Synthesis of New Hexosaminyl D‐ and L‐chiro‐Inositols Related to Putative Insulin Mediators

Abstract

We have developed an efficient synthetic strategy to HexNH2‐α(1⇄3)‐L‐chiro‐inositol (XII−XIII) and HexNH2‐α(1⇄2)‐D‐chiro‐inositol (XIV−XV) based on the regio and stereoselective glycosylation of tetrabenzoyl‐L‐chiro‐inositol 2 and tetrabenzyl‐D‐chiro‐inositol 14. Compounds XII−XV may constitute the central structural motifs of inositolphosphoglycans, which have been proposed as putative insulin mediators, and their syntheses have been designed on the basis of biosynthetic considerations. The syntheses of XII−XIII and XIV−XV involve the selective monoglycosylation of an L‐chiro inositol diequatorial diol system (2) and a D‐chiro inositol axial/equatorial diol system (14), respectively. To establish the experimental conditions to achieve the best reactivity−selectivity balance, the glycosylation reactions were studied using D‐gluco‐ and D‐galacto‐configured 2‐azido‐2‐deoxytrichloacetimidate glycosyl donors with different reactivities. The results obtained provide a practical synthetic route and new reactivity−selectivity data. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Simultaneous Regio‐ and Enantiodifferentiation in Carbohydrate Coupling

“…The clear influence of the absolute configuration of the acceptor could not be observed when a similar study was carried out with the tetrabenzylated glycosyl acceptors 24 D and 24 L which were prepared from 1 D 10c and 1 L ,16 respectively, as indicated in Scheme for the D enantiomer. These syntheses required long protecting group manipulations due to the difficulties found when direct benzylation of the silylated tetraol D ‐ chiro ‐inositol derivative was tried instead of the benzoylation that affords 1 D and 1 L 10c,16. The results of the glycosylation reactions with acceptors 24 D and 24 L are presented in Table 2 and Figure 4.…”

“…That could be the case of the higher ratio of glycosylation of hydroxy groups at C3‐positions, even being the most hindered one, compared to OH‐2 in α‐altrose diol acceptor derivatives described by Fraser‐Reid and collaborators 8b. This fact could also explain the low glycolysation tendency of the axial hydroxy group at C1 vs. C2 in D ‐ chiro ‐inositol 1,2‐ syn diol acceptors 10c…”

“…We have previously shown that the coupling of L ‐ chiro ‐inositol terabenzoate 1 L with trichloroacetimidate 2 gave a 6.4:1 mixture of the α(1→3) ( 3 ) and the α(1→2) ( 4 ) pseudodisaccharides in 67 % combined yield (Scheme ). Similarly, the glycosylation of 1 L with 5 gave a 7:1 mixture of the α(1→3) ( 6 ) and the α(1→2) ( 7 ) compounds in 48 % overall yield 10c. The regioselectivity was poorer but followed the same trend in the glycosylation with the less reactive trichloroacetimidate 8 which afforded a 2:1 mixture of the α(1→3) ( 9 ) and the α(1→2) ( 10 ) pseudodisaccharides in 78 % overall yield.…”

Synthesis of galactosaminyl d-chiro-inositols

“…While several differentially protected 8 chiro-inositols have been synthesized, [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] we sought a general strategy for the syntheses of a complete set of penta-O-benzyl-D D-chiro-inositols, each with a different unprotected hydroxyl group for glycosylation. Since chiro-inositol has a C 2 axis of symmetry, the set consists of only three different penta-O-benzyl-chiro-inositols: 8, 9, and 10.…”

“…The a anomers of the unacetylated disaccharides have been previously prepared by other methods. 20,21,24 …”