from NERM Memoirs€¦ · 2 The Nucleus December 2013 The Board of Directors of the North - east Region of the ACS, Inc. (NER - ACS) met on Saturday, October 26, 2013, in the Omni

http://www.nesacs.org

December 2013 Vol. XCII, No. 4

NORTHEASTERN SECTION • AMERICAN CHEMIC

ALSO

CIET

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FOUNDED 1898

NESACS

Monthly MeetingA Medicinal Chemistry Symposium atGenzyme/Sanofi in Waltham

Photos and Reportsfrom NERMBy Morton Z. Hoffman

Summer Scholar ReportAsymmetric Mannich Reactions via PseudoephenamineGlycinamide Enolization. By Claire S. Harmange, Ian B.Seiple, Robin J. Sussman, Andrew G. Myers

NAS BiographicalMemoirsBy Michael Filosa

2 The Nucleus December 2013

The Board of Directors of the North-east Region of the ACS, Inc. (NER-ACS) met on Saturday, October 26,2013, in the Omni New Haven Hotelon the occasion of the NortheastRegional Meeting (NERM 2013). TheNERACS Board consists of its Chair(Julianne Smist, Springfield College),Vice Chair (Richard Cobb, EastmanKodak, retired), Secretary (ChristopherMasi, Westfield State University),Treasurer (Wayne Jones, SUNY Bing-hamton), and representatives from thefollowing local sections: Binghamton,Central Massachusetts, Central NewYork, Connecticut Valley, Cornell,Corning, Eastern New York, GreenMountain, Maine, Mid-Hudson, NewHaven, Northeastern, Northern NewYork, Penn-York, Rhode Island,Rochester, Western Connecticut, West-ern New York.

In addition to executive officersSmist, Cobb, and Masi, the followinglocal section representatives were pres-ent at the meeting: Willem Leenstra(Green Mountai n), Mark Zell (RhodeIsland), Akiko Fillinger (Cornell),Richard Hartmann (Rochester),Mitchell Bruce (Maine), KennethWhite and Jefferson Chin (NewHaven), Morton Hoffman (Northeast-ern). Also in attendance were ThomasGilbert (ACS District I Director) andMichelle Stevenson (ACS staff liaisonto NERM).

The Board elected Richard Cobband Willem Leenstra as Chair and ViceChair, respectively, for two-year terms(2014-15). It voted by acclamation itsappreciation for the service JulianneSmist provided as Chair for six yearsfrom the time of the incorporation ofNERACS. The terms for the currentSecretary and Treasurer run through2014.

It was announced that the assets inthe NERACS Treasury are close to$50,000; when they reach that level,discussions will take place concerningthe long-term use of those funds. At

the present time, any income aboveexpenditure for a NERM is shared in a40/60 ratio between NERACS and thehosting local section.

Cobb expressed concern about thepaucity of nominations for the regionawards that are presented at NERM; infact, some awards cannot be givenbecause the number of nominationsdoes not reach the stipulated minimum.He asked the representatives of thelocal sections to urge their officers andmembers to be active in the nomina-tion process. Inasmuch as there will beno NERM in 2014, there is now ampletime for nominations to be generatedfor the 2015 cycle of the followingNortheast Region awards: Achieve-ments in the Chemical Sciences,Excellence in High School Teaching,Volunteer Service to the ACS, Advanc-ing Diversity in the Chemical Sci-ences.

It was reported that as of thatmorning, more than 850 registrationshad been received for NERM 2013;over 480 oral and poster presentationswere included in the program. Therewere 140 undergraduate researchposters, four high school studentposters, and 27 exhibitors at the meet-ing. Although the room quota had notbeen met at the Omni Hotel, whichwill result in some penalty, overall the

financial balance sheet for the meetingshould be in positive territory.

