Formation of alkaloids

The Pictet-Spengler condensation has been of vital importance in the synthesis of numerous P-carboline and isoquinoline compounds in addition to its use in the formation of alkaloid natural products of complex structure. A tandem retro-aldol and Pictet-Spengler sequence was utilized in a concise and enantioselective synthesis of 18-pseudoyohimbone. Amine 49 cyclized under acidic conditions to give the condensation product 50 in good yield. Deprotection of the ketone produced the indole alkaloid 51. 

Singly bridged dimers resulting from C—C coupling had been produced by in vitro oxidation of benzylisoquinoline monomers, but this is the first report of their natural occurrence. Pisopowine-type dimers may be biogenetic intermediates in the formation of alkaloids of the funiferine (71) and tiliacorine (65) groups (566). 

During the last two decades, the use of enzyme-catalysed reactions in the total chemical synthesis and in the biological formation of alkaloids has been rapidly developed and a large number of enzymes and genes (cDNAs) involved in the biosynthesis of alkaloids have become available. 

When the Claviceps strain SD 58 was grown in a culture medium containing saccharose the slow formation of alkaloids containing polar groups was observed (15). These could not be extracted from the water phase in either alkaline or acid medium by the usual solvents. Finally, the principal alkaloid was isolated by ion exchange procedures and purified by subsequent chromatographic methods. The alkaloid was identified as elymoclavine-O-jS-D-fructofuranoside (12 ... 

Therefore, this review is mainly devoted to the application of electroorganic reactions to the synthesis of some key skeletons which are commonly found in natural alkaloids and some key intermediates which are useful materials for the formation of alkaloidal structures. The synthesis of some other nitrogen heterocycles which are usually not found in alkaloidal compounds will not be part of this review even though the structures are highly interesting as targets in organic synthesis. 

It has been concluded that formation of alkaloids such as tomatidine (140) and solasodine (141) occurs by amination of C-26-hydroxylated steroids [as (142)], formation of the furan ring being a subsequent step.122 Incorporation of (25-RS)-[25,26-3H2,4-14C]cholesterol (143) into tomatidine (140), soladulcidine (141 no 5,6-double bond), and solasodine (141) without change in isotope ratio is consistent with direct amination of an intermediate C-26/27-hydroxylated steroid, i.e. no C-26/27-oxo-intermediate is formed. Further, since tritium is not lost from C-25, the alkaloids (140) and (141), which are epimeric at this centre, must be formed... 

A key reaction in the formation of alkaloids involves the formation of C-N bonds between amines and aldehydes or ketones. The reaction involves nucleophilic addition followed by the elimination of water to give an imine or Schiff base. The protonated form of this imine is believed to act as an electrophile in a Mannich... 

Jaretzky Arch. Pharm. Berl. 273, 348 [1935]) reported the saprophytic culture of ergot on a suitable medium and claimed that the cornutine test (p-dimethylaminobenzaldehyde) and the biological test of Broom and Clark both gave positive results. The formation of alkaloids by Claviceps purpurea in saprophytic culture was also described by de Tempe (Thesis, Amsterdam 1945), but again a red coloration with van Urk s reagent was the only basis for this claim. 

A variety of methods have played important roles in determining the site of formation of alkaloids, and all are subject to serious experimental and interpretational errors. The culture of isolated organs can lead to erroneous interpretations and the analysis of sap currents (xylem and phloem) is fraught with obvious inherent difficulties. In grafts the shoot often forms adventitious roots which may not be visible when they grow into the stock. Such a graft is not only under the influence of the stock root but under its own, and very short roots can show very great alkaloid synthesis activity (244, 245). 

Benzodiazepine Aikaioids.—Benzodiazepine alkaloids, e.g. cyclopenin (123), are produced by Penicillium cyclopium. Their biosynthesis is pretty well understood. Recently, the production of enzymes involved in the biosynthesis and formation of alkaloid in relation to the development of the organism has been studied. The uptake of one of the precursors, i.e. phenylalanine, has also been studied. ... 

Facchini, in Chapter 1, reviews the significant studies that have been conducted with respect to how the formation of alkaloids in their various diverse sources are regulated at the molecular level. 

Isolation of Alkaloids Biosynthetic Origin of Alkaloids Some General Reactions Involved in the Formation of Alkaloids... 

Fig. 27.1. Amino acids commonly involved in the formation of alkaloids (Geissman and Crout, 1969).

These results suggest that the suppressed step for formation of alkaloids in sweet plants is the ring closure reaction from cadaverine to initial bicyclic and tetracyclic alkaloids, but neither the steps prior to the formation of cadaverine nor the specific reaction of cyclic alkaloids. 

Hayashi T, Yoshida K, Sano K (1988) Formation of alkaloids in suspension-cultured Colchi-cum autumnale. Phytochemistry 27 1371-1374... 

Iwasa K, Takao N (1982) Formation of alkaloids in Corydalis ophiocarpa callus culture. Phytochemistry 21 611-614... 

Plant tissue culture 1982.5th Int Congr Plant Cell CXilture, pp 315-316 Ikuta A, Syona K, Furuya T (1974) Alkaloids of callus tissues and redifferentiated plantlets in the Papaveraceae. Phytochemistry 13 2175-2179 Iwasa K. Takao N (1982) Formation of alkaloids in Corydalis ophiocarpa callus culture. Phytochemistry 21 611-614... 

Biosynthetic Formation of Alkaloids Derived from L-Ornithine... 

Formation of Alkaloids in Cell-Suspension Cultures.- This subject has been an active area of research in the last few years, and it is potentially a way to obtain economically useful natural products in a controlled environment, rather than by extracting whole plants, which are often difficult to cultivate in hospitable regions of our planet. Several books on this topic have appeared. The species Catharanthus roaeus has attracted much attention since it is a source of the clinically useful antitumor agents vinblastine and vincristine. Extensive work with this species has been carried out by Zenk ,Kutney ,Scott ,and their... 

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