82-58-6

Usage

Uses

Used in Pharmaceutical Industry:
9,10-DIDEHYDRO-6-METHYL-ERGOLINE-8-CARBOXYLIC ACID is used as a chemical intermediate for the synthesis of various ergot alkaloids and their derivatives, which have significant applications in the pharmaceutical industry. These alkaloids and their derivatives are known for their potent biological activities and are used in the development of drugs for treating various medical conditions.
Used as a Controlled Substance:
9,10-DIDEHYDRO-6-METHYL-ERGOLINE-8-CARBOXYLIC ACID is classified as a controlled substance due to its potential use in the illicit production of LSD, a potent hallucinogen and non-selective serotonin receptor agonist. The regulation and control of 9,10-DIDEHYDRO-6-METHYL-ERGOLINE-8-CARBOXYLIC ACID aim to prevent its misuse and ensure that it is only used for legitimate scientific and medical purposes.

Synthesis Reference(s)

Journal of the American Chemical Society, 78, p. 3087, 1956 DOI: 10.1021/ja01594a039

Flammability and Explosibility

Notclassified

Purification Methods

It crystallises from water as a hydrate. The methyl ester crystallises from C6H6 and has m 168o; the amide [478-94-4] has m 242o(dec) (from MeOH) and []546 +15o (c 0.5, pyridine).The (-)-hydrochloride has m 208-210o(dec, from MeOH). [Kornfeld et al. J Am Chem Soc 7 6 5256 1954,Kornfeld et al. J Am Chem Soc 78 3087 1956, Beilstein 25 III/IV 934,]

InChI:InChI=1/C16H16N2O2/c1-18-8-10(16(19)20)5-12-11-3-2-4-13-15(11)9(7-17-13)6-14(12)18/h2-5,7,10,14,17H,6,8H2,1H3,(H,19,20)/t10?,14-/m1/s1

Upstream product

• 421-20-5 Methyl fluorosulfonate 
• 7732-18-5 water 
• 478-95-5 6-methyl-9,10-didehydro-ergoline-8-carboxylic acid 
• 18698-97-0 ortho-bromophenylacetic acid 

Downstream Products

• 4579-64-0 lysergic acid methyl ester 
• 2126-78-5 lysergic acid diethylamide 
• 50-37-3 lysergide 
• 2481-70-1 ent-6-methyl-5α-ergoline-8β-carboxylic acid 
• 5878-43-3 9,10-dihydrolysergic acid 
• 479-00-5 ergonovinine 
• 60-79-7 ergometrine 
• 50868-53-6 (6aR,9S)-7-Methyl-4,6,6a,7,8,9-hexahydro-indolo[4,3-fg]quinoline-9-carboxylic acid [(S)-1-((S)-3-benzyl-1,4-dioxo-hexahydro-pyrrolo[1,2-a]pyrazine-2-carbonyl)-2-methyl-propyl]-amide 
• 50868-53-6 N-(d-Lysergyl-L-valyl)-L-phenylalanyl-D-prolin-lactam 
• 50868-53-6 (6aR,9S)-7-Methyl-4,6,6a,7,8,9-hexahydro-indolo[4,3-fg]quinoline-9-carboxylic acid [(S)-1-((S)-3-benzyl-1,4-dioxo-hexahydro-pyrrolo[1,2-a]pyrazine-2-carbonyl)-2-methyl-propyl]-amide 
• 50868-53-6 N-(d-Lysergyl-L-valyl)-L-phenylalanyl-L-prolin-lactam 
• 35121-60-9 10alpha-methoxy-9,10-dihydrolysergol 
• 23495-64-9 10α-methoxy-9,10-dihydrolysergic acid methylester 

Relevant academic research and scientific papers

Total synthesis of (+)-lysergic acid

A stereocontrolled total synthesis of (+)-lysergic acid (1) is achieved using three metal-catalyzed methodologies for the construction of three key rings. Highlights of the synthesis include Pd-catalyzed indole synthesis to form the B ring, a RCM reaction to form the D ring, and an intramolecular Heck reaction to form the C ring.

Total synthesis of (+)-lysergic acid

A total synthesis of (+)-lysergic acid, which features the C-C bond formation between C10 and C11 via cleavage of an aziridine ring, was accomplished.

Total synthesis of (+)-lysergic acid

We report the enantioselective total synthesis of (+)-lysergic acid using two different strategies, which featured three metal-catalyzed reactions for the construction of the BCD three rings, involving Pd-catalyzed indole synthesis for the construction of the B ring, a ring-closing metathesis reaction for the formation of the D ring, and an intramolecular Heck reaction to forge the C ring. In synthetic strategy I, the synthesis was achieved in 20 steps following the ring construction sequence of BDC. In synthetic strategy II, the synthetic route was shortened to only 12 steps by following the ring construction sequence of DBC and using a 4-chlorotryptophan derivative for the intramolecular Heck reaction. Moreover, we also discussed an unsuccessful synthetic strategy.

Total Synthesis of (+/-)-Lysergic Acid by an Intramolecular Imino-Diels-Alder Reaction

(+/-)-Lysergic acid (1) has been synthesized from 4-hydroxymethyl-1-tosylindole (2) by a sequence of 9 steps.The crucial thermolysis 9 ---> 10 involves the in situ-generation of the transient diene III which undergoes an intramolecular cycloaddition to a C,N-double bond at 200 deg C and at low stationary concentration of III.

New method for preparing lysergic acid through hydrolyzing

The invention discloses a new method for preparing lysergic acid through hydrolyzing. The method comprises the following steps: directly hydrolyzing ergometrine or ergometrinine with metal hydroxide to obtain lysergic acid. The method provided by the invention is safe, economical and suitable for industrial production, and the obtained lysergic acid is high in purity. Particularly, ergometrine or ergometrinine is hydrolyzed by metal hydroxide under the condition of heating, the purity requirements of the raw materials are low, the large-scale production is facilitated, and the raw material extraction and purification costs are reduced.

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.

PROCESS FOR THE MANUFACTURE OF LYSERGIC ACID

Lysergic acid is formed in high yields and high quality by isomerizing paspalic acid in a phase separated mixture formed by paspalic acid and a concentrated aqueous metal hydroxide solution.

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.