NERM 2015 will be held at IthacaCollege, June 10-13, with Akiko Fill-

Report from New Haven: Meeting of theBoard of Directors of NERACSMorton Z. Hoffman, NESACS Representative to the NERACS Board [[email protected]]

Sharon Palmer (Amherst Regional HighSchool), flanked by Marinda Wu (ACS Presi-dent) at left and Julie Smist (NERACS Chair),receiving the 2013 Division of Chemical Educa-tion Northeast Region Award for Excellence inHigh School Teaching.

(Photos by M. Z. Hoffman)

Doris Lewis (Suffolk University), flanked byMarinda Wu (ACS President) at left and JulieSmist (NERACS Chair), receiving the 2013 E.Ann Nalley Northeast Region Award for Volun-teer Service to the ACS.

continued on page 12

The Nucleus December 2013 3

The Nucleus is published monthly, except June and August, by the Northeastern Section of the AmericanChemical Society, Inc. Forms close for advertising on the 1st of the month of the preceding issue. Textmust be received by the editor six weeks before the date of issue.Editor: Michael P. Filosa, Ph.D., 18 Tamarack Road, Medfield, MA 02052 Email:

filosam(at)verizon.net; Tel: 508-843-9070Associate Editors: Myron S. Simon, 60 Seminary Ave. apt 272, Auburndale, MA 02466,

Mindy Levine, 516-697-9688, mindy.levine(at)gmail.comBoard of Publications: Mary Mahaney (Chair), Vivian K. Walworth, James PhillipsBusiness Manager: Karen Piper, 19 Mill Rd., Harvard, MA 01451, Tel: 978-456-8622Advertising Manager: Vincent J. Gale, P.O. Box 1150, Marshfield, MA 02050,

Email: Manager-vincegale(at)mboservices.net; Tel: 781-837-0424Contributing Editors: Morton Hoffman, Feature Editor; Dennis Sardella, Book Reviews Calendar Coordinator: Michael P. Filosa, email: Michael.filosa(at)verizon.netPhotographers: Morton Hoffman and James PhillipsProofreaders: Donald O. Rickter, Vivian K. Walworth, Mindy Levine Webmaster: Roy HagenCopyright 2013, Northeastern Section of the American Chemical Society, Inc.

The Northeastern Section of the AmericanChemical Society, Inc.Office: Anna Singer, 12 Corcoran Road,Burlington, MA 01803(Voice or FAX) 781-272-1966.e-mail: secretary(at)nesacs.orgNESACS Homepage:http://www.NESACS.orgOfficers 2013ChairLiming Shao158South Great RoadLincoln, MA 01773limingshao(at)comcast.netshao(at)fas.harvard.edu781-518-0720Chair-ElectCatherine CostelloBoston University School of Medicine670 Albany Street, room 511Boston, MA 02118-2646cecmsms(at)bu.eduImmediate Past ChairRuth TannerOlney Hall 415BLowell, MA 01854University of Mass LowellRuth_Tanner(at)uml.edu978-934-3662Secretary:Michael SingerSigma-Aldrich3 Strathmore Rd, Natick, MA 01360774-290-1391, michael.singer(at)sial.comTreasurer:James Piper19 Mill Rd, Harvard, MA 01451978-456-3155, piper28(at)attglobal.netAuditor:Anthony RosnerArchivistTim FrigoTrustees:Peter C. Meltzer, Esther A. H. Hopkins,Michael E. StremDirectors-at-LargeDavid Harris, Stephen Lantos, James Phillips,Ralph Scannell, Mary Burgess, John BurkeCouncilors Alternate CouncilorsTerm Ends 12/31/2013Alfred Viola Mark FroimowitzMichael Singer Sophia R. SuRobert Lichter Kenneth C. MattesMary Shultz Tim FrigoLeland L. Johnson, Jr. Mukund ChorghadeTerm Ends 12/31/2014Katherine Lee C. Jaworek-LopesMichael P. Filosa Lawrence ScottDoris Lewis Andrew ScholteMorton Z. Hoffman Raj RajurPatrick Gordon John PodobinskiMary Burgess Stuart LevyTerm Ends 12/31/2015Catherine E. Costello Marietta SchwartzRuth Tanner JerryJasinskiDorothy J. Phillips Stephen LantosMichaeline Chen Norton P. PeetJackie O’Neil Wilton Virgo

