Synthesis of 4‐Octuloses. Part 6. 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% and 60%, respectively. Compound 12 was also transformed into 14 by treatment with I2/ Ph3P/imidazole in anhydrous dichloromethane. Treatment of compounds 12 and 13/14 with NaN3 in DMF furnished the respective 1-azido-1-deoxy derivatives 3 and 15, which were then deacetonated to give the free 4-octuloses 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 R
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% and 60%, respectively. Compound 12 was also transformed into 14 by treatment with I2/Ph3P/imidazole in anhydrous dichloromethane. Treatment of compounds 12 and 13/14 with NaN3 in DMF furnished the respective 1-azido-1-deoxy derivatives 3 and 15, which were then deacetonated to give the free 4-octuloses 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 reduction 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).
A new and highly stereoselective synthesis of polyhydroxyindolizidines from 4-octulose derivatives
Abstract (1 S ,2 S ,6 R ,7 R ,8 R ,8a R )-1,2,6,7,8-Pentahydroxyindolizidine 12 and (1 R ,6 R ,7 R ,8 R ,8a R )-1,6,7,8-tetrahydroxyindolizidine (1,6-diepicastanospermine, 24 ) have been stereoselectively synthesized from the important key intermediates l,4-dideoxy-1,4-imino- d - erythro - l - altro -octitol 7 and 1,2,4-trideoxy-1,4-imino- d - glycero - d - talo -octitol 20 in three steps. Compounds 7 and 20 were readily obtained from 2,3:4,5:6,7-tri- O -isopropylidene-β- d - glycero - d - galacto -oct-4-ulo-4,8-pyranose 1 and 2-deoxy-4,5:6,7-di- O -isopropylidene-β- d - manno -oct-4-ulo-4,8-pyranose 13 in four steps, respectively.