Izvorni znanstveni članak

https://doi.org/10.5562/cca2591

Synthesis of Orthogonally Protected Muramic Acid Building Blocks for Solid Phase Peptide Synthesis

Kristina Vlahoviček-Kahlina ; Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička c. 54, 10000 Zagreb, Croatia
Andreja Jakas ; Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička c. 54, 10000 Zagreb, Croatia

Sažetak

Muramic acid is found in many peptide natural products containing oligo(poly)saccharide moieties. Taking into consideration that the Fmoc methodology is routinely used for solid-phase peptide synthesis, preparation of orthogonally protected muramic acid building blocks for total solid-phase synthesis of these natural products is of particular practical importance. Herein a simple and efficient synthesis of benzyl 2-amino-4,6-O-benzylidene-3-O-[(R)-1-carboxyethyl]-2-deoxy-N-9-fluorenylmethyloxycarbonyl-α-D-glucopyranoside (6) from N-acetylglucosamine (1) is described. Important improvements over previous synthetic approaches to glucopyranosides 2 (benzyl 2-acetamido-2-deoxy-α-D-glucopyranoside) and 3 (benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-α-D-glucopyranoside), key building blocks in preparation of 6, include synthesis simplification and efficient isolation and purification. Optically pure (S)-2-chloropropionic acid 7 was prepared and introduced to the positon 3-O of sugar moiety to give compound 4 (benzyl 2-acetamido-4,6-O-benzylidene-3-O-[(R)-1-carboxyethyl]-2-deoxy-α-D-glucopyranoside) with the (R)-configuration of the lactyl side-chain in excellent overall yield and optical purity. Deacetylation of amino group gave compound 5 (benzyl 2-amino-4,6-O-benzylidene-3-O-[(R)-1-carboxyethyl]-2-deoxy-α-D-glucopyranoside) suitable for incorporation of the Fmoc protecting group to give protected muramic acid derivative 6, a useful building block in peptide synthesis.

Ključne riječi

dipeptide isostere; muramic acid; solid phase peptide synthesis (SPPS); sugar amino acid (SAA)

Hrčak ID:

141987

URI

https://hrcak.srce.hr/141987

Datum izdavanja:

20.7.2015.

Posjeta: 2.604 *