Computer Science, Biology & Chemistry have opened faculty searches

Brandeis has open searches for tenure-track faculty in three departments within the Division of Science for this fall.  We are looking forward to a busy season of intriguing seminars from candidates this winter.

1. Assistant Professor of Computational Linguistics. Computer Science invites applications for a full-time, tenure-track assistant professor, beginning Fall 2019, in the area of Computational Linguistics including, but not limited to Statistical and Neural Machine Translation, Question Answering, Information Extraction, Text Summarization, Syntactic and Semantic Parsing, Dialogue Systems, etc.
2. Assistant Professor(s) of Biology Biology invites applications for up to two full-time tenure-track positions at the level of Assistant Professor, beginning Fall 2019. Ideal candidates will be conducting innovative research in the broad area of cell biology using any organismal, cellular or in vitro system. Areas of emphasis include, but are not limited to, cell architecture, cell motility, cell division and morphogenesis, organelle function, intracellular trafficking, and compartmentalization.
3. Assistant Professor of Chemistry. Chemistry is seeking a creative individual at the assistant professor level for a tenure-track faculty position in organic chemistry or chemical biology.  Exceptional senior candidates in all areas of chemistry will also be considered at the appropriate rank.

Brandeis University is an equal opportunity employer, committed to building a culturally diverse intellectual community, and strongly encourages applications from women and minorities.  Diversity in its student body, staff and faculty is important to Brandeis’ primary mission of providing a quality education.  The search committees are therefore particularly interested in candidates who, through their creative endeavors, teaching and/or service experiences, will increase Brandeis’ reputation for academic excellence and better prepare its students for a pluralistic society.

Putting “umpolung” to work in synthesis of nitrogen-bearing stereocenters

Professor Li Deng‘s lab in the Brandeis Chemistry Department has recently published a high-profile paper in Nature, disclosing an important advance in the chemical synthesis of organic molecules containing nitrogen.

A great number of important drugs contain at least one nitrogen atom connected to a “stereogenic” carbon atom. Stereogenic carbons are connected to four different groups, making possible two different configurations called “R-” or “S-”. In synthesizing a drug, it can be disastrous if the product does not have the correct R/S configuration.  For instance, the morning-sickness drug Thalidomide caused birth defects in ~10,000 children because it was a mixture of R and S molecules.

Selective preparation of only R or only S molecules containing nitrogen is a major challenge in organic chemistry. Many recent approaches have formed such stereocenters by use of an electron rich “nucleophile” to attack an electron poor “imine”. Deng is now the first to report an unconventional strategy in which the polarity of the reaction partners is reversed. In the presence of base and a creatively designed catalyst, the imine is converted into an electron rich nucleophile, and can attack a variety of electrophiles. Deng’s catalysts are effective in minute quantities (as low as 0.01 % of the reaction mixture), and yield products with R- or S- purities of 95-98 %.

In addition to Professor Deng, authors on the paper included former graduate student Yongwei Wu PhD ’14, current Chemistry PhD student Zhe Li, and Chemistry postdoctoral associate Lin Hu.

Wu Y, Hu L, Li Z, Deng L. Catalytic asymmetric umpolung reactions of imines. Nature. 2015;523(7561):445-50. (commentary)

Noam Saper ’15 named Goldwater Scholar

Noam Saper ’15, a Brandeis Chemistry major, has been named a Goldwater Scholar by The Barry Goldwater Scholarship and Excellence in Education Program. An exceptional student, Noam has been doing research with Christine Thomas and also with Barry Snider, seeking out experience in both organic and inorganic synthetic chemistry, with publication in press already from each lab.  Noam was a 2013 recipient of a Division of Science Summer Research Fellowship and a Teaching Assistant for Organic Chemistry Lab. He is also a Lerman-Neubauer Fellow, an Undergraduate Departmental Representative for Chemistry, and an active member in the Brandeis Orthodox Organization, In short, Noam is a hard-working and engaged member of the Brandeis community, and very deserving of this distinctive honor.

Noam presenting at a recent ACS national meeting

The Scholarship Program honoring Senator Barry Goldwater was designed to foster and encourage outstanding students to pursue careers in the fields of mathematics, the natural sciences, and engineering. The Goldwater Scholarship is the premier undergraduate award of its type in these fields. Goldwater Scholars have very impressive academic qualifications that have garnered the attention of prestigious post-graduate fellowship programs. Recent Goldwater Scholars have been awarded 80 Rhodes Scholarships, 117 Marshall Awards, 112 Churchill Scholarships, and numerous other distinguished fellowships such as the National Science Foundation Graduate Fellowships.

