Abstract:
:alpha,alpha-Disubstituted amino acids are alpha-amino acids in which the hydrogen atom at the alpha-position of the L-alpha-amino acid is replaced with an alkyl substituent. The introduction of an alpha-alkyl substituent changes the properties of amino acids, with the conformational freedom of the side chain in the amino acids and the secondary structure of their peptides being especially restricted. The author developed a synthetic route of optically active alpha-ethylated alpha,alpha-disubstituted amino acids using chiral cyclic 1,2-diol as a chiral auxiliary. It was found that the preferred secondary structure of peptides composed of chiral alpha-ethylated alpha,alpha-disubstituted amino acids is a fully extended C5-conformation, whereas that of peptides composed of chiral alpha-methylated alpha,alpha-disubstituted amino acids is a 3(10)-helical structure. Also, a new chiral cyclic amino acid; (3S,4S)-1-amino-3,4-di(methoxy)cyclopentanecarboxylic acid {(S,S)-Ac5c(dOM)}, and a bicyclic amino acid; (1R,6R)-8-aminobicyclo[4.3.0]non-3-ene-8-carboxylic acid {(R,R)-Ab5,6= c}, in which the alpha-carbon atom is not the chiral center but chiral centers exist at the side-chain cycloalkane skeleton, were designed and synthesized. The (S,S)-Ac5c(dOM) hexa- and octapeptides preferentially formed left-handed (M) helices, in which the helical-screw direction is exclusively controlled by the side-chain chiral centers. Contrary to the left-handed helices of (S,S)-Ac(5)c(dOM) peptides, the (R,R)-Ab5,6= c hexapeptide formed both diastereomeric right-handed (P) and left-handed (M) helices, and the twelve chiral centers at the side chain showed no preference for helical-screw direction. Thus, the chiral environment at the side chain is important for the control of helical-screw direction. Furthermore, the author designed a new class of chiral cyclic alpha,alpha-disubstituted amino acids that have pendant chiral centers at the substituent of the delta-nitrogen atom. The synthetic route would provide various optically-active cyclic alpha,alpha-disubstituted amino acids bearing a pendant chiral moiety.
journal_name
Chem Pharm Bull (Tokyo)journal_title
Chemical & pharmaceutical bulletinauthors
Tanaka Mdoi
10.1248/cpb.55.349subject
Has Abstractpub_date
2007-03-01 00:00:00pages
349-58issue
3eissn
0009-2363issn
1347-5223pii
JST.JSTAGE/cpb/55.349journal_volume
55pub_type
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