4579-64-0

Upstream product

• 186581-53-3 diazomethane 
• 82-58-6 D-lysergic acid 
• 67-56-1 methanol 
• 51867-18-6 (+)-9,10-didehydro-6-methylergoline-8-one 
• 253191-72-9 1-pivaloyl-4-bromo-5-oxo-1,3,4,5-tetrahydrobenz[c,d]indole 
• 1449117-86-5 (S,E)-4-bromo-3-(4-((tert-butyldimethylsilyl)oxy)pent-2-en-1-yl)-1H-indole 
• 52488-36-5 4-bromo-1H-indole 
• 181271-32-9 4-bromo-1-(4-toluenesulfonyl)indole-3-carboxaldehyde 
• 50-00-0 formaldehyd 
• 87332-72-7 C₁₆H₁₆N₂O₂ 
• 1159774-78-3 (6aR)-4,7-di-tert-butyl 9-methyl 6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-4,7,9-tricarboxylate 
• 1159774-77-2 (6aR,10aS)-4,7-di-tert-butyl 9-methyl 6,6a-dihydroindolo[4,3-fg]quinoline-4,7,9(8H,10aH)-tricarboxylate 
• 1449118-02-8 (6aR,10aS)-di-tert-butyl 9-formyl-6,6a-dihydroindolo[4,3-fg]quinoline-4,7(8H,10aH)-dicarboxylate 
• 1449117-98-9 (6aR,10aS)-di-tert-butyl 9-((S)-1,2-dihydroxyethyl)-6,6a-dihydroindolo[4,3-fg]quinoline-4,7(8H,10aH)-dicarboxylate 

Downstream Products

• 16727-34-7 (5R,8R)-6-methyl-8β-hydroxymethyl-9α-hydroxyergoline 
• 30334-04-4 6-cyano-9,10-didehydro-ergoline-8-carboxylic acid methyl ester 
• 5256-60-0 (+/-)-lysergic acid hydrazide 
• 916306-10-0 (6aR,9R)-9-(pyrrolidine-1-carbonyl)-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-7-carboxylic acid phenylamide 
• 916306-96-2 (6aR,9R)-7-phenylcarbamoyl-4,6,6a,7,8,9-hexahydro-indolo[4,3-fg]quinoline-9-carboxylic acid 
• 916306-95-1 (6aR,9R)-7-phenylcarbamoyl-4,6,6a,7,8,9-hexahydro-indolo[4,3-fg]quinoline-9-carboxylic acid methyl ester 
• 916306-98-4 toluene-4-sulfonic acid 2-[(6aR,9R)-7-phenylcarbamoyl-9-(pyrrolidine-1-carbonyl)-6a,7,8,9-tetrahydro-6H-indolo[4,3-fg]quinolin-4-yl]-ethyl ester 

Relevant academic research and scientific papers

Dimerization of (+)-lysergic acid esters

Dimer isomer mixtures, characterized by a bridgehead C8-C8′ bond, (6a-7a; 6b-7b) were obtained from (+)-lysergic acid methyl or ethyl ester (1b; 1c) in a solution of methanol or ethanol. The isomers were separated, and their structures were determined by detailed NMR measurements and X-ray analysis. Density functional theory was applied to provide insight into the reaction mechanism. Based on an extended examination and the theoretical calculations, a plausible reaction sequence leading to dimers is also presented. The proposed mechanism has been verified by detecting the formation of the superoxide radical anion (O2·-).

Total synthesis of lysergic acid

A total synthesis of lysergic acid was accomplished. Key features of our synthesis include stereoselective construction of the stereogenic centers at the allylic positions by using the Evans aldol reaction, and a sequential process with a ring-closing metathesis and an intramolecular Heck reaction to construct the C and D rings.

Enantioselective total synthesis of (+)-lysergic acid, (+)-lysergol, and (+)-isolysergol by palladium-catalyzed domino cyclization of allenes bearing amino and bromoindolyl groups

Enantioselective total synthesis of the biologically important indole alkaloids (+)-lysergol, (+)-isolysergol, and (+)-lysergic acid is described. Key features of these total synthesis include (1) a facile synthesis of a chiral 1,3-amino alcohol via the Pd(0)- and In(I)-mediated reductive coupling reaction between l-serine-derived 2-ethynylaziridine and formaldehyde; (2) the Cr(II)/Ni(0)-mediated Nozaki-Hiyama-Kishi (NHK) reaction of an indole-3-acetaldehyde with iodoalkyne; and (3) Pd(0)-catalyzed domino cyclization of an allene bearing amino and bromoindolyl groups. This domino cyclization enabled direct construction of the C/D ring system of the ergot alkaloids skeleton, as well as the creation of the C5 stereogenic center with transfer of the allenic axial chirality to the central chirality.

Enantioefficient synthesis of α-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/Et3N system. Resolution afforded (+)-7, which was further transformed by Schoellkopfs method into the mixture of esters 2e and 2f. Upon hydrolysis the latter mixture afforded (+)-2a. The peptide part of α-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.

Process for the preparation of lysergic acid esters

A process for preparing lysergic acid esters of the formula STR1 wherein R is alkyl of up to 3 carbon atoms, comprises reacting corresponding lysergic acid or isolysergic acid amides with corresponding alcohols at temperatures of 0° to 65° C. for 2 to 30 hours in the presence of an acid at a pH value of 0-1.