Snider named ACS Fellow

Charles A. Breskin Professor of Organic Chemistry Barry Snider has been named a Fellow by the American Chemical Society (ACS). ACS members are selected as fellows to recognize and honor their outstanding achievements in and contributions to science, the profession, and ACS. Fellows will be inducted at the ACS National Meeting in Denver on Aug. 29. Snider’s work in recent years has focused on total synthesis of natural products, a dazzling array of which are shown on his website: Recent stories on this blog discussing new syntheses from the Snider lab include:

• Biomimetic route to maldoxin
• New route to lycopodium alkaloids
• Phantasmidine, a Nicotinic Receptor Agonist from Ecuadoran Poison Frogs

 

 

Biomimetic Route to Maldoxin

In their recent Organic Letters paper entitled the Syntheses of Chloroisosulochrin and Isosulochrin and Biomimetic Elaboration to Maldoxin, Maldoxone, Dihydromaldoxin, and Dechlorodihydromaldoxin, the Snider lab at Brandeis developed an efficient biomimetic synthesis of maldoxin (4), the biological precursor of several cytotoxic natural products recently isolated from the plant endophytic fungus Pestalotiopsis fici. Chloroisosulochrin (1) was synthesized for the first time and elaborated to maldoxin (4) by a three-step biomimetic route consisting of oxidative cyclization to give spirofuranone 2, acid catalyzed ring opening to yield dihydromaldoxin (3) and a second oxidative cyclization to form maldoxin (4).

Electrophilic chlorination of phenols usually takes place unselectively at both ortho and para positions.  For the synthesis of chloroisosulochrin, they developed an ortho selective chlorination using 2,2,6,6-tetramethylpiperidine and sulfuryl chloride.  Presumably a hindered N-chloroamine is formed, which hydrogen bonds to the phenol and delivers electrophilic chlorine intramolecularly.

An alternative to scuba diving

Many promising medicinal agents (anti-cancer, anti-bacterial, anti-viral and anti-fungal) have been discovered among the diverse molecules produced by marine organisms. However, scuba-diving to harvest sponges and algae is not usually a practical way of obtaining usable quantities of these compounds, especially if they are present only in trace quantities in the source organisms.

A recently published paper in Organic Letters from the laboratory of Assistant Professor of Chemistry Isaac Krauss is the first to present a synthetic laboratory approach to the preparation of the bromophycolides, originally isolated from Callophycus Serratus, a red algae which was collected off the coast of Fiji. Although these compounds were shown to posses anti-tumour, anti-HIV and anti-malarial properties, algae collected in a second expedition to Fiji apparently contained none of the natural product (hence the desirability of a laboratory synthesis). The bromophycolides are a structurally unique family of natural products containing brominated asymmetric carbon centers and large 19-membered rings. This paper illustrates the preparation of the bromophycolide A and D ring system in high enantiomeric purity via a short (9-step) synthetic sequence.

New route to lycopodium alkaloids

The lycopodium alkaloids are a large and extensively studied alkaloid family. Huperzine A (1), the medicinally most significant lycopodine alkaloid as a potential treatment for Alzheimer’s disease, functions as an acetylcholinesterase inhibitor but may have other roles as has been addressed in several recent reviews.  Sauroine (2, 7,8-dihydroxylycopodine), from Huperzia saururus, was reported in 2004 and shown in 2009 to improve memory retention in the step-down test in male Wistar rats, significantly increasing hippocampal plasticity. 7-Hydroxylycopodine (3), from Huperzia serrata, was also reported in 2004 and may have related biological activity.

In their recent Organic Letters paper entitled the Synthesis of (±)-7-Hydroxylycopodine, the Snider lab at Brandeis developed a new general route to these bridgehead hydroxylated lycopodines. They reported a practical six-step synthesis of 7-hydroxylycopodine which makes it readily available for further biological evaluation. The key step of the synthesis is the treatment of bicyclic enol ether 4 with 60% sulfuric acid that affords tricyclic amino alcohol 5, which is further elaborated to 7-hydroxylycopodine (3) in three steps. The application of this route to the synthesis of sauroine (2) is now under investigation.

Phantasmidine, a Nicotinic Receptor Agonist from Ecuadoran Poison Frogs

IIn 1992, the lab of the late John Daly at NIH reported the isolation of epibatidine (1) from the skin of an Ecuadorian poison frog.  In addition to being a toxin, epibatidine has potent analgesic activity. Subsequent studies showed that this activity resulted from interaction with acetylcholine nicotinic receptors (nAChRs) with binding to some of the receptors at sub nanomolar levels.  The binding to several different types of nAChRs may be responsible for its non-selective activity.

In 2010, the Daly group reported the isolation and tentative structure determination of the epibatidine congener phantasmidine (2) from a total sample of only 20 micrograms. Preliminary biological studies with the limited material available indicated that phantasmidine (2) differs from epibatidine (1) by being selective for β4-containing nicotinic receptors, suggesting that phantasmidine might fill a niche for characterization of these receptors. However, the limited natural material available precluded detailed pharmacological analysis and definitive structure determination.

In their recent paper in Organic Letters entitled the Synthesis of Phantasmidine, the Snider lab at Brandeis reported a short and efficient synthesis of phantasmidine that confirmed the tentative structure and makes ample material readily available for further biological evaluation, which is currently in progress.  To prepare the tetracyclic framework, they invented a new tandem intramolecular aldol reaction-nucleophilic aromatic substitution reaction to form both five membered rings in a single reaction.   Treatment of keto amide 3 with sodium hydroxide gave aldol adduct 4 which cyclized to lactam 5.  Reduction of the lactam completed a practical synthesis of phantasmidine (2).

Back to class

2010 Beckman Scholar Philip Braunstein ’12 discusses his research project in the Hedstrom lab at the last class meeting of Organic Chemistry CHEM 25a. Training the scholars in communicating science and improving the visibility of undergraduate research are key components of the Beckman Scholars program.

Photographs by Nathaniel Freedman