Firstly, I recommend to look through the papers by Bara, Y. et al.
Chem. Ber. 1978, 111, 1029 & 1045 in which the synthesis of
cyclopenta-Gly is detailed (20% yield).
I also enclose few useful refs; [1-3] are reviews.
As for solid phase approach, you should keep in mind that gel-type
supports do not provide effective isolation of polymer-bound reactive
groups. Next, it is well documented that cyclization in solution is
seriously complicated with oligomerization when performed at peptide
concentrations higher than 0.1-1 mM. Exceptions (due to the favorable
precursor conformation) from this general trend are rare.
To keep the same high dilution conditions during SP cyclization,
peptide loading should be 0.1-1 uM/per 1 ml of swollen peptide-resin
(PR) which has specific bed volume in the range 5-7 lm/per 1 g of dry
PR. Therefore optimal initial resin loading should be reduced to few
micro(!)moles/dry g.
So, don't be over-enthusiastic about SPPS in this particular case.
DPPA (diphenylphosphorylazide) is still one of the best cyclization
agents. You can safely apply it directly to N,C-free linear precursor.
Note, that popular HBTU/HATU will produce a lot of
N-tetrametylguanidinium by-product under these conditions.
I wish you success in the ongoing cyclization experiments.
Sincerely yours
Igor
1. Ovchinnikov Yu.A. and Ivanov V.T. The cyclic peptides: structure,
conformation, and function..- In: The Proteins. /Neurath, H. and Hill,
R.L., Eds., Vol.5, Academic Press: New York, London , 1982, v.,
pp.307-642 .
2. Beck-Sickinger, A.G. Synthesis of conformationally restricted
peptides.- Methods Mol Biol, 1997, v.73, pp.61-73.
3. Blackburn, C. and Kates, S.A. Solid-phase synthesis of cyclic
homodetic peptides.- Methods Enzymol, 1997, v.289, pp.175-98.
4. Ji, A.X. and Bodanszky, M. Cyclization studies with a model
pentapeptide.- Int J Pept Protein Res, 1983, v.22(5), pp.590-6.
5. Schmidt, U. and Langner, J. Cyclotetrapeptides and
cyclopentapeptides: occurrence and synthesis.- J Pept Res, 1997,
v.49(1), pp.67-73.
6. Sowemimo, V., Scanlon, D., Jones, P. and Craik, D.J. Synthesis of
cyclic penta- and hexapeptides: a general synthetic strategy on DAS
resin.- J Protein Chem, 1994, v.13(3), pp.339-46.
7. Kates,S.A., Sole,N.A., Johnson,C.R., Hudson,D., Barany,G. and
Albericio,F. A novel, convenient, three-dimensional orthogonal strategy
for solid-phase synthesis of cyclic peptides..- Tetrahedron Lett., 1993,
v.34(10), pp.1549-1552.
------------------------------------------------
Igor L. Rodionov
Laboratory of Peptide Chemistry
Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry
Science Avenue 6
Pushchino, Moscow Region
142292, Russian Federation
E-mail: <rodionov@fibkh.serpukhov.su> or <Igor_Rodionov@iname.com>
Fax: (0967)-79-05-27
Phones: (0967) 73 54 42; private: (0967) 73 58 26
http://www.fibkh.serpukhov.su/