Study presents approach to access biorelevant structures by 'remodeling' natural products

Oct 24, 2011

There is an increasing need for pharmacological tools for biomedical and translational research applications. The field of diversity-oriented synthesis (DOS) has been very fruitful in providing access to numerous new molecules with diverse shapes and chemical structures in order to discover candidate molecules for therapeutic use. Boston University researchers, in a paper published in the journal Nature Chemistry, present a new approach to accessing new, biorelevant structures by "remodelling" natural products. In this case, they demonstrate how the natural product derivative fumagillol can been remodelled to access a collection of new molecules using highly efficient chemical reactions.

"Overall, these studies should pave the way for work to identify pharmacological tools for use in CNS research, oncology, and as anti-infective agents," said John A. Porco, Jr., professor of chemistry at Boston University. "These studies also will enable future studies to remodel additional natural product scaffolds to access novel therapeutic agents."

In the search for novel biologically active molecules, DOS strategies break through the limitation of traditional library synthesis by sampling new chemical space. Many can be regarded as useful starting points for DOS, wherein stereochemically rich core structures may be reorganized into chemotypes that are distinctly different from the parent . Ideally, to be suited to library applications, such transformations should be general and involve few steps.

With this objective in mind, Porco and colleagues including Professor John Snyder and postdoctoral fellow Dr. Brad Balthaser successfully remodelled the highly oxygenated natural product fumagillol in several ways using a reaction-discovery-based approach. In reactions with amines, excellent selectivity in a bis-epoxide opening/cyclization sequence was obtained using the appropriate metals catalysts forming either perhydroisoindole or perhydroisoquinoline products. Perhydroisoindoles were further remodelled to other complex structures including novel benzoxazepines.

Explore further: Chemical biologists find new halogenation enzyme

More information: Nature Chemistry, 23 OCTOBER 2011 DOI: 10.1038/NCHEM.1178

Provided by Boston University Medical Center

not rated yet
add to favorites email to friend print save as pdf

Related Stories

Breaking new ground in synthesis of anti-cancer agents

Nov 18, 2010

An anti-cancer research jointly conducted by The Hong Kong Polytechnic University (PolyU) and Peking University Shenzhen Graduate School (PKUSZ) has led to the first total synthesis of an anti-cancer marine ...

Chemists discover twisted molecules that pick their targets

Aug 10, 2009

New York University chemists have discovered how to make molecules with a twist—the molecules fold in to twisted helical shapes that can accelerate selected chemical reactions. The research, reported in the latest issue ...

Recommended for you

Chemical biologists find new halogenation enzyme

11 hours ago

Molecules containing carbon-halogen bonds are produced naturally across all kingdoms of life and constitute a large family of natural products with a broad range of biological activities. The presence of halogen substituents ...

Protein secrets of Ebola virus

16 hours ago

The current Ebola virus outbreak in West Africa, which has claimed more than 2000 lives, has highlighted the need for a deeper understanding of the molecular biology of the virus that could be critical in ...

Protein courtship revealed through chemist's lens

16 hours ago

Staying clear of diseases requires that the proteins in our cells cooperate with one another. But, it has been a well-guarded secret how tens of thousands of different proteins find the correct dancing partners ...

Decoding 'sweet codes' that determine protein fates

19 hours ago

We often experience difficulties in identifying the accurate shape of dynamic and fluctuating objects. This is especially the case in the nanoscale world of biomolecules. The research group lead by Professor Koichi Kato of ...

Conjecture on the lateral growth of Type I collagen fibrils

Sep 12, 2014

Whatever the origin and condition of extraction of type I collagen fibrils, in vitro as well as in vivo, the radii of their circular circular cross sections stay distributed in a range going from 50 to 100 nm for the most ...

User comments : 0