Analogues of cell surface-associated carbohydrates or inhibitors of carbohydrateprocessing enzymes are of great pharmaceutical interest. Therefore, many synthetic efforts have been devoted to mimetics of this class of molecules, such as C-glycosyl compounds, which mimic glycosides by replacement of their exocyclic acetalic oxygen with a methylene group. The C-C linkage provides hydrolytic stability without greatly affecting the carbohydrate structure. The C-glycosyl scaffolds should be suitably functionalized in order to mimic their natural counterpart. Toward this aim, regioselective deprotection can be useful for the introduction of the required functional groups. Here, we present an easy procedure for the regioselective deprotection of 3-C-(2, 3, 4, 6-tetra-O-benzyl-α-d-glucopyranosyl)prop-1-ene (1)1 at glycon position 2 and of 3-C-(1, 3, 4, 6-tetra-O-benzyl-α-d-fructofuranosyl)prop-1-ene (4)2 at glycon position 1, respectively. Reaction of the fully benzylated C-glycosylpropene with molecular iodine affords a cyclic iodoether (2 or 5), which upon reductive elimination restores the double bond and a free hydroxyl group. The overall process results in regioselective debenzylation, giving products 3 and 6, respectively. The iodocyclization reaction first involves formation of the iodonium ion, on which the oxygen of the neighboring benzyl ether can act as a nucleophile in a 5-exotype cyclization, with subsequent loss of the benzyl group as benzyl iodide, in an intramolecular process (Scheme 17.1). This regioselective deprotection has been successfully used for the synthesis of a variety of biologically relevant carbohydrate mimetics, such as C-glycosyl derivatives of glucosamine and mannosamine, 3 mimics of α-and β-N-acetyllactosamine, 4 N-acetylgalactosamine, 5 C-glycosyl nojirimycins, 6-8 sugar azido acids, 9 fructose-derived scaffolds, 10 and rigid benzodiazepine chimeric scaffolds.11.

Cipolla, L., la Ferla, B., Rauter, A., Nicotra, F. (2016). Regioselective Debenzylation of C-Glycosylpropene. In Pavol Kováč (a cura di), Carbohydrate Chemistry: Proven Synthetic Methods: Volume 1 (pp. 167-173). CRC Press [10.1201/b11261-23].

Regioselective Debenzylation of C-Glycosylpropene

Cipolla, L;la Ferla, B;
2016

Abstract

Analogues of cell surface-associated carbohydrates or inhibitors of carbohydrateprocessing enzymes are of great pharmaceutical interest. Therefore, many synthetic efforts have been devoted to mimetics of this class of molecules, such as C-glycosyl compounds, which mimic glycosides by replacement of their exocyclic acetalic oxygen with a methylene group. The C-C linkage provides hydrolytic stability without greatly affecting the carbohydrate structure. The C-glycosyl scaffolds should be suitably functionalized in order to mimic their natural counterpart. Toward this aim, regioselective deprotection can be useful for the introduction of the required functional groups. Here, we present an easy procedure for the regioselective deprotection of 3-C-(2, 3, 4, 6-tetra-O-benzyl-α-d-glucopyranosyl)prop-1-ene (1)1 at glycon position 2 and of 3-C-(1, 3, 4, 6-tetra-O-benzyl-α-d-fructofuranosyl)prop-1-ene (4)2 at glycon position 1, respectively. Reaction of the fully benzylated C-glycosylpropene with molecular iodine affords a cyclic iodoether (2 or 5), which upon reductive elimination restores the double bond and a free hydroxyl group. The overall process results in regioselective debenzylation, giving products 3 and 6, respectively. The iodocyclization reaction first involves formation of the iodonium ion, on which the oxygen of the neighboring benzyl ether can act as a nucleophile in a 5-exotype cyclization, with subsequent loss of the benzyl group as benzyl iodide, in an intramolecular process (Scheme 17.1). This regioselective deprotection has been successfully used for the synthesis of a variety of biologically relevant carbohydrate mimetics, such as C-glycosyl derivatives of glucosamine and mannosamine, 3 mimics of α-and β-N-acetyllactosamine, 4 N-acetylgalactosamine, 5 C-glycosyl nojirimycins, 6-8 sugar azido acids, 9 fructose-derived scaffolds, 10 and rigid benzodiazepine chimeric scaffolds.11.
Si
Scientifica
Capitolo o saggio
C-glycosides, regioselective debenzylation, deprotection
English
Carbohydrate Chemistry: Proven Synthetic Methods: Volume 1
9781439866894
eBook ISBN 9781439866931
Cipolla, L., la Ferla, B., Rauter, A., Nicotra, F. (2016). Regioselective Debenzylation of C-Glycosylpropene. In Pavol Kováč (a cura di), Carbohydrate Chemistry: Proven Synthetic Methods: Volume 1 (pp. 167-173). CRC Press [10.1201/b11261-23].
Cipolla, L; la Ferla, B; Rauter, A; Nicotra, F
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/392270
Citazioni
  • Scopus 1
  • ???jsp.display-item.citation.isi??? ND
Social impact