1.6- Anhydro bridge

A number of studies have now been made, notably by Buchanan and coworkers, with the object of determining the position of the equilibrium between the various pairs of interconvertible epoxides the findings are summarized in Chart I. For the dianhydro compounds, the epoxides that contain the free hydroxyl group quasi-axial, and that also have the possibility of a polar interaction between the epoxide ring and the 1,6-anhydro bridge, are clearly less stable than those in which it is quasi-equatorial, although the relative importance of these two factors is uncertain. The situation is less clear for the monocyclic epoxides. The half-chair conformations indicated are considered to be favored on the basis that the alkyl... 

Osmium tetraoxide-promoted reactions are stevically controlled that is, in all instances, the predominant formation of products having tram-oriented substituents at C-2 and C-3, and C-2 and CA, is ob-served, and, consequently, 277 and 279 preponderate over 278 and 280. However, for 2-0-acetyl-l,6-anhydro-3,4-dideoxy-/3-DL- n/t/iro-hex-3-enopyranose (281), reaction with osmium tetraoxide leads175 to 2-0-acetyl-l,6-anhydro-/3-DL-alloside (282 88%) and -galactoside (283 8%). Obviously, the 1,6-anhydro bridge creates greater steric... 

S. Ogawa and D. Aso, Chemical modification of the sugar moiety of methyl acarviosin synthesis and inhibitory activity of eight analogues containing a 1,6-anhydro bridge,... 

The reactivity of the nitroalkenes has been tested in the reaction with 1-thiosugars via conventional Michael reactions catalyzed by triethylamine. In both cases the stereoselective 1,2 addition proceeds by exclusive formation of an exo-adduct via formation of an S-linkage from the less hindered face of the molecule. As expected, the shielding effect of the 1,6-anhydro bridge effectively prevents the formation of the 2-equatorial product, yielding only the 2-axial products with a new quaternary center at C-2. This provides a stable molecule, as no epimerization or p-elimination is observed during the reduction of the nitro group. 

The thermal reaction produced 5 and 6 in a 3 2 ratio but the Lewis acid-catalyzed reaction gave a 1 1 ratio. We could not separate the two cycloadducts, but based the indicated constitution on analysis of the mass spectrum and lH NMR spectrum of the mixture of the two compounds. The stereochemistry was assigned on the basis that the Diels-Alder reaction is normally suprafacial-suprafacial18 and that for other cycloaddition reactions of levoglucosenone (2) the addition anti to the 1,6-anhydro bridge is favored.13 15... 

Michael additions19 to levoglucosenone (2) have been reported to go with high stereoselectivity. Only products derived by addition anti to the 1,6-anhydro bridge, exo products, have been reported for the Michael addition of methyl and w-pentyl cuprates20 and other Michael donors21 to levoglucosenone (2). 

Alcohols resulting from a first epoxide opening can indeed be submitted to a second sequence, as shown in Procter s approach to the macrolide antibiotic rosaramycin [36]. Here again the 1,6-anhydro bridge was chosen to lock the epoxides in the proper conformation to ensure completely regioselective introduction of an allyl chain at C2 in 28 (Scheme 11.9). Going back to the usual... 

This stereoselectivity as observed previously in levoglucosenone conjugate addition proceeds by the attack of an incoming nucleophile (thiol) at the alkene face opposite the 1,6-anhydro ring. The sterically hindered 1,6-anhydro bridge in isolevoglucosenone is, therefore assumed to effectively prevent formation of the opposite stereoisomer. 

Indeed, it was the use of partial esterification that enabled the great synthetic exploitation of levoglucosan (6), the most readily accessible 1,6-anhydrohexopyranose. The steric interaction of the axial 3-hy-droxyl group with the 1,6-anhydro bridge is accentuated on reaction with the bulkier acid chlorides or anhydrides in pyridine in such a way that this hydroxyl group is esterified substantially more slowly than the other axially oriented ones. Consequently, the dimolar esterification of 6 with p-toluenesulfonic anhydride,156 benzyloxycarbonyl chloride,520 p-toluenesulfonyl chloride,38 106,156 505 520 636 benzoyl chlo-... 

Another interesting dicnophile, l,6-anhydro-3,4-dideoxy-/ -D-g7)-rm>-hex-3-enopyranose-2-ulose (levoglucosenone, 9), is readily available by pyrolysis of waste papers. [4 + 2] Cycloaddition of cyclic28,29 and acyclic28,30 dienes to 9 proceeds with selective attack of the diene molecule to the face opposite the 1,6-anhydro bridge giving a mixture of endo- and exo-adducts. 

Horton and Bhata reported the synthesis of functionalized carbocycles by the Diels-Alder reactions of cyclopentadiene with levoglucosenone 14). The addition of cyclopentadiene occurred predominantly form the face of the enone opposite the 1,6-anhydro bridge, in the endo mode. 

In donor 29, the possible remote anchimeric assistance of the 6-O-acetyl group (vide infra) can also be of beneficial influence to the stereochemical outcome of the glycosylation at hand. To continue the synthesis of the guluronic add tetramer, the 1,6-anhydro-bridge in disaccharide 31 was opened, followed by selective anomeric... 

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