Isoquinoline alkaloids production

In this chapter, establishment of transformed cultures of P somniferum [24, 141] and isoquinoline alkaloid production by them under different cultural conditions [142, 143] are described. 

Isoquinoline alkaloid production by liquid culture of MAFF... 

Isoquinoline Alkaloids" Academic Press New York, 1972 (e) Kametani, T. In "The Total Synthesis of Natural Products" ApSimon, J., Ed. Wiley-... 

The high enantioselectivity of the exo product opens up a new and readily accessible route to an enantioselective synthesis of interesting isoquinoline alkaloids (Scheme 6.15) [35]. The tricyclic isoxazolidine exo-15b was obtained from the 1,3-dipolar cydoaddition reaction as the pure exo isomer and with 58% ee [34]. As shown in Scheme 6.15 the exo product from the 1,3-dipolar cydoaddition was converted into 17 in two steps without racemization at the chiral center. In addition to the illustrated synthesis, the 6,7-dimethoxy-derived isoxazolidine exo-15b is a very useful precursor for the synthesis of naturally occurring isoquinoline alkaloids [36-40]. 

Hydroxylation at C-5 or C-l3 has also been successfully achieved by lead tetraacetate oxidation, which was extensively studied in connection with isoquinoline alkaloids by Umezawa s group. (+)-Govanine (96) and (+)-discretine (97) were oxidized with lead tetraacetate in acetic acid to afford 5-acetoxy products 100,101, and 102 via p-quinol acetates (e.g., 99) (Scheme 23)... 

The 6,7-secoberbine alkaloids contain the four following natural products corydalic acid methyl ester (55), corydamine (56), N-formylcorydamine (57), and hypecumine (58). These bases, called 3-arylisoquinolines, were described by Shamma and Moniot (2) as a separate class of isoquinoline alkaloids. Santavy (7) classified them among benzophenanthridines. It seems, however, that they may be considered as biosynthetic intermediates between the protoberberines on the one hand and the benzophenanthridines on the other. 

The photocyclization of enamides to quinolines or isoquinolines has become an important reaction in the synthesis of alkaloids 219,358). It has recently been applied in the preparation of the isoquinoline alkaloid polycarpine 359). The principle of the reaction is demonstrated in the preparation of dihydroquinolines 360> (3.39) and of spirocyclohexaneisoquinoline derivatives (3.40) 361K In each case the electrocyclic ring closure product undergoes a subsequent 1,5-hydrogen shift. 

Baker BJ (1996) Carboline and isoquinoline alkaloids from marine organisms. In Pelletier SW (ed) Alkaloids chemical and biological perspectives, vol 10. Pergamon, Oxford, pp 357 107 Baldauf SL (2003) The deep roots of eukaryotes. Science 300 1703-1706 Blunt JW, Copp BR, Munro MHG, Northcote PT, Prinsep MR (2006) Marine natural products. Nat Prod Rep 23 26-78... 

Bentley, K. W. 2000. (3-Phenylethylamines and the isoquinoline alkaloids. Nature Product Reports, 17 247-268. 

Further extensions of the slilbene photocydizatinn are seen in analogous reactions of compounds containing the imine chro-mophore (e.g. 3,71 or an amide group (3.72). The amide reaction can be considered formally as giving a zwitterion intermediate, which undergoes proton shifts and oxidation to form the observed product. Non-oxidative cyclizations that start with either JV-vinyl aromatic carboxamides (C=C—N—CO—Ar) or N-aryl a. -unsaturated carboxamides (Ar—N—CO—C—C) have been extensively used to make quinoline or isoquinoline alkaloids and their derivatives a fairly simple example is given in (3.73). 

Benzylated 1,2,3,4-tetrahydroisoquinolines possess important physiological properties and, as illustrated in Scheme 20, also serve as common intermediates for synthesis of naturally ubiquitous isoquinoline alkaloids with different skeletons. Because some natural products have the 1/ configuration while the others possess the IS configuration, the synthesis must be chirally flexible. 

Asymmetric hydrogenation of Scheme 1.101 provides a general route to isoquinoline alkaloids (see Section 1.3.1.1). An imine substrate is hydrogenated with the chiral titanocene (/ )-34 to give the S product with 98% ee [346a,b,352], A neutral BCPM-Ir complex with phthalimide in toluene also shows high enantioselection [358]. The choice of a weakly polar... 

Abstract The multi-step enzyme catalysed biosyntheses of monoterpenoid indole and isoquinoline alkaloids are described. Special emphasis is placed on those pathways leading to alkaloids of pharmacological and medicinal significance which have been fully elucidated at the enzyme level. The successful identification and cloning of cDNAs of single enzymes and their application provides great opportunities to develop novel strategies for both in vitro and in vivo alkaloid production in whole plants or tissue cultures, as well as in microbial systems such as Escherichia coli and yeast. 

The isolation of the cDNAs encoding the enzymes involved in diverse isoquinoline alkaloid formation in plants and microorganisms allowed the first metabolic engineering routes to be developed and paved the way for new ways of future production of isoquinoline alkaloids. For instance, transgenic opium poppy plants were created in which codeinone reductase was suppressed by RNAi, resulting in the substitution of morphine synthesis with the non-narcotic precursor reticuline [110]. In a similar approach, RNAi suppression or overexpression of salutaridinol 1-0-acetyltransferase in opium poppy led to accumulation of salutaridine or increase of morphine, codeine and thebaine content [111], suppression of the BBE led to accumulation of berberine in California poppy cells [112],... 

Quinoline forms part of quinine (structure at the head of this chapter) and isoquinoline forms the central skeleton of the isoquinoline alkaloids, which we will discuss at some length in Chapter 51. In this chapter we need not say much about quinoline because it behaves rather as you would expect—its chemistry is a mixture of that of benzene and pyridine. Electrophilic substitution favours the benzene ring and nucleophilic substitution favours the pyridine ring. So nitration of quinoline gives two products—the 5-nitroquinolines and the 8-nitroquinolines—in about equal quantities (though you will realize that the reaction really occurs on protonated quinoline. 

Regioselective C- cleavage. When heated in ethyl chloroformate, tetra-hydroberberine (1) is cleaved to 2 as the only product (81% yield). The product was converted by known reactions into ( )-canadaline (3), representative of a new group of isoquinoline alkaloids, the secoberberines. ... 

Enantioselective hydrogenation of certain a- and 3-(acylamino)acrylic acids or esters in alcohols under 1-4 atm H2 affords the protected a- and 3-amino acids, respectively (eqs eq 3 and eq 4). Reaction of N-acylated 1-alkylidene-1,2,3,4-tetrahydroisoquinolines provides the IR- or 15-alkylated products. This method allows a general asymmetric synthesis of isoquinoline alkaloids (eq 5). ... 

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