Methods of Non-a-Amino Acid Synthesis, 2nd Edition

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6

Biologically Important

Amino Acids

Non-α-amino acids are known to play a prominent role in nature and in important

biological compounds. Indeed, there are many examples of non-α-amino acids that

possess important biological properties. This chapter discusses several types of these

amino acids in order to illustrate both the impetus for synthesizing amino acids and

the various structural types that are found. Those synthetic approaches presented

in this chapter span the range of methods presented in the rst ve chapters, and

include some new strategies as well.

6.1 PEPTIDES AND PROTEINS

6.1.1 as Residues in PePtides and PRoteins

Natural peptides are obviously important biomolecules, and the structure is usually

a poly(α-amino acid) structure such as 1. Non-α-amino acids are found in many

proteins, or they are the target of important enzymes. This section will describe

examples in which these amino acids are important components of peptides or pro-

teins. The examples are presented in a somewhat random order in one sense, but they

are presented in this manner to illustrate that incorporation of non-α-amino acids is

rather widespread.

There is considerable research on the preparation and study of peptides consist-

ing of homologated proteinogenic amino acids.

1

There are unnatural β-peptides

that contain β-amino acids (see 2 or 3). Conformational studies have been reported

for β-amino acids and the so-called β-peptides

2

generated from such amino acids.

3

Peptides such as 2 are known as β

3

-peptides,

4

and 3 are known as β

2

-peptides.

5

γ-Peptides such as 4 (γ 

4

-peptides) are known that contain γ-amino acids.

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As stated

by Voss and Ramos, “unlike natural α-peptide chains, which fold and unfold in a

1

Voss, G.; Ramos, G. Chemistry of Crop Protection: Progress and Prospects in Science and Regulation.

Wiley-VCH Verlag GmbH & Co. KgaA, Weinheim, FRG, 2004, pp. 17–29.

2

Cheng, R.P.; Gellman, S.H.; DeGrado, W.F. Chem. Rev. 2001, 101, 3219.

3

Beke, T.; Somlai, C.; Magyarfalvi, G.; Perczel, A.; Tarczay, G. J. Phys. Chem. B 2009, 113, 7918.

4

Matthews, J.L.; Braun, C.; Guibourdenche, C.; Overhand, M.; Seebach, D., in Enantioselective

Synthesis of b-Amino Acids, Juaristi, E., ed. Wiley-VCH, New York, 1997, pp. 105–126.

5

(a) Seebach, D.; Sifferlen, T.; Mathieu, P.A.; Häne, A.M.; Krell, C.M.; Bierbaum, D.J.; Abele, S. Helv.

Chim. Acta 2000, 83, 2849; (b) Micuch, P.; Seebach, D. Helv. Chim. Acta 2002, 85, 1567; (c) Seebach,

D.; Abele, S.; Gademann, K.; Guichard, G.; Hintermann, T.; Jaun, B.; Matthews, J.L.; Schreiber, J.V.;

Oberer, L.; Hommel, U.; Widmer, H. Helv. Chim. Acta 1998, 81, 932.

6

Hintermann, T.; Gademann, K.; Jaun, B.; Seebach, D. Helv. Chim. Acta 1998, 81, 983.