Synthesis of 4-octuloses, V - 4-octulose derivatives as key intermediates in a new and short synthesis of polyhydroxyindolizidines

Reaction of 3 with (cyanomethylene)triphenylphosphorane in refluxing dichlo romethane or methanol gave mixtures of 4a and 4b in ratios of about 3:1 and 1:3, respectively. The same reaction performed with the furanoid isomer 5 afforded 6a and 6b in (E)/(Z) ratios of approximately 9:1 and 1:2, respecti vely. Catalytic hydrogenation of the alpha,beta-unsaturated nitriles 4 and 6 with either 10% Pd-C or Raney nickel afforded the saturated nitriles 7 an d 9, or the 1-amino-1,2,3-trideoxy-4-octulose derivatives 8 and 10, respect ively. In an attempt to transform 6a into the appropriate polyhydroxylated branched-chain pyrrolidine 15, (5R,8S,9R,10S)-8,9,10-trihydroxy-1-aza-6-oxa spiro[4.5]decane which was identified as its peracylated derivative 16, was isolated. Following an alternative synthetic strategy, partial hydrolysis of compound 9 afforded 17 which was regioselectively transformed into the c orresponding derivative 22 via its 8-O-p-toluenesulfonyl derivative 18. Rem oval of the 4,5-O-isopropylidene group in 22 with aqueous trifluroacetic ac id gave the free octulose 23, which was hydrogenated in the presence of 10% Pd-C, to afford the expected (6S,7R,8R,8aR)-6,7,8-trihydroxyindolizidine ( 1-deoxycastanospermine, 11).