Enantioefficient synthesis of alpha-ergocryptine: first direct synthesis of (+)-lysergic acid.
The first direct synthesis of (+)-lysergic acid (2a) suitable for scale-up has been achieved by the following reaction sequence. Bromoketones 4d or 4g were allowed to react with amine 5 followed by deprotection, and the resulting diketone 6c was transformed into the unsaturated ketone (+/-)-7 by the LiBr/Et(3)N system. Resolution afforded (+)-7, which was further transformed by Schöllkopf's method into the mixture of esters 2e and 2f. Upon hydrolysis the latter mixture afforded (+)-2a. The peptide part of alpha-ergocryptine (1) was prepared according to the Sandoz method; the stereoefficiency, however, has been significantly improved by applying a new resolution method and recycling the undesired enantiomer. Coupling the peptide part with lysergic acid afforded 1. Having synthetic (+)-7 in hand, we can claim the total synthesis of all the alkaloids which were prepared earlier from (+)-7 that had been obtained through degradation of natural lysergic acid.
Moldvai
István
I
Chemical Research Center, Institute of Biomolecular Chemistry, Hungarian Academy of Sciences, POB 17, H-1525 Budapest, Hungary.
Temesvári-Major
Eszter
E
Incze
Mária
M
Szentirmay
Eva
E
Gács-Baitz
Eszter
E
Szántay
Csaba
C
D002384:Catalysis; D004873:Ergolines / Q000138:chemical synthesis*; D007211:Indoles / Q000737:chemistry; D008237:Lysergic Acid / Q000138:chemical synthesis*; D015394:Molecular Structure; D013237:Stereoisomerism
D004873:Ergolines; D007211:Indoles; C100269:ergocryptine; D008237:Lysergic Acid