Manipulation of natural product

Pirn RD, Jones CG. (1999). Secondary metabolism and GMOs. Nature, 400,13-14. See also Eirn RD. (2006). The genetic manipulation of Natural Product composition—risk assessment when... 

This chapter shows how radical chemistry based on thiocarbonyl derivatives of secondary alcohols can be useful in the manipulation of natural products and especially in the deoxygenation of carbohydrates. From the original conception in 1975, the variety of thiocarbonyl derivatives used has increased, but the methyl xanthate function still remains the simplest and cheapest, when other functionality in the molecule does not interfere. Otherwise, selective acylation with aryloxythiocarbonyl reagents is important. Many of the functional groups present in carbohydrates and other natural products do not interfere with radical reactions. 

Many of the same reagents that reduce vic-dihalides also reduce halohydrins with similar regiochemi-cal and stereochemical advantages. However, halohydrins are more useful alkene precursors because they can be prepared by a greater variety of methods. The Fischer-Zach synthesis of 3,4,6-tri-O-acetyl-D-glucal (11 Scheme 3) reported in 1913 is one of the first synthetically useful applications of reductive elimination reactions to the manipulation of natural products and the method is still widely used today. ... 

The use of these cyclobutano sugars has been developed for the synthesis of natural products such as grandisol [47]. Both enantiomers of this pheromone are available by 2 + 2 photoaddition of ethylene to methyl hex-2-enopyranosid-4 ulose 44. After further manipulations, ( + ) and (—) grandisol (45, 46) are synthesized following Scheme 21. 

However, the majority of natural products were not created to meet human needs and domestication in the form of chemical manipulation is required to increase potency, improve selectivity and reach a clinically acceptable pharmacokinetic and safety profile. Thus, while antibiotics are generated by microorganisms to fight other microorganisms and can be employed clinically to do so, natural cytotoxic agents are not produced to kill cancer cells and they... 

Synthetic Applications. (5 )-Dihydro-5-(hydroxymethyl)-2(3H)-furanone (2) was first described in 1971 as an intermediate in the synthesis of o-ribose from r-glutamic acid. Since then, this lactone and its (f )-enantiomer have found widespread use as chirons for constructing a rich variety of natural products ranging from simple pheromones to complex macrocycles and ionophore antibiotics. The chemical manipulation of these chirons often involves lactone cleavage at an early stage, - - as illustrated by the preparation of suitable intermediates for the synthesis of the Vespa orientalis pheromone (R)-S-n-hexadecanolactone (14) (eq 4), the antiviral fungal metabolite brefeldin A (15) (eq 5), and (7aa)-cp/-hemibrevetoxin B (16) (eq 6). ... 

In summary, the marine environment contains a wealth of plants, animals and microorganisms. Due to their unique adaptations to their ocean habitat, they contain a wide diversity of natural products. These compounds have shown activity in a variety of assays which have relevance to human diseases. As our understanding of the molecular basis of disease expands, these compounds and ones yet to be discovered will provide lead compounds for human therapeutic treatment. Innovations in synthesis, fermentation of symbionts as well as in manipulation of biosynthetic genes will allow us to produce sufficient material for clinical use of the compounds. Marine organisms provide a unique opportunity for access to chemical diversity. 

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