ContentsReport from New Haven: NERACS _________________________2Meeting of the Board of Directors

NESACS SE-MA Area Event_______________________________4By Morton Z. Hoffman

Monthly Meeting _______________________________________5A Medicinal Chemistry Symposium “Innovative Treatments for Unmet Medical Needs” at Genzyme/Sanofi in Waltham, MA

Report from New Haven: NERM ___________________________6by Morton Z. Hoffman

NAS Biographical Memoirs_______________________________7By Michael P. Filosa

Summer Scholar Report _________________________________8Asymmetric Mannich Reactions via Pseudoephenamine Glycinamide EnolizationBy Claire S. Harmange, Ian B. Seiple, Robin J. Sussman, Andrew G. Myers

Photos from NERM____________________________________10

Cover: Pictured at the first SE-MA NESACS area event held at UMass - Dart-mouth on October 3, 2013 from L-R are Morton Hoffman, Robert Lichter, JackDriscoll, Madeleine Jacobs, Ruth Tanner and Liming Shao. (Photo courtesy ofM. Z. Hoffman)

Editorial Deadlines: February 2014 Issue: December 15, 2013March 2014 Issue: January 15, 2014

All Chairs of standingCommittees, the editor of THE NUCLEUS, and the Trustees of SectionFunds are members of theBoard of Directors. AnyCoun cilor of the American Chemical Soci-ety residing within the section area is an exofficio member of the Board of Directors.


NESACS SE-MA AreaEvent at UMass Dartmouth –October 3, 2013By Morton Z. Hoffman

Approximately 80 people came to theUniversity of Massachusetts Dart-mouth (UMD) on Thursday, October 3,to hear Madeleine Jacobs, ACS Execu-tive Director and CEO, speak on

“Everything You Always Wanted toKnow about ACS, But Were Afraid toAsk” at the first Southeastern Massa-chusetts (SE-MA) area event organizedby the Subsection Task Force (STF).Among those attending were formerand current NESACS members fromindustry and academia, nonmemberchemists and teachers from the area,representatives from the Rhode IslandLocal Section, and guests. The meet-ing also attracted a significant numberof UMD faculty and students.

The purpose of the meeting was tobegin the process of exploring the fea-sibility of establishing subsectionswithin NESACS to help connect and

engage members in areas that areremote from our Boston/Cambridgeand environs core in which almost allthe Section’s activities take place,specifically, SE-MA (Barnstable, Bris-tol, Dukes, Nantucket, and PlymouthCounties) and New Hampshire (NH).At the present time, STF has the fol-lowing membership: Morton Hoffman(Boston University), Ruth Tanner(University of Massachusetts Lowell),Robert Lichter (Merrimack Consult-ants), Jack Driscoll and JenniferMaclachlan (PID Analyzers), RobertHoward (Weeset Advisors), JerryJasinski (Keene State College) andGary Weisman (University of NewHampshire).

The meeting began with a recep-tion with light refreshments that wassponsored by the UMD Department ofChemistry and Biochemistry, which ischaired by Emmanuel Ojadi; he andLiming Shao, NESACS Chair, gavewelcoming remarks, and ProvostMohammad Karim brought greetingsfrom the administration of the Univer-sity. Jack Driscoll then spoke aboutthe purpose of the event, described themany activities that NESACS hassponsored and cosponsored in SE-MAover the past several years, and pro-vided a blueprint for the future.

