Synthesis of 4-octuloses, VI - 4-octulose derivatives, prepared from L-sorbose, as key intermediates in the stereoselective synthesis of C-glycoside and polyhydroxyindolizidine analogues

Reactions of 1 and 12 with p-toluenesulfonyl chloride in pyridine gave the corresponding 1-O-p-toluenesulfonyl derivatives 2 and 13 in yields of 91% a nd 60%, respectively, Compound 12 was also transformed into 14 by treatment with I-2/ Ph3P/imidazole in anhydrous dichloromethane. Treatment of compou nds 12 and 13/14 with NaN3 in DMF furnished the respective l-azido-l-deoxy derivatives 3 and 15, which were then deacetonated to give the free 4-octul oses 4 and 16. These were subsequently hydrogenated in the presence of 10% Pd/C to afford the expected polyhydroxylated branched-chain pyrrolidines 5 and 17. Attempted OH --> OMes transformation at C-8 in the N-Cbz-protected pyrrolidines 7 and 19 was unsuccessful and an internal anhydration process took place to yield the corresponding C-glycoside-like furanoses 9 and 20. On the other hand, 23 was transformed into the D-ribo analogue 25 through r eduction of the intermediate 4,6-diulose 24. Finally, deprotection of 25 in acid medium to give the free 4-ulose 26, followed by hydrogenation of the latter in the presence of 10% Pd/C in methanol, allowed the preparation of (6S,7S,8S,8aS)-6,7,8-trihydroxy-8a-methoxyindolizidin-3-one (27).