and the intermediate t-Bot-Gly-CPT(int 1)

Peptide synthesis: The segment condensation method is an important technique in the synthesis of large peptides. Two different approaches are available, the minimum and the maximum protection strategies. Theoretically, the latter strategy is advantageous in t e r m of minimizing side reactions since all functional groups are protected during elongation reactions. If those protected segments can be assembled with Boc-amino acids, which are commonly used for the ordinary solid-phase method, the procedure should be more practical. Chemical peptide syntheses consume extremely large quantities of organic solvent due to the multiple solvent-based condensation steps,which damage the environment. Water-based peptide synthesis remained unexplored for a long period, because of the most common peptide building blocks, t-butyloxycarbonyl (BOC)- and 9-fluorenylmethoxycarbonyl (Fmoc)-amino acids , are sparingly soluble in water. aqueous peptide synthesis methods that utilize water-dispersible Boc- and Fmoc-amino acids nanoparticles. This technology uses suspended nanoparticle reactants for the coupling reaction to overcome the solubility problem and offers many advantages in terms of reaction efficiency Esters of N-tert-butoxycarbonyl (BOC) amino acids are widely used in peptide chemistry and in preparing several chiral auxiliaries such as β-amino alcohols, oxazolidinones, and α-amino aldehydes. N-Boc amino esters can be prepared either from amino esters by reacting with di-tert-butyl dicarbonate (diBoc), or from N-Boc amino acids by esterification. Both methods are unsatisfactory. In the first method, the reaction with diBoc requires alkaline conditions in which the ester group is not stable, although in some cases weaker bases can be used these require longer reaction times, and the yields are moderate. In the second method, commonly used esterification protocols involving reaction with an alcohol in the presence of acid catalysts such as HCl, H2SO4, thionyl chloride, PTSA, etc. cannot be used since the Boc group is unstable in acidic conditions.

Pesticide Biochemistry: Camptothecin, a quinolone alkaloid extracted from Camptotheca acuminata Decne, exhibits potential insecticidal activities against various insect species. The extensive applications of CPT on controlling pests have been prevented by its two major drawbacks. First, CPT has poor solubility in water and weak cuticular penetration. Second, the lactone ring of CPT is unstable which makes it easy transform to inactive carboxylate compound. introduction of t-Boc amino acids to 20-position on CPT improves contact assay and cytotoxicity of most derivatives toward Spodoptera exigua but reduces the inhibitory effect on relaxation activity of Spodoptera exigua topoisomerase I.

boc-amino-acids

References

  1. CHANKESHWARA S, CHAKRABORTI A. Catalyst-free chemoselective N-tert-butyloxycarbonylation of amines in water[J]. Organic Letters, 2006, 8(15): 3259–62.
  2. PRASHAD M, HAR D, HU B, etc. Process Development of a Large-Scale Synthesis of TKA731:? A Tachykinin Receptor Antagonist[J]. Organic Process Research & Development, 2004, 8(3): 330–340.
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