Biosynthesis scheme

Epoxide ring-opening with transfer of an sp carbon moiety was applied in a short synthesis [44] of eicosanoid 56 [45], relevant in marine prostanoid biosynthesis (Scheme 9.13). Homoallyl alcohol 55 was obtained in good yield from 54 by use of a cyano-Gilman alkenylcuprate [46]. 

Several hypotheses have been proposed for the biogenesis of carbazole alkaloids (see Chapter 3 of this review). However, there is no deep experimental knowledge of the biosynthesis of this class of alkaloids. A comparison of the structural features of carbazole alkaloids isolated from higher plants suggests that 3-methylcarbazole (2) may represent the key intermediate in their biosynthesis (Scheme 1.1). 

Sugar methylation is the last step during REB biosynthesis (Scheme 20.2). A rebM-disrupted mutant of Lech, aerocolonigenes accumulated 4 -0-demethyl-REB (17),... 

Thus from an analysis of the biosynthetic gene clusters as well as from earlier biosynthetic studies (often with blocked mutants), it is useful to divide the poly-ketide biosynthetic pathway into PKS reactions and post-PKS tailoring steps. Several of the latter were investigated with respect to biosyntheses of angucy-clin(on)es and natural products derived thereof. Intensive studies of various blocked mutant products of Streptomyces fradiae Til 2717 resulted in a well established sequence of the late steps of urdamycin A (281) biosynthesis (Scheme 63) [164]. 

The steps of prenylation and dehydrogenation which follow (94) in the biosynthesis of these neoechinulins is unknown but from knowledge of echinulin biosynthesis (Scheme 6) introduction of the side chain at C-2 may be the next step. Prenylation of the benzene unit seems, by inspection of structures (97) through (101), to depend on C-8—C-9 unsaturation rather than the structure of the dioxo-piperazine ring. The stereochemistry of the desaturation reaction has been explored with L-tryptophan (85) samples stereospecifically labelled with tritium at... 

Austin (89) is clearly biosynthetically related to andibenin B and is formed from the same key intermediate (86). An interesting possibility was that the tetracyclic intermediate (91) involved in austin biosynthesis (Scheme 24) is not formed directly from cyclisation of (86) but is formed via the same bicyclo-farnesyl intermediate (87) involved in andibenin biosynthesis (Scheme 22). To test this, [6- C, 6-2H3]mevalonate was fed to 5-day old cultures and the resultant enriched austin isolated and its H, noise decoupled nmr spectrum determined. This showed clear isotopically shifted signals corresponding to the incorporation of two and mainly three deuteriums into the 12-, 13- and 14-methyl groups. The result for the 12-methyl group excludes the possibility of the involvement of (87) in austin biosynthesis. 

The alkaloids Af-methylpelletierine (90) and pseudopelletierine (91) of Punica granatum and also anaferine (92) of Withania somnifera are probably related in biosynthesis to sedamine and anabasine. The proposed biosynthesis (Scheme 17) has received support from recent tracer studies.57... 

The mechanism of cyclopentane ring formation of allosamizoline may take place via pathway A or B during inositol biosynthesis, whereas via pathway C during shikimic acid biosynthesis (Scheme 1). This was based on a study using [3- H]-, [4- H]-, [5- H]-and [6- H2]-D-glucosamine feeding in experiments which indicated that the cyclization to form the cyclopentanoid moiety of allosamizoline is presumed to proceed via a 4-keto or... 

Another concept that should be considered at this point is sequential blockade as it relates to chemotherapy. Considering the outline of the folate biosynthesis scheme (Fig. 7-8), the likelihood that the blockade with selective agents of more than one reaction in sequence will increase the therapeutic value of treatment is apparent. 

After pantothenate biosynthesis (Scheme 1) or uptake, the CoA biosynthetic pathway universally consists of five enzymatic steps as shown in Scheme 2. In the following sections, our current knowledge of each of the biosynthetic steps and other aspects of CoA biosynthesis will be highlighted with a special emphasis on their mechanism and structure. The diversity of genomic variations in the CoA pathway will also be discussed. Many excellent reviews on the CoA biosynthetic pathway have appeared in recent years. These differ in focus, and the readers are encouraged to refer to them as a complement to the content of this chapter whether their interest is... 

The NMR spectroscopy, mass spectrometry, and the biosynthesis (Scheme 2) of the tetrahydroprotoberberine alkaloids were described in detail in The Alkaloids, Vol. IX, Chapter 2 and in various publications... 

The stereochemistry of the last step in nicotine biosynthesis (Scheme 1) follows from the known stereochemistry of the alkaloid. It has been found that treating callus of Nicotiana tabacum... 

The microbial glycosidation of (8S)-8-fluoro erythronolides were investigated by the same research group. Fluorinated erythronolides A (46) and B (47) were added into the fermentation broth of Streptomyces erythraeus ATCC 31772, a blocked mutant in EM biosynthesis (Scheme 6). In this procedure, (85 )-8-fluoro... 

Bearing these taxonomic conclusions in mind, an overview of likely biosynthetic relationships between the isoflavonoids discussed in this chapter was proposed [6] and is represented in Fig. (4). This emphasises those compounds whose occurrence is restricted to the 3 species in the proposed series Pinnatifida (C. bijugum, C. judaicum and C. pinnatifidum) and attempted to address the biosynthesis of these compounds, most notably arybenzofurans which are still missing from the latest versions of the isoflavonoid biosynthesis schemes because of the lack of persuasive biogenetic evidence. A 2 -hydroxyisoflavanol, the immediate precursor of isoflav-3-enes and pterocarpans, is shown as the first intermediate. Its... 

FR901483 in suppressing the immune system results from an antimetabolite activity whereby adenylosuccinate synthetase and/or adenylosuccinate lyase are inhibited. These enzymes function as key catalysts in the de novo purine nucleotide biosynthetic pathway. Addition of adenosine or deoxyadenosine (but not deoxyguanosine, deoxycytidine, uridine or thymidine) results in elimination of the immunosuppressive activity of FR901483. Thus, FR901483 may inhibit one of the key steps for adenosine biosynthesis (Scheme 1). 

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