Premium
4‐Octulose Derivatives as Key Intermediates in a New and Short Synthesis of Polyhydroxyindolizidines
Author(s) -
Izquierdo Isidoro,
Plaza María T.,
Robles Rafael,
Rodríguez Concepción,
Ramírez Antonio,
Mota Antonio J.
Publication year - 1999
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/(sici)1099-0690(199906)1999:6<1269::aid-ejoc1269>3.0.co;2-h
Subject(s) - chemistry , raney nickel , dichloromethane , hydrolysis , derivative (finance) , methanol , aqueous solution , organic chemistry , medicinal chemistry , pyrrolidine , catalytic hydrogenation , catalysis , solvent , financial economics , economics
Reaction of 3 with (cyanomethylene)triphenylphosphorane in refluxing dichloromethane 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, respectively. Catalytic hydrogenation of the α,β‐unsaturated nitriles 4 and 6 with either 10% Pd‐C or Raney nickel afforded the saturated nitriles 7 and 9 , or the 1‐amino‐1,2,3‐trideoxy‐4‐octulose derivatives 8 and 10 , respectively. In an attempt to transform 6a into the appropriate polyhydroxylated branched‐chain pyrrolidine 15 , (5 R ,8 S ,9 R ,10 S )‐8,9,10‐trihydroxy‐1‐aza‐6‐oxaspiro[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 corresponding derivative 22 via its 8‐ O ‐ p ‐toluenesulfonyl derivative 18 . Removal of the 4,5‐ O ‐isopropylidene group in 22 with aqueous trifluroacetic acid gave the free octulose 23 , which was hydrogenated in the presence of 10% Pd‐C, to afford the expected (6 S ,7 R ,8 R ,8 aR )‐6,7,8‐trihydroxyindolizidine (1‐deoxycasta‐nospermine, 11 ).