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Separation of four isomers of lysergic acid α-hydroxyethylamide by liquid chromatography and their spectroscopic identification. Flieger, M., Sedmera, P., Vokoun, J., R̆ic̄icovā, A., R̆ehác̆ek, Z. 1982. Journal of Chromatography A, 236(2), p. 441, doi: 10.1016/S0021-9673(00)84895-5
1. Spontaneous Decomposition
• The introduction notes that LAH "decomposes spontaneously" during fermentation production, resulting in a mixture containing ergine and erginine. This indicates that LAH is chemically unstable under typical fermentation conditions, leading to breakdown products.
2. Formation of Isomerization Products
• LAH undergoes isomerization, producing C(8) and C(9') epimers. The document mentions that these isomerization products are also formed when heating ergotamine or other cyclol alkaloids with dilute acid, suggesting that LAH's instability is exacerbated by heat and acidic conditions.
3. Complex Isomerization
• In the discussion section, the study explains that LAH isomerization is more complex than simple lysergic acid derivatives due to epimerization at both the C(8) position and the asymmetric carbon atoms in the side-chain. This results in four isomers (I, II, III, IV), which are hemiacetals derived from acetaldehyde and ergine or erginine.
• The reversible aldolization reaction contributes to LAH's instability, as evidenced by the mutual transformation of isomers (e.g., I to IV) observed during a 15-hour ¹³C NMR measurement, where signals of both C₁ atoms appeared.
4. Equilibrium in Fermentation
• The relative proportions of LAH isomers (I, II, III, IV), ergine (V), and erginine (VI) in the fermentation medium are described as the result of chemical equilibrium reactions, further highlighting LAH's tendency to interconvert and decompose under fermentation conditions.
5. Experimental Precautions
• Due to LAH's instability, the study took specific measures during extraction and chromatography to minimize structural changes:
• Extraction was performed at low temperatures (below 15°C) under reduced pressure.
• Chromatographic fractions were immediately evaporated to dryness at 5–10°C to prevent isomerization or degradation.
• These precautions underscore the need to handle LAH carefully to preserve its structure during analysis.
6. Artifact Formation
• The study confirms that ergine and erginine are likely "artifacts" arising from LAH decomposition, as observed during isomerization experiments. This supports the notion that LAH's instability leads to the formation of these compounds under various conditions.
In summary, the document details LAH's instability by describing its spontaneous decomposition into ergine and erginine, its complex isomerization involving C(8) and side-chain epimerization, and the equilibrium-driven transformations observed in fermentation and experimental conditions. The study also highlights practical measures to mitigate instability during analysis, emphasizing the compound's sensitivity to temperature, pH, and time.
Separation of four isomers of lysergic acid α-hydroxyethylamide by liquid chromatography and their spectroscopic identification. Flieger, M., Sedmera, P., Vokoun, J., R̆ic̄icovā, A., R̆ehác̆ek, Z. 1982. Journal of Chromatography A, 236(2), p. 441, doi: 10.1016/S0021-9673(00)84895-5
1. Spontaneous Decomposition
• The introduction notes that LAH "decomposes spontaneously" during fermentation production, resulting in a mixture containing ergine and erginine. This indicates that LAH is chemically unstable under typical fermentation conditions, leading to breakdown products.
2. Formation of Isomerization Products
• LAH undergoes isomerization, producing C(8) and C(9') epimers. The document mentions that these isomerization products are also formed when heating ergotamine or other cyclol alkaloids with dilute acid, suggesting that LAH's instability is exacerbated by heat and acidic conditions.
3. Complex Isomerization
• In the discussion section, the study explains that LAH isomerization is more complex than simple lysergic acid derivatives due to epimerization at both the C(8) position and the asymmetric carbon atoms in the side-chain. This results in four isomers (I, II, III, IV), which are hemiacetals derived from acetaldehyde and ergine or erginine.
• The reversible aldolization reaction contributes to LAH's instability, as evidenced by the mutual transformation of isomers (e.g., I to IV) observed during a 15-hour ¹³C NMR measurement, where signals of both C₁ atoms appeared.
4. Equilibrium in Fermentation
• The relative proportions of LAH isomers (I, II, III, IV), ergine (V), and erginine (VI) in the fermentation medium are described as the result of chemical equilibrium reactions, further highlighting LAH's tendency to interconvert and decompose under fermentation conditions.
5. Experimental Precautions
• Due to LAH's instability, the study took specific measures during extraction and chromatography to minimize structural changes:
• Extraction was performed at low temperatures (below 15°C) under reduced pressure.
• Chromatographic fractions were immediately evaporated to dryness at 5–10°C to prevent isomerization or degradation.
• These precautions underscore the need to handle LAH carefully to preserve its structure during analysis.
6. Artifact Formation
• The study confirms that ergine and erginine are likely "artifacts" arising from LAH decomposition, as observed during isomerization experiments. This supports the notion that LAH's instability leads to the formation of these compounds under various conditions.
In summary, the document details LAH's instability by describing its spontaneous decomposition into ergine and erginine, its complex isomerization involving C(8) and side-chain epimerization, and the equilibrium-driven transformations observed in fermentation and experimental conditions. The study also highlights practical measures to mitigate instability during analysis, emphasizing the compound's sensitivity to temperature, pH, and time.