Robert Lichter introduced Ms.Jacobs, who spoke about the vision(“Improving people’s lives through the

2013 NESACS Golf SponsorsLSNE Lyophilization Services of NE Strem Chemical Litman Gerson Sage Chemical DavosPrime OrganicsBrian O-Reilly, LLP, Patent LitigationJohnson MattheyIRIX PharmaceuticalsCambridge Major O’Conner Carnathan and Mack, LLCEdelstein and Co.Chengda - Social Hour Sponsor


Emmanuel Ojadi with MadeleineJacobsMadeleineJacobs meets with UMD Students


AbstractTitle: A Winding Journey of MedicinalChemistry toward the Discovery of aPotent, Selective, and Orally Bioavail-able Histamine H3 Receptor Antago-nist for Cognitive Impairment: From aBiological Concept to a DevelopmentCandidateCognitive impairment or deficit is aninclusive term to describe any charac-teristic that acts as a barrier to the cog-nition process. More than 16 millionpeople in the United States are livingwith cognitive impairment. Currently,no cognitive impairment drugs or othertreatments are specifically approved bythe Food and Drug Administration(FDA), although physicians sometimesprescribe cholinesterase inhibitors.These, however, aren’t recommendedfor routine treatment because theydon’t appear to provide lasting benefit.H3 receptor (H3R), a pre-synapticGαI/O protein-coupled auto-receptor,is widely expressed in the mammalianbrain, particularly in areas involved incognitive processes and arousal, suchas the cerebral cortex, hippocampus,basal ganglia, and hypothalamus.Blockade of H3R with selective antag-onists/ inverse agonists is hypothesizedto increase the synthesis and release ofhistamine and other neurotransmittersinvolved in alert and cognitive func-tions. We are interested in discovery

Monthly MeetingThe 936th Meeting of the Northeastern Section of the AmericanChemical SocietyOrganized by the Medicinal Chemistry Group of theNortheastern Section of the American Chemical Society

Sponsored by SanofiSymposium

Innovative Treatments for Unmet Medical NeedsDecember 12, 2013

Genzyme Corporation/Sanofi153 Second Avenue, Waltham Massachusetts 02451

Northeastern Conference Room3:00 pm Refreshments3:15 pm Welcome

Raj (SB) Rajur, Program Chair, CreaGen Biosciences, Inc.,Woburn, MA

3:20 pm Introductory RemarksNorton P. Peet, Director of Chemistry, Microbiotix, Worcester, MA

3:30 pm Barry Toure, Novartis Institute for Biomedical Research, Boston 4:15 pm John Williams, Senior Scientist, Microbiotix, Inc., Worcester, MA

“Novel Inhibitors of the Pseudomonas Type Three Secretion System”5:00 pm TBA6:00 pm Social Hour6:45 pm Dinner7:45 pm Keynote Presentation

Introduction: David Aldous, Head of Boston LGCR, Sanofi,Waltham, MASpeaker: Zhongli Gao, Genzyme-Sanofi, Waltham, MAA Winding Journey of Medicinal Chemistry toward the Discovery of a Potent, Selective, and Orally Bio-available Histamine H3Receptor Antagonist for Cognitive Impairment: From a BiologicalConcept to a Development Candidate

YOU MUST REGISTER IN ADVANCE, BUT THERE IS NO REGIS-TRATION FEE TO ATTEND THE SYMPOSIUM; DINNER RESERVATIONS ARE REQUIRED.

THE PUBLIC IS INVITEDDinner reservations should be made no later than noon, Thursday, December5th, 2013. Reservations are to be made using PayPal: http://acssymposium.com/paypal.html. Select pay with credit or debit card optionand follow the additional instructions on the page. Members, $30; Non-mem-bers, $35; Retirees, $20; Students, $10. Reservations for new members and foradditional information, contact the secretary, Anna Singer, at (781) 272-1966between 9am and 6pm or e-mail at [email protected]. Reservations notcancelled at least 24 hours in advance must be paid.


