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The use of ring cleavage products of glycal derivatives in natural product synthesis

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Description: The synthesis of 3,4-di-O-acetyl-6-O-p-toluenesulfonyl-D-glucal from either 3,4,6-tri-O-acetyl-D-glucal or D-glucose was achieved. Starting with D-glucose gave a better yield. The 3,4-di-O-acetyl-6-O-p-toluenesulfonyl-D-glucal was converted to 3,4-di-O-acetyl-6-azido-6-deoxy-D-glucal using sodium azide. Reduction of the azide to 3,4-di-O-acetyl-6-amino-6-deoxy-D-glucal was achieved by either the Staudinger reaction or treatment with nickel boride. The 3,4-di-O-acetyl-6-amino-6-deoxy-D-glucal was found to rearrange to (1R)-(2-furyl)-2-acetamidoethanol under acidic conditions. The chiral furan was reacted with N-phenylmaleimide to form a crystalline Diels-Alder adduct the X-ray structure of which was determined. Acetylation of 3,4-di-O-acetyl-6-amino-6-deoxy-D-glucal yielded 6-acetamido-3,4-di-O-acetyl-6-deoxy-D-glucal. This compound was also synthesized from 3,4-di-O-acetyl-6-azido-6-deoxy-D-glucal by reduction with lithium aluminum hydride followed by acetylation, or by using thiolacetic acid as a reductive acylating agent. Treatment of 6-acetamido-3,4-di-O-acetyl-6-deoxy-D-glucal with palladium(II) chloride resulted in the formation of (4R)-acetoxy-7-acetyl-7-aza-2-oxabicyclo (3.2.1) oct-5-ene. Cleavage of 6-acetamido-3,4-di-O-acetyl-6-deoxy-D-glucal with ammonium nitrate and trifluoroacetic anhydride gave (E)-5-acetamido-(3S)-acetoxy-(4R)-formoxy-1-nitro-1-pentene. Intramolecular cyclization of this nitroalkene afforded a C-4 epimer of a precursor to ($-$) Anisomycin, (3S)-acetoxy-1-acetyl-(4R)-formoxy-(2R)-nitromethylpyrrolidine. Mercury catalyzed hydrolysis of 6-acetamido-3,4-di-O-acetyl-6-deoxy-D-glucal yielded 6-acetamido-4-O-acetyl-2,3,6-trideoxy-aldehydo-D-erythro-trans-hex-2-enose. Cleavage of 3,4-di-O-acetyl-L-rhamnal gave 4-O-acetyl-2,3,6-trideoxy-aldehydo-L-erythro-trans-hex-2-enose which was reacted with one equivalent of tosylhydrazine to give the $\alpha,\beta$-unsaturated tosylhydrazone. However, treatment of the 4-O-acetyl-2,3,6-trideoxy-aldehydo-L-erythro-trans-hex-2-enose with two equivalents of tosylhydrazine yielded a cyclic product, 4-O-acetyl-1,2,3,6-tetradeoxy-1-C-(2-p-toluenesulfonyl-hydrazino)-3-C-p-toluenesulfonyl-$\beta$-L-arabino-hexopyranose. The $\alpha,\beta$-unsaturated aldehyde obtained from 3,4-di-O-acetyl-L-rhamnal was acetylated to give 4,5-di-O-acetyl-2,3,6-trideoxy-aldehydo-L-erythro-trans-hex-2-enose. Reaction of this compound with excess tosylhydrazine yielded only (E)-(4R,5S)-diacetoxy-2-hexenal tosylhydrazone. Similar results were obtained in the D-glucose series. 3,4,6-Tri-O-acetyl-D-glucal was cleaved using aqueous mercuric sulfate to 4,6-di-O-acetyl-2,3-dideoxy-aldehydo-D-erythro-trans-hex-2-enose which was reacted with one equivalent of tosylhydrazine to give (E)-(4S),6-diacetoxy-(5R)-hydroxy-2-hexenal tosylhydrazone. The reaction of a second equivalent of tosylhydrazine with the mono-tosylhydrazone yielded the cyclized product 4,6-di-O-acetyl-1-C-(2-p-toluenesulfonylhydrazino)-3-C-p-toluenesulfonyl-1,2,3-trideoxy-$\beta$-D-arabino-hexopyranose. The $\alpha,\beta$-unsaturated aldehyde derived from 3,4,6-tri-O-acetyl-D-glucal was acetylated to give 4,5,6-tri-O-acetyl-2,3-dideoxy-aldehydo-D-erythro-trans-hex-2-enose. Treatment of this compound with an excess of tosylhydrazine yielded only (E)-(4S,5R),6-triacetoxy-2-hexenal tosylhydrazone and no cyclization product.
Language: English
Format: Degree Work