Pyranosides, annulated

N. Naz, T. H. Al-Tel, Y. Al-Abed, and W. Voelter, Synthesis of polyfunctionalized bis-annulated pyranosides Useful intermediates for triquinane synthesis, Tetrahedron Lett. 35 8581 (1994). 

B. J. Fitzsimmons and B. Fraser-Reid, Annulated pyranosides as chiral synthons for carbo-cyclic systems. Enantiospecific routes to both (+) and (-) chrysanthemum carboxylic acids from a single progenitor, J. Am. Chem. Soc. 101 6123 (1979). 

J. L. Primeau, R. C. Anderson, and B. Fraser-Reid, Annulated pyranosides Some cyclohexano and cyclopentano-sugars, J. Chem. Soc. Chem. Commun. p. 6 (1980). 

R. Tsang and B. Fraser-Reid, Pyranose ct-enones provide ready access to functionalized trans-decalins via bis annulated pyranosides obtained by intramolecular Diels-Alder reactions a key intermediate for forskolin, J. Org. Chem. 57 1065 (1992). 

A. A. Ghini, C. Bumouf, J. C. Lopez, A. Olesker, and G. Lukacs, Intramolecular Diels-Alder reactions on pyranose trienes. Stereoselective access to bis-annulated pyranosides. Tetrahedron Lett. 37 2301 (1990). 

R. Tsang and B. Fraser-Reid, Serial radical cyclization via a vinyl group immobilized by a pyranoside. A route to bis-annulated pyranosides, J. Am Chem Soc. 108 2116 (1986). 

I. Marco-Contelles and J. Ruiz-Caro, Iridoids from carbohydrates via Pauson-Khand reaction synthesis of advanced highly oxygenated cyclopentane-annulated pyranosides from D-glucal derivatives,. /. Org. Chem., 64 (1999) 8302-8310. 

Cyclic, 6-membered carbohydrate a-enones have also been used as dienophiles for the preparation of annulated pyranosides. Lnone 11a produces a single adduct 12a in an aluminum chloride catalyzed addition to 1,3-butadiene (2a)13a. Enone 11b behaves similarly, when treated with 1,3-butadiene in the presence of a six-fold excess of aluminum chloride13b. 

The plan devised for actinobolin grew out of the observation that sugar-derived a-enones, such as FI, underwent Diels-Alder reactions from the P-face to give annulated pyranosides, such as FII, as the only products [64, 65]. In addition, preliminary experiments had shown that the reactions of these bicyclic molecules were dominated by the conformational preferences of the pyranosidic moiety, these results being in accordance with the predictions of the anomeric effect [66]. Transformations on the carbocyclic annulus could therefore be undertaken on the basis of this established conformational preference. 

Methyl 2,3,6-trideoxy-a-D-hex-2-enopyranosid-4-ulose, F2, was readily prepared from triacetyl glucal FI [67], as summarized in Scheme 20. Reaction of this material with Danishefsky s diene [68] gave the annulated pyranoside F3 in 93% yield as a single diastereomer, in keeping with precedents. 

By corollary, these data indicate that in spite of its heavy freight of axial substituents, the annulated pyranoside F12 resided in the conformation which... 

The synthesis and use of glycal derivatives in the preparation of staurosporine and en/-staurosporine is mentioned in Chapter 24 and an investigation into the isomerization of 2-oxo-pyranosides in pyridine affording a hydroxyenone product is covered in Chapter 15. The synthesis of a 1,2-unsaturated C-2 branched, 3,4-annulated sugar from a 2,3-unsaturated pyranose bearing a 4-0-allyl substituent is covered in Chapter 14. 

In the reaction of allylic ethers with aryl halides, elimination of /t-alkoxy group occurs in some cases. Intramolecular reaction of the glycal 127 afforded the cis-fused pyrano[2,3-c]pyran 129 via deoxypalladation as shown by 128 [74]. On the other hand, ring cleavage of 130 occurs by deoxypalladation to give 132 via 131 [75]. Furthermore, the fcjiy-annulated pyranoside 134 was obtained by domino HR without elimination of the allyl ether group in 133 [76]. 

Cycloadditions to these enones yield annulated pyranosides , a number of which have become available in recent years in the authors laboratory (23). These bicyclic molecules open avenues for transcription of stereochemical information from sugars to carbocyclic systems, generalized procedures for which are currently not available. 

The annulated pyranoside (166) therefore possesses implements for diverse chemical manipulations as well as for the assembly of a wealth of chiral information and once this has been achieved, the cycloalkyl portion may be excised from the carbohydrate template at sites y or z. These are locations for possible periodate cleavage which would have to be carried out on the acyclic form (167). However, an alternative procedure for cleaving the bicyclic from (166) (X=0) is described in Scheme 43. 

The nature of the functional groups at carbons-1 and -4 i.e. the a and a positions of the cycloalkyl moiety) makes these cycloalkyl pyranosides intriguing chiral synthons. Thus in the case where annulation gives only one diastereomer of (166), it is possible to conceive of one set of manipulations, whereby one enantiomer would be produced, and a different set leading to the other enantiomer (Scheme 39 equation i). 

Thus in either case, the annulated pyranoside has the capability for enantioselective transformation. 

Carbohydrate Dienophiles. The most popular carbohydrate dienophiles to date have been pyranoid enones. Examples of Diels-Alder reactions involving carbohydrate 2,3-enones, 3,4-enones, and enolone esters are described below. In landmark studies reported by Fraser-Reid and co-workers, carbohydrate-derived 2,3-enones were shown to react with dienes to give cyclohexopyranosides (7- 3), Derivatives of methyl and ethyl 2,3-dideoxy- a D-g/ycero-hex-2-enopyranosid-4-ulose 1 underwent cycloaddition with butadiene in the presence of aluminum chloride, and with oxygen -substituted dienes in the absence of any catalyst. Annulated pyranosides 2 and 3 were obtained... 

Results. Regioisomeric dienes 2 and 3 underwent smooth cycloaddition reactions with sp2 and sp type dienophiles to give annulated pyranosides under thermal conditions in refluxing toluene. Under similar conditions the dieno-furano and -pyranosides reported by Fraser-Reid s and Giuliano s groups (38 and 39) failed to react with sp dienophiles although they are in principle more reactive 1-alkoxy-1,3-diene systems (33),... 

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