Hantzsch-type three-component approach to a new family of carbon-linked glycosyl amino acids. synthesis of C-glycosylmethyl pyridylalanines

被引:26
作者
Dondoni, Alessandro
Massi, Alessandro
Aldhoun, Mohammad
机构
[1] Univ Ferrara, Chim Organ Lab, Dipartimento Chim, I-44100 Ferrara, Italy
[2] Univ Ferrara, Cent RMN, I-44100 Ferrara, Italy
关键词
D O I
10.1021/jo071221r
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
[GRAPHICS] C-Glycosylmethyl pyridylalanines reported in this paper constitute a novel family of glycosyl amino acids that contain a pyridine ring linking the carbohydrate and amino acid residues. These amino acids may serve to prepare nonnatural glycopeptides displaying firmly bound carbohydrate fragments through a rigid and highly stable tether. A viable route to these new hybrid molecules has been opened via thermally induced Hantzsch-type cyclocondensation using an aldehyde-ketoester-enamino ester system. To one of these reagents was attached a C-glycosyl residue, while to another was bound an amino acid fragment. In a one-pot optimized methodology, the dihydropyridine was not isolated while its purification was carried out by removal of unreacted material and side products using polymer-supported scavengers. Then the dihydropyridine (mixture of diastereoisomers) was oxidized by a polymer-bound oxidant to give the target pyridine bearing the two bioactive residues. In this way a range of eight compounds (58-68% yield) was prepared in which the elements of diversity were (i) the gluco and galacto configurations of the pyranose ring, (ii) the alpha- and beta-configurations at the anomeric center, and (iii) the positions of the carbohydrate and amino acid sectors in the pyridine ring. The orthogonal functional group protection in these amino acids allowed their easy incorporation into oligopeptides via sequential amino and carboxylic group coupling.
引用
收藏
页码:7677 / 7687
页数:11
相关论文
共 62 条
[1]   Unification of reaction metrics for green chemistry: Applications to reaction analysis [J].
Andraos, J .
ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2005, 9 (02) :149-163
[2]  
[Anonymous], [No title captured]
[3]   Stereoselective synthesis of NEO-C-glycopeptide building blocks: Towards a flexible and control-oriented design as probes for carbohydrate-protein interactions [J].
Arya, P ;
Dion, S ;
Shimizu, GKH .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1997, 7 (12) :1537-1542
[4]   USE OF L-ASPARTIC ACID BETA-SEMIALDEHYDE IN THE SYNTHESIS OF MORE COMPLEX NONPROTEIN AMINO-ACIDS [J].
BALDWIN, JE ;
FLINN, A .
TETRAHEDRON LETTERS, 1987, 28 (31) :3605-3608
[5]   A novel neoglycopeptide building block [J].
Bartolozzi, A ;
Li, BQ ;
Franck, RW .
BIOORGANIC & MEDICINAL CHEMISTRY, 2003, 11 (13) :3021-3027
[6]  
Beer T., 1995, BIOCHEMISTRY-US, V34, P11785
[7]  
Bezouska K., 2002, Rev. Mol. Biotechnol, V90, P269, DOI DOI 10.1016/S1389-0352(01)00064-2
[8]   Multiple component approaches to C-glycosyl β-amino acids by complementary one-pot mannich-type and reformatsky-type reactions [J].
Dondoni, A ;
Massi, A ;
Sabbatini, S .
CHEMISTRY-A EUROPEAN JOURNAL, 2005, 11 (23) :7110-7125
[9]   Cross-metathesis of C-allyl iminosugars with alkenyl oxazolidines as a key step in the synthesis of C-iminoglycosyl α-amino acids.: A route to iminosugar containing C-glycopeptides [J].
Dondoni, A ;
Giovannini, PP ;
Perrone, D .
JOURNAL OF ORGANIC CHEMISTRY, 2005, 70 (14) :5508-5518
[10]   Assembling heterocycle-tethered C-glycosyl and α-amino acid residues via 1,3-dipolar cycloaddition reactions [J].
Dondoni, A ;
Giovannini, PP ;
Massi, A .
ORGANIC LETTERS, 2004, 6 (17) :2929-2932