Synthesis of libraries of thiazole, oxazole and imidazole-based cyclic peptides from azole-based amino acids. A new synthetic approach to bistratamides and didmolamides.
Treatment of a 1 : 1 mixture of the thiazole-based amino acids 8a and 8b with FDPP-i-Pr(2)NEt in CH(3)CN gave a mixture of the cyclic trimers 14, 15, 16 and 17 and the cyclic tetramers 19 and 23 in the ratio 2 : 7 : 5 : 8 : 1 : 1 and in a combined yield of 70%. Separate coupling reactions between the bisimidazole amino acid 45 and the thiazole/oxazole amino acids 43a and 42a in the presence of FDPP-i-Pr(2)NEt led to the bisimidazole based cyclic trimers 55 and 57 respectively (54-57%) and to the cyclic tetramer 56 (8-11%). Similar coupling reactions involving the bisthiazole and bisoxazole amino acids 49 and 47 with the imidazole/oxazole/thiazole amino acids 41a, 42a and 43a gave rise to the library of oxazole, thiazole and imidazole-based cyclic peptides 58, 59, 60, 61, 62, 63, 64 and 65. A coupling reaction between the bisthiazole amino acid 49 and the oxazole amino acid 73 led to an efficient (36% overall) synthesis of bistratamide H (67) found in the ascidian Lissoclinum bistratum. Coupling reactions involving oxazolines with thiazole amino acids were less successful. Thus, a coupling reaction between the phenylalanine-based oxazoline amino acid 71a and either the thiazole amino acid 8a or the bisthiazole amino acid 74 gave only a 2% yield of the cyclic hexapeptide didmolamide A (4) found in the ascidian Didemnum molle. Didmolamide B (68) was obtained in 9% yield from a coupling reaction between 74 and the phenylalanine threonine amino acid 72, using either FDPP or DPPA.
Bertram
Anna
A
School of Chemistry, University of Nottingham, Nottingham, UKNG7 2RD.
Maulucci
Nakia
N
New
Olivia M
OM
Mohd Nor
Siti Mariam
SM
Pattenden
Gerald
G
D000409:Alanine / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D002625:Chemistry, Organic / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D007093:Imidazoles / Q000737:chemistry*; D008956:Models, Chemical; D010080:Oxazoles / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry; D013844:Thiazoles / Q000737:chemistry*; D014561:Urochordata / Q000378:metabolism; D014633:Valine / Q000737:chemistry
D000596:Amino Acids; D007093:Imidazoles; D010080:Oxazoles; D010456:Peptides, Cyclic; D013844:Thiazoles; C521749:bistratamide H; C477590:didmolamide A; C477591:didmolamide B; D014633:Valine; D000409:Alanine