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: Researchers use neutron scattering and supercomputing to study shape of a protein involved in cancer

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

SANS: a unique technique to look inside plants' leaves

Mar 26, 2015

Plants' leaves capture the sunlight and convert it into the energy used to produce nutrients for their activities. This process is accomplished thanks to the presence of the thylakoid membrane system. While ...

Silver shines as antibacterial for medical implants

Mar 24, 2015

There have been growing concerns in the global health care system about the eradication of pathogens in hospitals and other patient-care environments. Overuse of antibiotics and antimicrobial agents has contributed ...

Fat turns from diabetes foe to potential treatment

Mar 24, 2015

A new weapon in the war against type 2 diabetes is coming in an unexpected form: fat. Researchers have discovered a new class of potentially therapeutic lipids, called fatty-acid esters of hydroxy fatty acids (FAHFAs). These ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.