2.1.1.4
Ergopeptams
Ergopeptams are noncyclol lactam ergot alkaloids (LEA). Their structure is
similar to ergopeptines except that the amino acid III is d-proline and the
tripeptide chain is a noncyclol lactam (Fig. 5). The ergopeptams are further
classified as ergotamams, ergoxams, ergotoxams, and ergoannams [2, 7, 9].
Progress and Prospects of Ergot Alkaloid Research
5
Fig. 5. General structure of ergopeptams. (R 1 = substituent of amino acid I; R 2 = substituent of
amino acid II; amino acid III is d-proline)
Table 1. Overview of the research work done on the chemical synthesis of ergot alkaloids
Target
Strategy/reaction
Reference
(±)-Lysergic acid
Reductive photocyclization of the enamide, derived [12]
from a tricyclic ketone followed by ring opening
of the resulting dihydrofuran derivative
Racemic lysergene,
Reductive photocyclization of the furylenamide
[13]
agroclavine
followed by formation of the dihydrofuran ring;
final products were formed by ring opening
(±)-Elymoclavine,
Synthesis according to the synthetic route
[14]
(±)-isolysergol
involving enamide photocyclization
(±)-Isofumigaclavine B,
Reductive photocyclization of the enamide followed [15]
methyl(±)-lysergate,
by glycol formation and oxidative cleavage of the
methyl(±)-isolysergate
dihydrofuran ring
(±)-Agroclavine,
Reductive photocyclization of the enamide followed [16]
(±)-agroclavine I,
by glycol formation and oxidative cleavage of the
(±)-fumigaclavine B,
dihydrofuran ring
lysergene
2.1.2
Synthesis of Clavine Alkaloids and Lysergic Acid Derivatives
The ergoline nucleus has long been a challenging target for total synthesis with
attempts dating back to the classic work of Uhle in 1949 and culminating in the
synthesis of lysergic acid by Kornfeld and coworkers in 1954. The central intermediate in several successful syntheses, for example Ramage et al. in 1976, Nichols
et al. in 1977, and Kornfeld and Bach in 1971, has been Uhle’s ketone, either as the
protected derivative or its carbonyl transposition (for references see [10, 11]). The
total synthesis of ergot alkaloids has received increasing attention in the 1980s
and 1990s, is the focus of this section, and is presented in tabular form (Table 1).
Ergopeptams
Ergopeptams are noncyclol lactam ergot alkaloids (LEA). Their structure is
similar to ergopeptines except that the amino acid III is d-proline and the
tripeptide chain is a noncyclol lactam (Fig. 5). The ergopeptams are further
classified as ergotamams, ergoxams, ergotoxams, and ergoannams [2, 7, 9].
Progress and Prospects of Ergot Alkaloid Research
5
Fig. 5. General structure of ergopeptams. (R 1 = substituent of amino acid I; R 2 = substituent of
amino acid II; amino acid III is d-proline)
Table 1. Overview of the research work done on the chemical synthesis of ergot alkaloids
Target
Strategy/reaction
Reference
(±)-Lysergic acid
Reductive photocyclization of the enamide, derived [12]
from a tricyclic ketone followed by ring opening
of the resulting dihydrofuran derivative
Racemic lysergene,
Reductive photocyclization of the furylenamide
[13]
agroclavine
followed by formation of the dihydrofuran ring;
final products were formed by ring opening
(±)-Elymoclavine,
Synthesis according to the synthetic route
[14]
(±)-isolysergol
involving enamide photocyclization
(±)-Isofumigaclavine B,
Reductive photocyclization of the enamide followed [15]
methyl(±)-lysergate,
by glycol formation and oxidative cleavage of the
methyl(±)-isolysergate
dihydrofuran ring
(±)-Agroclavine,
Reductive photocyclization of the enamide followed [16]
(±)-agroclavine I,
by glycol formation and oxidative cleavage of the
(±)-fumigaclavine B,
dihydrofuran ring
lysergene
2.1.2
Synthesis of Clavine Alkaloids and Lysergic Acid Derivatives
The ergoline nucleus has long been a challenging target for total synthesis with
attempts dating back to the classic work of Uhle in 1949 and culminating in the
synthesis of lysergic acid by Kornfeld and coworkers in 1954. The central intermediate in several successful syntheses, for example Ramage et al. in 1976, Nichols
et al. in 1977, and Kornfeld and Bach in 1971, has been Uhle’s ketone, either as the
protected derivative or its carbonyl transposition (for references see [10, 11]). The
total synthesis of ergot alkaloids has received increasing attention in the 1980s
and 1990s, is the focus of this section, and is presented in tabular form (Table 1).