Synthesis of (-)-7-epiaustraline and (-)-1-epicastanospermine.
Highly efficient and selective syntheses of the title compounds are described. The cornerstone of the synthetic plan is the tandem inter [4 + 2]/inter [3 + 2] cycloaddition process. These syntheses differ from previous applications of this strategy in that they incorporate an alkylation in the hydrogenolysis step to close the second ring of the azabicyclic systems. Notable features of the sequence are (1) the highly regio- and stereoselective [3 + 2] cycloaddition of nitronate 15 with siloxymethyl (Z)-beta-silylvinyl ketone (Z)-22b and (2) the highly selective reduction of the resulting ketone 24a with L-Selectride. A single-crystal X-ray structure analysis of synthetic (-)-7-epiaustraline confirmed that the targeted structure was successfully synthesized. This stimulated a reexamination of the structural assignment of the natural product. (-)-1-Epicastanospermine was synthesized in four steps from the common intermediate 27a. The absolute configuration of (-)-1-epicastanospermine was assured by single-crystal X-ray structure analysis of intermediate (-)-27a. Thus, the sign of the optical rotation had to be revised. The overall efficiency of these syntheses were 9 steps and 23% yield for (-)-7-epiaustraline and 10 steps and 20% yield for (-)-1-epicastanospermine
Denmark
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SE
Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, Illinois 61801, USA.
Herbert
B
B
D000478:Alkylation; D018360:Crystallography, X-Ray; D003500:Cyclization; D006868:Hydrolysis; D007212:Indolizines / Q000138:chemical synthesis* / Q000737:chemistry; D009904:Optical Rotation; D010944:Plants / Q000737:chemistry*; D011763:Pyrrolizidine Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D012639:Seeds / Q000737:chemistry; D054836:Indolizidines
D007212:Indolizines; D011763:Pyrrolizidine Alkaloids; C412020:epiaustraline; C037806:castanospermine; D054836:Indolizidines