NATURAL PRODUCTS. BIOSYNTHESIS

Kopp, F. and Marahiel, M.A. (2007) Macrocyclization strategies in polyketide and nonribosomal peptide biosynthesis. Natural Product Reports, 24, 735. 

Thiericke, R. and Rohr, J. (1993) Biological variation of microbial metabolites by precursor-directed biosynthesis. Natural Product Reports, 10 (3), 265-289. 

Keywords Amaryllidaceae alkaloid plant secondary metabolism alkaloid biosynthesis natural products systems biology galanthamine... 

Section 16 14 Epoxide functions are present m a great many natural products and epox ide ring opening is sometimes a key step m the biosynthesis of other sub stances... 

Isotope incorporation experiments have demonstrated the essential correctness of the scheme presented m this and preceding sections for terpene biosynthesis Considerable effort has been expended toward its detailed elaboration because of the common biosyn thetic origin of terpenes and another class of acetate derived natural products the steroids... 

Generally, the most powerful method for stmctural elucidation of steroids is nuclear magnetic resonance (nmr) spectroscopy. There are several classical reviews on the one-dimensional (1-D) proton H-nmr spectroscopy of steroids (267). C-nmr, a technique used to observe individual carbons, is used for stmcture elucidation of steroids. In addition, C-nmr is used for biosynthesis experiments with C-enriched precursors (268). The availability of higher magnetic field instmments coupled with the arrival of 1-D and two-dimensional (2-D) techniques such as DEPT, COSY, NOESY, 2-D J-resolved, HOHAHA, etc, have provided powerful new tools for the stmctural elucidation of complex natural products including steroids (269). 

Garbapenem P-Lactamase Inhibitors. Carbapenems are another class of natural product P-lactamase inhibitors discovered about the same time as clavulanic acid. Over forty naturally occurring carbapenems have been identified many are potent P-lactamase inhibitors. Garbapenem is the trivial name for the l-a2abicyclo[3.2.0]hept-2-ene ring system (21) shown in Table 3. The synthesis (74), biosynthesis (75), and P-lactamase inhibitory properties (13,14,66) of carbapenems have been reviewed. Carbapenems are often more potent than clavulanic acid and include type I Cephases in the spectmm of inhibition. Table 3 Hsts the available P-lactamase inhibition data. Synergy is frequendy difficult to demonstrate because the compounds are often potent antibacterials. 

Natural products biosynthesis, 1, 83-109 fused oxirane rings, 7, 192 fused thiirane rings, 7, 192-193 as insecticides, 1, 198 nomenclature, 1, 28-31 oxiranes, 7, 120 as pharmaceuticals, 1, I46-I56 pyridine derivatives... 

Pseudopterosin A is a member of a group of marine natural products which show potent antiinflammatory properties, but which are not prostaglandin biosynthesis inhibitors. Structurally similar to phosphatidyl inositol, they may function as phospholipase inhibitors, and, as such, may be the forerunners of a new class of therapeutic agents. 

In the first of these, the key step in the synthetic sequence involves an oxidative phenol coupling reaction patterned after the biosynthesis of the natural product. Preparation of the moiety that is to become the aromatic ring starts by methyla-tion of phloroglucinol (5) with methanolic hydrogen chloride to give the dimethyl ether (6). Treatment of that intermediate with sulfuryl chloride introduces the chlorine atom needed in the final product (7). 

Natural product synthesis poses the challenge to consider and develop new pathways of structural transformation. Natural products as targets for synthetic research possess a special fertility in this regard, because the structural channels of biosynthesis are not necessarily the conduits of organic synthesis. A. Eschenmoser19... 

The enzymatic conversion of a-(aminomethyl)pyrroles is also used by nature to produce porphyrinogens like uroporphyrinogen III (see introduction, compound 8), which is the key building block in the biosynthesis of all known porphinoid natural products. This biomimetic method is a powerful tool for the synthesis of different porphyrins, e.g. for the preparation of JV,Af, V ,Ar"-tetramethylporphyrin-2,3,7,8,12,13,17,18-octaacetic acid dibromide 12.36... 

Cytochrome P450 enzymes have been the subject of a number of recent reviews in which their mechanism and scope of action are covered in much detail [1, 6, 10, 11]. The reader is referred to these articles for a more thorough account of the mechanism and reactivity of cytochrome P450 enzymes, while we present a few representative examples of cytochrome P450-catalyzed epoxidation below. The enzymes we chose are all involved in the biosynthesis of polyketide natural products. Polyketides are a large, structurally diverse family of compounds and have provided a wealth of therapeutically useful drugs and drug leads. 

Aziridine Natural Products - Discovery, Biological Activity and Biosynthesis... 

One example of a naturally occurring diazirine, duazomycin A (137 Scheme 11.20), has been reported, isolated in 1985 from a Streptomyces species during a screen for herbicidal compounds [196], It was fotind to inhibit de novo starch synthesis and it was suggested that this is due to direct inhibition of protein synthesis. Duazomycin A is structurally related to 6-diazo-5-oxo-L-norleucine (138), also reported as a natural product from Streptomyces [197], which acts as a glutamine antagonist and inhibits purine biosynthesis [198],... 

The first examples of macrocyclization by enyne RCM were used in Shair s impressive biomimetic total synthesis of the cytotoxic marine natural product longithorone A (429) [180]. This unique compound features an unusual hep-tacyclic structure which, in addition to the stereogenic centers in rings A-E, is also chiral by atropisomerism arising from hindered rotation of quinone ring G through macrocycle F (Scheme 85). It was assumed that biosynthesis of 429 could occur via an intermolecular Diels-Alder reaction between [12]paracy-... 

Ichihara A., Oikawa H. Diels-Alder Type Natural Products - Structures aud Biosynthesis Curr. Org. Chem. 1998 2 365 394... 

Stipanovic R. D. Natural Product Biosynthesis Via the Diels-Alder Reaction... 

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