Furanosides, stereoselective synthesis

By using either one of these photosystems, one-electron (3-activation of a,(3-unsaturated carbonyl compounds produced carbon-centered radical precursors which cyclize efficiently and stereoselectively to tethered activated olefins or carbonyl groups. The 1,2-anti-stereochemistry observed contrasts with the general trend of syn-stereochemistry expected in 5-hexenyl radical cyclizations. Application of this methodology was successfully demonstrated by the stereoselective synthesis of optically pure C-furanoside, starting from L-tartaric acid (Scheme 38) [57,58]. 

Pandey, G., Hajra, S., Ghorai, M.K., and Kumar, K.R. (1997) Visible light initiated photosensitized electron transfer cyclizations of aldehydes and ketones to tethered a,p-unsaturated esters stereoselective synthesis of optically pure C-furanosides. Journal of Organic Chemistry, 62, 5966-5973. 

Hou D, Lowary TL. Stereoselective synthesis of 2-deoxy-furanosides from 2,3-anhydro-furanosyl thioglycosides. Org. Lett. 2007 9 4487 90. 

Another stereochemically interesting feature was observed in the synthesis of the gilvocarcins [17]. The al preference is not obvious for the furanoside-series, and indeed the outcome depends heavily on the metal center of the Lewis acid—a-selec-tivity is obtained with Hf, /3-selectivity with Sn (Eq. 7). Although the difference might reflect the behavior of the eoordinated species, many factors inhibit understanding of the true origin of the stereoselectivity. 

The effect of a free OH group is usually much more pronounced than that of the protected one. For example, oxiranes 58 and 59 were obtained with high stereoselectivity (directed by the free OH), although both oxy-substituents act in the opposite directions [ 1,44] (O Fig. 12). When the epoxidation is performed not on allylic alcohols but allylic esters the selectivity of this process is low both possible oxiranes are obtained in comparable amounts. The stereoselective formation of the 2-3-epoxides can be achieved also by the Sn2 process. Recently, Lowary proposed an efficient synthesis of 2,3-epoxy-arafci o-furanoside 61 from the parent glycoside 60 in a sequence of reactions presented in Scheme 20 [45]. Such anhydrosugars are convenient precursors for further functionalization at either the C-2 or C-3 position. 

Subsequently, 22a was converted into the per-benzylated glycosyl donor 22b by sequential deacetylation and benzylation under standard conditions in 87 % yield. Glycosylation of acceptor 23 with 22b was performed in the presence of TMSOTf yielding the disaccharide 24 in 80 % yield with complete 1,2-cis stereoselectivity. Ferrieres and Plusquellec described the synthesis of per-acetylated thiopyrimidinyl furanosides and their application to anomeric phosphorylation 32, 33). 

Recendy, we described a useful sequence where Michael-acceptor sulfoxides 30 were obtained in two steps from homopropargylic alcohols 29 by radical addition of thiophenol and oxidation with sodium periodate. The unsaturated sulfoxides were used in a highly stereoselective intramolecular oxa-Michael reaction. The sequence provided stereoselective functionalization of the sulfoxide moiety, and the products 31 proved to be useful in the synthesis of modified furanosides 32. This represents a good exanple where sugars are prepared from acyclic precursors. The Michael addition was followed by a hydrolytic Pummerer reaction, yielding protected a-hydroxy aldehydes tScheme 20.8) that upon acidic treatment afforded 3-substituted ribofuranoses. 

The furanoside-based dienophiles 3 and 4 undergo stereoselective Diels-Alder cycloaddition with cyclopentadiene and 1,3-cyclohexadiene to give exclusively the exo-adducts 5 and 6 respectively adduct 5 (n=l) has been converted to the complex cyclopentane 7 (Scheme 2).5 A lengthy synthesis of PGF2a from D-mannitol has been described with the carbohydrate unit contributing stereochemical centres in both the cyclopentane ring and the side chain. ... 

SCHEME 38.33. Proposed stereoselectivity model for 1,2-migration-glycosylation, and synthesis of 2-deoxy-(3-furanoside. 

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