Norlaudanosoline

Nori (laver), common and scientific names, 3 188t Norit, 4 741 Norlaudanosoline, 2 87 Normal coarse grade Bayer alumina hydrate, 2 428... 

Aerial oxidation of norlaudanosoline in aqueous alkali and acetylation of the product affords the benzopyrrocoline (21), together with a dimer that is linked... 

The three cDNAs of norcoclaurine-6-O-methyltransferase, coclaurine-AA methyltransferase and 3 -hydroxy-AAmethylcoclaurine 4,-<9-methyltransferase converting (R, S)-norlaudanosoline into (R, Sj-reticuline with a 5-10% yield... 

About 20 mg salutaridine was formed from 4 mM norlaudanosoline in strain 1 which additionally expressed a human cytochrome P450 reductase... 

Moreover, transgenic yeast cells formed (S)-tetrahydroberberine ( 30 mg/L) amounting to a 1 -2% total conversion of norlaudanosoline in the seven-step pathway, and demonstrating the efficiency of the system, which most probably can be further optimised in future [123],... 

Norlaudanosoline [166) R = H] has for a long time been regarded, in schematic terms, as the biogenetic precursor of the isoquinoline alkaloids, and since it is now known158 that noradrenaline [(167) R = OH] is incorporated into berberastine (168) in Hydrastis canadensis L., presumably via 4-hydroxynorlaudanosoline [(166) R = OH], it is possible159 that a series of alkaloids exists based on 166 (R = OH) as parent. It is significant in this context that the alkaloids imenine... 

It is known that berberine (46) and the protoberberine alkaloid (S)-stylopine (44) are elaborated from an intact molecule of (S)-reticuline [as (33)], the 7V-methyl group providing C-8 in each alkaloid1,2,42 (cf. Vol. 7, p. 12). Exactly similar findings were obtained for tetrahydropalmatine (45) and palmatine (47) in C. laurifolius.43 Of several benzylisoquinolines tested, only reticuline (33), nor-reticuline (41), and norlaudanosoline (40) were significantly incorporated. Tetrahydropalmatine (45) was found to be converted into palmatine (47) and the conversion was irreversible. 

Gene regulation represents the most basic level of metabolic control. Although there are few examples in the alkaloid literature, the post-translational regulation of enzymes can also exert considerable influence over the control of metabolic flux. Recent work in our laboratory suggests that enzymatic controls function of the regulation in alkaloid biosynthesis. (5)-Norcoclaurine is accepted as the central precursor to all BAs produced in plants.6,7 However, NCS was first isolated based on its ability to convert dopamine and 3,4-dihydroxyphenylacetaldehyde (3,4-DHPAA) to the tetrahydroxylated alkaloid (S)-norlaudanosoline.129 The ability of NCS to accept either 4-HPAA or 3,4-DHPAA contributed to the incorrect conclusion that (S)-norlaudanosoline is a common pathway intermediate. However, only (5)-norcoclaurine has been detected in plants. 

Product inhibition kinetics performed at saturating levels of one substrate with norlaudanosoline as the inhibitor showed that NCS follows an iso-ordered biuni mechanism with 4-HPAA binding before dopamine (Fig.7.8). These data also imply that 4-HPAA combines with a form of the enzyme different from the alkaloid product since the inhibitor and first substrate do not bind competitively. After the product is released, NCS appears to undergo a conformational change reverting back to a form to which 4-HPAA can bind before another reaction sequence can begin.131... 

RUEFFER, M., EL-SHAGI, H., NAGAHURA, N ZENK, M.H., (S)-Norlaudanosoline synthase The first enzyme in the benzylisoquinoline biosynthetic pathway. FEBSLett., 1981,129, 5-9. 

SCHUMACHER, H.-M., RUFFER, M., NAGAKURA, N ZENK, M.H., Partial purification and properties of (5)-norlaudanosoline synthase from Eschscholtzia tenuifolia cell cultures. Planta Med., 1983, 48,212-220. 

We mentioned isoboldine a while back, so there must be a boldine as well. This alkaloid is also formed from norlaudanosoline by a different methylation sequence and oxidative radical coupling. Looking at the structure of boldine you may see what appears to be a mistake on someone s part. 

These hypotheses, although not always correct, have been of inestimable value in guiding tracer experiments on living plants. Experiments on the biosynthesis of berberine and related alkaloids have had, in addition to these guidelines, the benefit of the knowledge gained from previous tracer studies on the biosynthesis of the isoquinoline alkaloids of the papaverine and the morphine series, where it was known that two molecules of the aromatic amino acid, tyrosine, are built into these alkaloids via a pathway involving the intermediacy of norlaudanosoline (XCIV). 

The foregoing results are in consonance with the ideas proposed many years ago by Robinson and others, and are best interpreted as tyrosine giving rise to 3,4-dihydroxy-2-phenylethylamine and 3,4-dihydroxy-phenylacetaldehyde which condense to form the 1-benzylisoquinoline intermediate, norlaudanosoline. Insertion of the C-1 unit of the berberine bridge would then complete the skeleton of the protoberberine alkaloids. 

Although it is doubtful whether the number of alkaloids derived from 4-hydroxynorlaudanosoline will approach those biosynthesized via norlaudanosoline, some indications are becoming available that the former group will expand in the near future. Of the three new minor alkaloids in H. canadensis, whose presence was first revealed by the selective incorporation of labeled noradrenaline, one has been identified as a 5-hydroxytetrahydroberberine (CV) by virtue of its identity with the reduction product of berberastine (59). 

Treatment of cell suspension cultures of T. rugosum with a yeast glucan elicitor induced the production of tyrosine decarboxylase in the late exponential and early stationary growth phases of the cells. Tyrosine decarboxylase has been suggested as the key enzyme between primary and secondary metabolism in the biosynthesis of norlaudanosoline-derived alkaloids, and a good correlation between induced tyrosine decarboxylase activity and berberine biosynthesis has been established [163]. 

The finding that the majority of the Papaveraceae alkaloids arise from the benzylisoquinoline precursors reticulme, orientaline, and probably norlaudanosoline, by phenolic oxidation 30, 40,137,148, 35S), has... 

The biosynthesis of aporphine alkaloids takes the course—laudanoso-line, norlaudanosoline, reticuline, or orientaline—by means of phenolic oxidation via the cyclohexadienone proaporphine (27, 28, 39, 40, 47, 49, 65, 66, 68, 69,147,148,150, 229, 231, 240, 250, 275, 349, 445, 451, 512) after dienone-phenol or dienol-benzene rearrangement, as described in more detail in the preceding section. The foregoing results, considered as a whole (39,49), provide good evidence that isothebaine is biosynthesized in P. orientale along the following pathway ... 

Experiments carried out with labeled compounds did not prove conclusively that orientaline and norlaudanosoline (51) were the precursors of morphinane bases. 

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