Enantioselective formal synthesis of (+)-dihydrocorynantheine and (-)-dihydrocorynantheol.
The enantioselective construction of the 3-ethylindolo[2,3-a]quinolizidine moiety present in numerous indole alkaloids is reported, the key steps being a stereoselective cyclocondensation of (S)-tryptophanol with an appropriate racemic delta-oxoester and a regio- and stereoselective cyclization of the resulting oxazolopiperidones on the lactam carbonyl group. A new procedure for the removal of the hydroxymethyl auxiliary group, involving oxidation to an aldehyde, dehydration of the corresponding oxime, and reductive decyanation of the resulting alpha-aminonitrile, has been developed. The preparation of indoloquinolizidine 27 represents a formal total synthesis of (+)-dihydrocorynantheine, (-)-dihydrocorynantheol, and other indolo[2,3-a]quinolizidine and oxindole alkaloids bearing the same substitution pattern.
Amat
Mercedes
M
Laboratory of Organic Chemistry, Faculty of Pharmacy, and Institute of Biomedicine, University of Barcelona, 08028-Barcelona, Spain. amat@ub.edu
Gómez-Esqué
Arantxa
A
Escolano
Carmen
C
Santos
Maria M M
MM
Molins
Elies
E
Bosch
Joan
J
D000470:Alkaloids / Q000138:chemical synthesis*; D003500:Cyclization; D007211:Indoles / Q000138:chemical synthesis; D010881:Piperidones / Q000138:chemical synthesis / Q000737:chemistry; D054837:Quinolizidines / Q000138:chemical synthesis; D013237:Stereoisomerism; D014364:Tryptophan / Q000031:analogs & derivatives / Q000737:chemistry
D000470:Alkaloids; D007211:Indoles; D010881:Piperidones; D054837:Quinolizidines; C007398:dihydrocorynantheol; C069544:tryptophanol; D014364:Tryptophan; C038369:hirsutine