Function oriented synthesis: preparation and initial biological evaluation of new A-ring-modified bryologs

Wender, Paul A.; Reuber, Jenny

doi:10.1016/j.tet.2011.09.058

Cited by 14 publications

(7 citation statements)

References 56 publications

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“…A number of simplified bryostatin analogues (often called "bryologs") have been synthesized using methods such as functionoriented synthesis. This technique was employed by Wender and other workers to develop simplified analogues with comparable or much improved activities, in some cases orders of magnitude in in vitro assays [136][137][138]. Further information was given in a review by Newman [139] and in a recent 2013 paper by the Keck group [140].…”

Section: Bryostatin 1 and "Latent" Hivmentioning

confidence: 99%

Drugs and Drug Candidates from Marine Sources: An Assessment of the Current “State of Play”

2016

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The potential of the marine environment to produce candidate compounds (structures) as leads to, or even direct drugs from, has been actively discussed for the last 50 or so years. Over this time frame, several compounds have led to drugs, usually in the area of cancer (due to funding sources). This review is designed to show where there have been successes, but also to show that in a number of disease areas, there are structures originally isolated from marine invertebrates and free-living microbes that have potential, but will need to be ?adopted? by pharmaceutical houses in order to maximize their potential.

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Section: Bryostatin 1 and "Latent" Hivmentioning

confidence: 99%

Drugs and Drug Candidates from Marine Sources: An Assessment of the Current “State of Play”

2016

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“…[6d] These studies were primarily driven by the guiding principle that the bryostatin core structure could be divided into the upper "binding" or "recognition domain" (C1-C14) and lower "spacer domain" (C15-C27) according to its interactions with PKC ( Figure 9). [86] Studies on bryologs have examined the significance of the Aring, [87] the Bring, [88] the C20 [89] and C7 side chains, [90] as well as de novo structures, [91] among others. [92] Notable examples of analogues include picolog synthesized by Wender et al (reported in 2002 with aP KC binding affinity of 0.25 nmol L À1 ), which was synthesized in 29 steps with al ongest linear sequence of 19 steps.…”

Section: Angewandte Chemiementioning

confidence: 99%

Capturing Biological Activity in Natural Product Fragments by Chemical Synthesis

2016

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Natural products have had an immense influence on science and have directly led to the introduction of many drugs. Organic chemistry, and its unique ability to tailor natural products through synthesis, provides an extraordinary approach to unlock the full potential of natural products. In this Review, an approach based on natural product derived fragments is presented that can successfully address some of the current challenges in drug discovery. These fragments often display significantly reduced molecular weights, reduced structural complexity, a reduced number of synthetic steps, while retaining or even improving key biological parameters such as potency or selectivity. Examples from various stages of the drug development process up to the clinic are presented. In addition, this process can be leveraged by recent developments such as genome mining, antibody–drug conjugates, and computational approaches. All these concepts have the potential to identify the next generation of drug candidates inspired by natural products.

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“…Synthetic approaches to generating the bottom (Nakagawa-Goto and Crimmins 2011a) and top fragment of bryostatin 11 have also been described (Nagakawa-Goto and Crimmins 2011b). The synthesis of bryostatin analouges (bryologs) has also been reported (Wender and Reuber 2011;Wach and Gademann 2012). These are simpler and therefore lend themselves more easily to synthesis .…”

Section: Bryostatins and Other Substances From Bryozoansmentioning

confidence: 85%

Biologically active substances from water invertebrates: a review

Šinko¹,

Rajchard²,

Balounová³

et al. 2012

Vet. Med. - Czech

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Some species of invertebrates especially bryozoans (Bryozoa syn. Ectoprocta) and marine sponges (Porifera) are very important sources of pharmacologically exploitable compounds. These substances are probably produced to protect themselves from fish predators and may be an advantage in competition. The real sources of compounds with these antipredatory effects are probably not marine invertebrates themselves, but microscopic symbionts or food which they feed on. Bryostatins from bryozoan species Bugula neritina are produced by a bacterial symbiont called Candidatus Endobugula sertula. They have significant anti-cancer effects, but also other therapeutic benefits. Compounds with the structure of bryostatins were also discovered in some other invertebrates. Sponges are a source of many compounds, e.g., ara-A (vidarabine), manzamine, lasonolides, spongistatins, peloruside and others with antimicrobial, anti-cancer, immunosuppressive and similar activities. Other important sources of compounds with medical effects are tunicates (Tunicata syn. Urochordata) and some snails (Mollusca). One drug was developed from tunicates – Yondelis against refractory soft-tissue sarcomas. Certain other drugs originate from snails: e.g., prialt, which acts against chronic pain in spinal cord injury.  

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Function oriented synthesis: preparation and initial biological evaluation of new A-ring-modified bryologs

Cited by 14 publications

References 56 publications

Drugs and Drug Candidates from Marine Sources: An Assessment of the Current “State of Play”

Drugs and Drug Candidates from Marine Sources: An Assessment of the Current “State of Play”

Capturing Biological Activity in Natural Product Fragments by Chemical Synthesis

Biologically active substances from water invertebrates: a review

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