Dipeptide diastereomers
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 5, May, 2006
927
nine (∆AB). The ratio ∆RS >> ∆SS is observed for all
precipitate was filtered off, and THF was removed in vacuo. The
residue was dissolved in chloroform, and the solution was washed
with a 5% solution of NaHCO3, water, 5% HCl, with water
again (to pH ~7), and dried with Na2SO4. The chloroformic
solution was concentrated in vacuo to dryness. The residue was
analyzed by 1H NMR spectroscopy and HPLC.
AB
AB
dipeptides of Nꢀacetylphenylalanine. It should be noted
that in the (R,S)ꢀdipeptides the ∆RS
value increases
AB
with an increase in the size of the R substituent in the
COOR group of the valine fragment, whereas in the
(S,S)ꢀisomers the ∆SS value is almost zero (Table 3),
AB
i.e., the βꢀCH2 protons are equivalent (except for the case
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 04ꢀ03ꢀ32334)
and the Council on Grants of the President of the
Russia Federation (Program of State Support for Leading
Scientific Schools of the Russian Federation, Grant
NSh 1766.2003.3).
of R = But).
Individual diastereoisomers 7´—10´ synthesized by the
method excluding racemization were used for assignment
of the signals.11
It follows from the data presented in Table 2 that all
mixtures obtained are enriched in (R,S)ꢀdiastereomers
7″—10″ (up to 69—78%) regardless of the structure of the
R substituent in the ester group of peptides 7—10. A tenꢀ
dency to some decrease in the diastereoselectivity with an
increase in the size of the R substituent should also be
mentioned. Thus, the structure of the ester group exerts a
weak effect on the diastereoselectivity of the reaction,
unlike, e.g., the structure of the side chain of amino
acids.12 It is most likely that stereodifferentiation is deterꢀ
mined by the interaction of the groups closest to the reacꢀ
tion centers.
References
1. R. S. Ward, Tetrahedron Asymmetry, 1995, 6, 1475.
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3. S. Caddick and K. Jenkins, Chem. Soc. Rev., 1996, 25, 447.
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Asymmetry, 2000, 11, 1687.
7. N. L. Benoiton, K. Kuroda, and F. M. F. Chen, Tetrahedron
Lett., 1981, 22, 3361.
Experimental
8. H. S. Bevinakatti, R. V. Newadkar, and A. A. Banerji,
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9. J. Z. Crich, R. Brieva, P. Marquart, R.ꢀL. Gu, S. Flemming,
and C. J. Sih, J. Org. Chem., 1993, 58, 3253.
10. L. Xie, W. Hua, A. S. C. Chan, and Y.ꢀC. Leung, Tetraꢀ
hedron Asymmetry, 1999, 10, 4715.
11. The Peptides. Analysis, Synthesis, Biology. V. 1. Major
Methods of Peptide Bond Formation, Eds E. Gross and
J. Meienhofer, Academic Press, New York—San Francisco—
London, 1979.
12. V. P. Krasnov, E. A. Zhdanova, N. Z. Solieva, L. Sh.
Sadretdinova, I. M. Bukrina, A. M. Demin, G. L. Levit,
M. A. Ezhikova, and M. I. Kodess, Izv. Akad. Nauk, Ser.
Khim., 2004, 1278 [Russ. Chem. Bull., Int. Ed., 2004,
53, 1331].
13. A. A. Gershkovich and V. K. Kibirev, Khimicheskii sintez
peptidov [Chemical Synthesis of Peptides], Naukova Dumka,
Kiev, 1992, 360 pp. (in Russian).
1
H NMR spectra were recorded on a Bruker DRX 400 specꢀ
trometer (400.13 MHz) using Me4Si as internal standard. The
synthesized compounds were analyzed by HPLC on a Milikhrom
4ꢀUF chromatograph (Silasorbꢀ60 as sorbent, column 64×2 mm,
detection at 230 nm, elution rate 200 µL min–1). Melting points
were determined on a Boetius heating stage and used without
correction.
Methyl and ethyl (S)ꢀvalinate hydrochlorides and benzyl
(S)ꢀvalinate pꢀtoluenesulfonate were synthesized as described
previously.13 tertꢀButyl (S)ꢀvalinate acetate was synthesized acꢀ
cording to a known procedure.14
Synthesis of alkyl Nꢀacetylꢀ(S)ꢀphenylalanyl and Nꢀacetylꢀ
(R)ꢀphenylalanyl (S)ꢀvalinates 7´—10´ and 7″—10″ (general proꢀ
cedure). Triethylamine (0.61 mL, 4.34 mmol) and isobutyl
chloroformate (0.48 mL, 3.62 mmol) were added dropwise with
stirring to a solution of Nꢀacetylꢀ(S)ꢀphenylalanine (0.75 g,
3.62 mmol) in THF (17 mL) at –10—–15 °C. The reaction
mixture was stirred for 30 min at –13 °С, and then a mixture
obtained by stirring of the corresponding salt of (S)ꢀvaline ester
(3.62 mmol) with Et3N (0.51 mL, 3.62 mmol) in THF (9 mL)
and cooled to –10 °C was added. The reaction mixture was
stirred for 1 h at –10—–15 °C, for 1 h at 0 °C, and for 3 h at
~20 °C and then kept without stirring for ~16 h at ~20 °C. The
14. V. P. Krasnov, G. L. Levit, I. M. Bukrina, A. M. Demin,
O. N. Chupakhin, and Ii Uk Yoo, Tetrahedron Asymmetry,
2002, 13, 1911.
Received January 25, 2006;
in revised form April 13, 2006
Zhdanova
