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Stereoselective synthesis of alpha- and beta-L-C-fucosyl aldehydes and their utility in the assembly of C-fucosides of biological relevance.
J Org Chem. 2004 Jul 23; 69(15):5023-36.JO

Abstract

An efficient synthesis of O-benzylated derivatives of the title sugar aldehydes via thiazole addition to tri-O-benzyl-l-fuconolactone followed by highly stereoselective deoxygenation of the resulting thiazolylketose and thiazole to formyl transformation is described. Wittig olefination of these aldehydes with galactopyranose and glucopyranose 6-phosphoranes and reduction of the resulting alkenes afforded alpha- and beta-linked (1-->6)-L-C-fucosyl disaccharides, namely, beta-L-C-Fuc-(1-->6)-alpha-D-Gal, alpha-L-C-Fuc-(1-->6)-alpha-D-Gal, and alpha-L-C-Fuc-(1-->6)-alpha-d-Glc. The alpha-anomer of the above C-fucosyl aldehydes was transformed into a C-fucosylmethyl triphenylphosphonium iodide from which the corresponding C-fucosylmethylene phosphorane was generated upon treatment with BuLi. This phosphorane reacted with the Garner aldehyde (N-Boc D-serinal acetonide) and its one-carbon higher homologue to give alkenes whose reduction and unveiling of the glycinyl group from the oxazolidine ring afforded C-fucosyl alpha-amino acids, namely alpha-L-linked C-fucosyl serines and C-fucosyl asparagines. As a final test of the synthetic utility of the title aldehydes, the beta-anomer was employed as starting material in the stereoselective synthesis of both R- and S-epimer L-C-fucosyl phenylhydroxy acetates. One epimer was obtained by reaction of the sugar aldehyde with phenylmagnesium bromide, oxidation of the resulting alcohol to ketone, addition of 2-lithiothiazole to the latter, and transformation of the thiazole ring into the carboxyl group through an aldehyde intermediate. The other epimer was obtained by the same procedure and inverting the timing of phenyl and thiazolyl group addition. In both routes, the key step establishing the configuration of the quaternary carbon atom of the aliphatic chain was the highly stereoselective addition of the organometal to the ketone intermediate.

Authors+Show Affiliations

Dondoni A
Dipartimento di Chimica, Laboratorio di Chimica Organica, Università di Ferrara, Via L. Borsari 46, 44100-Ferrara, Italy.
Catozzi N
No affiliation info available
Marra A
No affiliation info available

MeSH

AcetatesAldehydesAmino AcidsBiologyDisaccharidesGlycosidesMolecular StructureStereoisomerism

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15255731

Citation

Dondoni, Alessandro, et al. "Stereoselective Synthesis of Alpha- and beta-L-C-fucosyl Aldehydes and Their Utility in the Assembly of C-fucosides of Biological Relevance." The Journal of Organic Chemistry, vol. 69, no. 15, 2004, pp. 5023-36.
Dondoni A, Catozzi N, Marra A. Stereoselective synthesis of alpha- and beta-L-C-fucosyl aldehydes and their utility in the assembly of C-fucosides of biological relevance. J Org Chem. 2004;69(15):5023-36.
Dondoni, A., Catozzi, N., & Marra, A. (2004). Stereoselective synthesis of alpha- and beta-L-C-fucosyl aldehydes and their utility in the assembly of C-fucosides of biological relevance. The Journal of Organic Chemistry, 69(15), 5023-36.
Dondoni A, Catozzi N, Marra A. Stereoselective Synthesis of Alpha- and beta-L-C-fucosyl Aldehydes and Their Utility in the Assembly of C-fucosides of Biological Relevance. J Org Chem. 2004 Jul 23;69(15):5023-36. PubMed PMID: 15255731.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stereoselective synthesis of alpha- and beta-L-C-fucosyl aldehydes and their utility in the assembly of C-fucosides of biological relevance. AU - Dondoni,Alessandro, AU - Catozzi,Nicola, AU - Marra,Alberto, PY - 2004/7/17/pubmed PY - 2004/9/21/medline PY - 2004/7/17/entrez SP - 5023 EP - 36 JF - The Journal of organic chemistry JO - J Org Chem VL - 69 IS - 15 N2 - An efficient synthesis of O-benzylated derivatives of the title sugar aldehydes via thiazole addition to tri-O-benzyl-l-fuconolactone followed by highly stereoselective deoxygenation of the resulting thiazolylketose and thiazole to formyl transformation is described. Wittig olefination of these aldehydes with galactopyranose and glucopyranose 6-phosphoranes and reduction of the resulting alkenes afforded alpha- and beta-linked (1-->6)-L-C-fucosyl disaccharides, namely, beta-L-C-Fuc-(1-->6)-alpha-D-Gal, alpha-L-C-Fuc-(1-->6)-alpha-D-Gal, and alpha-L-C-Fuc-(1-->6)-alpha-d-Glc. The alpha-anomer of the above C-fucosyl aldehydes was transformed into a C-fucosylmethyl triphenylphosphonium iodide from which the corresponding C-fucosylmethylene phosphorane was generated upon treatment with BuLi. This phosphorane reacted with the Garner aldehyde (N-Boc D-serinal acetonide) and its one-carbon higher homologue to give alkenes whose reduction and unveiling of the glycinyl group from the oxazolidine ring afforded C-fucosyl alpha-amino acids, namely alpha-L-linked C-fucosyl serines and C-fucosyl asparagines. As a final test of the synthetic utility of the title aldehydes, the beta-anomer was employed as starting material in the stereoselective synthesis of both R- and S-epimer L-C-fucosyl phenylhydroxy acetates. One epimer was obtained by reaction of the sugar aldehyde with phenylmagnesium bromide, oxidation of the resulting alcohol to ketone, addition of 2-lithiothiazole to the latter, and transformation of the thiazole ring into the carboxyl group through an aldehyde intermediate. The other epimer was obtained by the same procedure and inverting the timing of phenyl and thiazolyl group addition. In both routes, the key step establishing the configuration of the quaternary carbon atom of the aliphatic chain was the highly stereoselective addition of the organometal to the ketone intermediate. SN - 0022-3263 UR - https://www.unboundmedicine.com/medline/citation/15255731/Stereoselective_synthesis_of_alpha__and_beta_L_C_fucosyl_aldehydes_and_their_utility_in_the_assembly_of_C_fucosides_of_biological_relevance_ DB - PRIME DP - Unbound Medicine ER -