Levoglucosenone synthesis

R. Blattner and D. M. Page, Radical addition to levoglucosenone, synthesis of anhydrosugar herbicide analogues, J. Carbohydr. Chem. 132 21 (1994). 

Scheme 2.6)—relatively large amounts can be amassed quickly levoglucosenone has been used for the synthesis of a diverse variety of natural products in enantio-pure form." ... 

Witczak, Z. J. Chhabra, R. Chen, H. Xie, X. Q., Thiosugars.2. A novel approach to thiodisaccharides - The synthesis of 3-deoxy-4-thiocellobiose from levoglucosenone. 

The synthesis started with levoglucosenone 4, available by the pyrolysis of cellulose, e.g. old newspapers. Bromination-dehydrobromination gave the enantiomerically-pure Diels-Alder dienophile 5, which was combined with isoprene to give predominantly the crystalline adduct 1. Hydrolysis and acetylation led to 6, which was carried on to the geometrically-defined allylic alcohol 7 via reduction with Zn-Cu couple. Overman rearrangement of 7 proceeded with high facial control, to give 8. 

K. Matsumoto, T. Ebata, K. Koseki, H. Kawakami, and H. Matsushita, Synthesis of D-allosan from levoglucosenone, Heterocycles, 32 (1991) 2225-2240. 

The chiral bicyclic enones, levoglucosenone, isolevoglucosenone, and new functionalized L-arabinose enone possess excellent reactivity and functionality. Their properties mid application as convenient precursors in the synthesis of many attractive templates or intermediates of complex natural products are reviewed. These compounds are attracting increasing interest due to their structural rigidity and ability for stereoselective functionalization without protection, deprotection sequences necessary in many synthetic organic methodologies. 

All the research to date supports the preferential formation of levoglucosenone despite the possibility of double dehydration with alternative formation of isolevoglucosenone. This formation has never been detected in the pyrolysate and is only available through a total synthesis. 

Many other laboratories (2-11,33-45) have made significant contributions to the chemistry of iso- and levoglucosenone. Further, interdisciplinary attempts to utilize the potential of both enones and their functionalized analogs in organic synthesis will be forthcoming. 

Levoglucosenone and its functionalized analogue have been synthesized from furan by employing either enzymatic resolution or asymmetric synthesis. The potential of the latter as a chiral building block has been demonstrated by synthesis of all eight hexose diastereomers and some other natural products. 

Besides the cellulose pyrolysis producing levoglucosenone (-)-l, syntheses of both enantiomers of 1 have been reported.1,3 However, these methods use natural carbohydrate precursors and the results are practically less than satisfactory. We, therefore, explored first the synthesis of levoglucosenone 1 without using a naturally occurring starting material. 

Synthesis of a Levoglucosenone-Type Chiral Building Block... 

Having established the chiral synthesis of levoglucosenone 1 and its functionalized analogues in both enantiomeric forms, we next investigated the exploitation of 26, the functionalized isolevoglucosenone, for the enantiocontrolled construction of natural products on the basis of its inherent convex-face selectivity and functionality, in particular, the alkoxymethyl handle for the acetal cleavage. 

Easily prepared from glycols, enones have been investigated as dienophiles. They react with butadiene under Lewis acid catalysis to form chiral cyclohexenes used in the synthesis of compactin analogs [353]. Levoglucosenone has been used in a Diels-Alder reaction with acetoxy-butadiene to construct a part of the indole alkaloid reserpine [354], and in synthetic studies toward tetrodotoxin [355]. Analogs of the anthracycline rhodomycinone have been similarly prepared [356]. [4 + 2]-Cycloaddition of the same enone with silyloxydiene allowed the creation of the fused ring system present in actinobolin [357]. 

Mori, M, Chuman, T, Kato, K, Mori, K, A stereoselective synthesis of natural (45,65,75)-serricomin, the sex pheromone of cigaret beetle, from levoglucosenone, Tetrahedron Lett., 23, 4593-4596, 1982. 

Witczak, Z J, Synthesis of C-glycosyl compounds and other natural-products from levoglucosenone. Pure Appl. Chem., 66, 2189-2192, 1994. 

Isobe, M, Fukami, N, Nishikawa, T, Goto, T, Synthesis of chiral cyclohexanes from levoglucosenone and its application to an indole alkaloid reserpine, Heterocydes, 25, 521-532, 1987. 

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