Synthesis of 2-Bromo- and 2-Fluoro-3-dehydroshikimic Acids and 2-Bromo- and 2-Fluoroshikimic Acids Using Synthetic and Enzymatic Approaches

González‐Bello, Concepción; Manthey, Michael K.; Harris, J. H.; Hawkins, Alastair R.; Coggins, and J. R.; Abell, Chris

doi:10.1021/jo971858i

Cited by 21 publications

(11 citation statements)

References 26 publications

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“…This opportunity has been successfully exploited by Abell et al 62 with the haloderivatives (2R)-2-fluoro-(16) and (2R)-2-bromo-3-dehydroquinic acid (17), 63 where the replacement of the pro-R hydrogen of 3-dehydroquinic acid (4) by a halogen (fluorine or bromine) makes these compounds excellent substrates for the type II dehydroquinases; they are rapidly converted into the corresponding 2-fluoro-(18) and 2-bromo-3-dehydroshikimic acid (19), respectively (Table I). In contrast, compounds 16 and 17 are not substrates for the type I enzyme and were found to be time-dependent irreversible inhibitors of type I dehydroquinase (E. coli) with K i values of 80 mM and 3.7 mM, respectively.…”

Section: F I R S T G E N E R a T I O N I N H I B I T O R S O F T Y mentioning

confidence: 95%

Progress in type II dehydroquinase inhibitors: From concept to practice

González‐Bello

Castedo

2006

Medicinal Research Reviews

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Scientists are concerned by an ever-increasing rise in bacterial resistance to antibiotics, particularly in diseases such as malaria, toxoplasmosis, tuberculosis, and pneumonia, where the currently used therapies become progressively less efficient. It is therefore necessary to develop new, safe, and more efficient antibiotics. Recently, the existence of the shikimic acid pathway has been demonstrated in certain parasites such as the malaria parasite. These types of parasites cause more than a million casualties per year, and their effects are particularly strong in people with a compromised immune system such as HIV patients. In such cases it is possible that inhibitors of this pathway could be active against a large variety of microorganisms responsible for the more opportunistic infections in HIV patients. Interest in this pathway has resulted in the development of a wide variety of inhibitors for the enzymes involved. This review covers recent progress made in the development of inhibitors of the third enzyme of this pathway, i.e., the type II dehydroquinase. The X-ray crystal structures of several dehydroquinases (Streptomyces coelicolor, Mycobacterium tuberculosis, etc.) with an inhibitor bound in the active site have recently been solved. These complexes identified a number of key interactions involved in inhibitor binding and have shed light on several aspects of the catalytic mechanism. These crystal structures have also proven to be a useful tool for the design of potent and selective enzyme inhibitors, a feature that will also be discussed.

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Section: F I R S T G E N E R a T I O N I N H I B I T O R S O F T Y mentioning

confidence: 95%

Progress in type II dehydroquinase inhibitors: From concept to practice

González‐Bello

Castedo

2006

Medicinal Research Reviews

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“…Key reactions in this synthesis are the a-face-selective chlorination of silylenol ether, derived from known ketone 31, and the reagent-dependent stereoselective reductions of enones 39 and 40. Lactone 30, which was derived from (À)-quinic acid following the literature [87,88], was chlorinated with NCS with excellent face selectivity to give a-chloroketone 32 via silylenol ether in 45% yield in two steps. The subsequent stereoselective reduction of 32 with NaBH 4 gave alcohol 33 as the sole product.…”

Section: Syntheses Of Initially Assigned Pericosine a And Its Diastermentioning

confidence: 99%

Synthesis of Marine-Derived Carbasugar Pericosines

Usami

2014

Studies in Natural Products Chemistry

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“…other halogen-substituted shikimate-pathway intermediates were prepared either by chemical synthesis [22] or by a combination of chemical synthesis and biotransformation [23,24]. Among the first compounds made were the two stereoisomers of 6-fluoroshikimate, which were transformed into the corresponding 6-fluoroEPSPs and shown to be inhibitors of chorismate synthase [25].…”

Section: First Steps In Inhibitor Developmentmentioning

confidence: 99%