Current Natural Product Targets

 

Anthracimycin: With the dire need for new antibiotics being constantly highlighted by both government and health professionals we have initiated studies directed at completing the first total synthesis of anthracimycin. This recently isolated marine natural product has potent antibacterial activity and an unknown mode of action. We aim to produce quantities of the natural product and strutural analogues in order to probe anthracimycin's mode of action and determine whether it has the potential to be a new weapon in the war against antibiotic resistance "superbugs".

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Streptosetin A: Is a recently isolated marine-derived actinomycetes which exhibits human class III HDAC (SIRT) inhibition. This is interesting as other inhibitors demonstrate apoptotic and autophagic cell death in breast cancer cell lines. We are progressing a total synthesis of this molecule due to its biological activity and its interesting decalin and tetramic acid structural features.

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Completed Natural Product Targets

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(±)-Centrolobine: Use of a 3 component, one pot reaction for the formation of highly substituted tetrahydropyrans has enabled us to synthesise the antibiotic molecule centrolobine in only 4 steps.

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(±)-Civet Cat Secretion: Use of the dihydropyran version of the Maitland-Japp reaction has enabled the diastereoselective synthesis of the molecule found in Civet cat secretion.

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(±)-Citreothiopyrane A: Use of a thiopyranone modification of the Maitland-Japp reaction has led to the synthesis of this metabolite of penicillium citreo-viride B. IFO 6200 and 4692, a natural product with plant growth inhibition activity.

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(±)-Diospongin A and B: Application of our stereodivergent oxy-Michael reaction has furnished efficent syntheses of both natural products from a single precursor. These natural products have anti-osteoperotic activity comparable with current treatments.

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(-)-Irnidine and (-)-bgugaine: Are natural products with DNA binding affinity and antimicrobial properties against Gram+ve bacterial. Asymmetric 'Clip-Cycle' reactions generated their pyrrolidine core which were converted into these natural products in only 4 steps.

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Natural Products Partial and Formal Syntheses

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(+)-Phorboxazole B: Is a potent anticancer agent which is no longer available from nature. Our highly convergent approach has resulted in the synthesis of the macrocyclic core and uses our recent development of the asymmetric Maitland-Japp pyran forming reaction to generate the C1-C19 bis-pyran unit and a novel stereodivergent Michael reaction to rapidly assemble the C20-C32 unit. 

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Austrodoranes and Pinguisanes: Novel transannulation strategies have been used to constructhighly funcationalised ring systems present in the austrodorane and pinguisane classes of sesquiterpene natural products. 

 

 

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Hexacyclinic Acid: Is a hexacyclic molecule with modest anti-cancer activity and a unique fused-bridged ring system. The group has developed strategies for the synthesis of all of the key ring sytems, using a Diels-Alder reaction to form the ABC rings and an unprecedented transannulation reaction of a ketone carbonyl onto a double bond to form the DEF rings.

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