An efficient and enantioselective approach to the azaspirocyclic core of alkaloids: formal synthesis of halichlorine and pinnaic acid.
A novel, highly stereoselective synthesis of an azaspirocyclic core, which contains four stereogenic carbons consistent with structures of natural halichlorine and pinnaic acid, is presented. Lipase PS-catalyzed selective acylation, asymmetric methylation on the alpha-methylene of the bicyclic lactone, and an asymmetric Michael addition of the tertiary nitro cyclopentane were concisely used to conquer the challenging problem of successfully constructing the C9 quarternary carbon center with complete stereocontrol. The spiropiperidine ring was formed by reduction of the delta-nitroketone, intramolecular condensation, and then highly stereoselective reduction of the cyclic nitrone with NaBH(4). This spirocyclic core is a key intermediate in Danishefsky's synthesis of pinnaic acid and halichlorine.
Zhang
Hong-Lu
HL
Laboratory of Modern Organic Synthetic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, P.R. China.
Zhao
Gang
G
Ding
Yu
Y
Wu
Bin
B
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D007202:Indicators and Reagents; D015394:Molecular Structure; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000470:Alkaloids; D001372:Aza Compounds; D007202:Indicators and Reagents; D013141:Spiro Compounds; C412666:halichlorine; C412665:pinnaic acid