Scavengers natural product synthesis

Application of Polystyrene Resin-Supported Scavengers in a Flow-through Platform towards Combinatorial Libraries and Natural Product Synthesis... 

Netherton and Fu [46] recommended the conversion of air-sensitive triphe-nylphosphines to their phosphonium salts (e.g., by the addition of HBF4) the phosphine is liberated in situ by a Bronsted base under the reaction conditions. Liebeskind et al. [47] introduced Ph2P02NBu4 as the so-called tin scavenger it has since been employed by other groups [48, 49] for intramolecular vinyl/vinyl coupling in natural product synthesis (see later discussion). 

Baxendale IR, Lee A-L, Ley SV (2001) A concise synthesis of the natural product carpanone using solid-supported reagents and scavengers. Synlett 482-484... 

Ley S V, Baxendale IR, Myers RM (2006) The use of polymer supported reagents and scavengers in the synthesis of natural products. In Boldi AM (ed) Combinatorial synthesis of natural product-based libraries. CRC Press Boca-Raton, pp 131-163... 

Scheme 74 Continuous flow protocol employed for the synthesis of the natural product grossamide (260) using a series of solid-supported reagents, catalysts and scavengers.

Snider et al. have synthesised the antiinsectan ( )-leporin [496] 7-26 using the domino-Knoevenagel-hetero Diels-Alder sequence. The intermediate 1-oxa-1,3-butadiene 7-25 was formed in situ by condensation of the pyridone 7-23 and the dienal 7-24. Subsequently, a hetero Diels-Alder reaction occurred accompanied by minor side reactions. Thus, the desired cycloadduct 7-27 was formed only in moderate yield as 5 1 mixture with its trans-fused diastereomer (Fig. 7-6). Functionalisation of the nitrogen atom yielded the natural product. A similar reaction sequence occurred in the synthesis of the structurally related free radical scavenger ( )-pyridoxatin, however, in this approach the hetero Diels-Alder reaction represented only a side reaction competing with the desired intramolecular ene reaction [497]. 

Amine scavengers have been one of the most developed and widely used to remove a range of electrophiles on several different platforms. Traditionally developed on a polystyrene bead, amine scavengers have been utilized in natural products or library synthesis to yield high purity via a facilitated protocol. In 2005, Liu reported the use of a polystyrene-bound amine scavenger for the removal of excess aldehydes to provide imidazole derivatives in high purity without the need for classical purification (Scheme 8.30) [42]. 

As previously described in the residual removal of palladium, the residual presence of other metals from catalysis has also been an area of concern. The emergence of the ruthenium-based Grubbs catalyst has led to its application in the synthesis of complex natural products and libraries. The removal of residual catalyst from the product, however, has remained a problem. One approach to circumvent this problem was reported by Breinbauer, who scavenged residual ruthenium using an inexpensive polymer-bound chelate phosphine [47]. Scavenging of crude mixtures removed ruthenium to give the desired product in >95% purity (Scheme 8.34). 

In 2006, Ley reported the application of a continuous flow-through platform for the preparation of the neolignan natural product Grossamide (Scheme 8.48) [63], This was the first report of the enantioselective total synthesis of Grossamide utilizing a fully automated and scalable flow reactor with supported-reagents and scavengers. This principle has a wider impact on multiple step assembly of libraries and natural products. 

Further examples have been reported by Ley in recent years, utilizing both designer cartridges of reagents and scavengers for both the synthesis of small libraries and natural products [2a, 64]. 

Anti-inflammatory compounds can act at different levels. They can, for example, decrease vasodilatation and edema, as in the case of antihistaminic drugs inhibit PGs synthesis as do the non-steroidal antiinflammatory drugs modify synthesis or block the receptors of mediators such as PAF or LTs interfere with the functions of peptide mediators block the transcription factors or scavenge free radicals generated in the process. Natural products as anti-inflammatory agents may act at different levels, some by non specific pathways as antioxidants do or by a specific mechanism via receptor antagonism. The lignans can act in both cases. 

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