Directions to Genzyme-SanofiFrom North or South 95/Rt 128South. Take Exit 27B/Winter Street. Followthe signs for Second Avenue (stay inright lane). Take a right after theEmbassy Suites Hotel onto SecondAvenue. Go past Costco on the rightAt ADP take a right between ADPgarage and ADP offices. (There is asign directing you to Genzyme). Pro-ceed about 100 feet. Genzyme will beon the right.Link to directions: http://www.genzyme.com/~/media/Files/GenzymeCorp/PDF/directions_waltham.pdf u

http://www.genzyme.com/~/media/Files/GenzymeCorp/PDF/directions_waltham.pdf


The New Haven Local Section hostedthe ACS Northeast Regional Meeting(NERM 2013) on October 23-26 at theOmni New Haven Hotel. With morethan 850 registrants making over 480oral and poster presentations (includ-ing 140 undergraduate research posters,and four high-school student posters)as well as 27 exhibitors, the meetingwas an exciting professional eventwith ACS President Marinda Wu andImmediate Past President BassamShakhashiri in attendance. Forty-threeseparate sessions, spanning a broadspectrum of the chemical sciences,were packed into three days of pro-gramming. The full program is avail-able online at <http://nerm2013.sites.acs.org/>.

One of the sessions was theNESACS-sponsored symposium,“International Chemistry Connections,”which was organized by Heidi Tengand Morton Hoffman in celebration ofthe 13th annual exchange between theNESACS Younger Chemists Commit-tee (NSYCC) and the Jungchemikerfo-rum (JCF) of the German ChemicalSociety (GDCh). Twelve graduate stu-dents and two accompanying personsfrom Germany traveled to New Havenfor NERM after spending the previousfour days in Boston as guests ofNESACS, partaking in academic andindustrial site visits as well as culturaland social events.

The following were members ofthe German delegation: Prof. Dr.Alfred Flint (University of Rostock),Dr. Elisabeth Kapatsina (GDCh), AnnaHofmann (University of Würzburg),Torsten John (University of Leipzig),Susanne Leubner (Technical Univer-sity Dresden), Martin Lichtenthaler(University of Freiburg), Mike Neu-mann (University of Potsdam), WilmaNeumann (University of Leipzig),Tanja Scholz (RWTH Aachen Univer-sity), Denise Schütz (University ofFrankfurt), Andreas Seitz (Universityof Regensburg), Peter Sponholz (Uni-versity of Rostock), Christian Wein-berger (University of Paderborn),

Stefan Zajonc (Karlsruhe University ofEducation).

The members of the NESACSGerman Exchange Steering Committeewho attended NERM were MortonHoffman (Boston University), JackieO’Neil (Alkermes, Inc.), MichaelStrem (Strem Chemicals), Ruth Tanner(University of Massachusetts Lowell),and Heidi Teng (Sigma-Aldrich FineChemicals). Jens Breffke (Pennsylva-nia State University), who was a mem-ber of the German Exchange to Bostonfor the ACS National Meeting inAugust 2007, provided important lin-guistic and cultural insights.

The schedule of the symposium,which was held on October 25, was asfollows:1:30-1:40 p.m. Opening Remarks –

Morton Hoffman1:40-2:00 p.m. Partners for Progress

and Prosperity –Marinda Wu

2:00-2:20 p.m. Chemistry in Ger-many: Educational andResearch Opportuni-ties – Elisabeth Kap-atsina

2:20-2:40 p.m. Northeastern SectionYounger ChemistsCommittee: Connect-ing Chemists Domesti-cally and Abroad –Heidi Teng

2:40-3:00 p.m. JCF: The Connectionbetween School Edu-cation, Academia, andIndustry – Anna Hof-mann

3:00-3:10 p.m. Intermission3:10-3:30 p.m. Problem with Teaching

Chemistry at HighSchools in Germany –Alfred Flint

3:30-3:50 p.m. Growing a SmallChemical BusinessInternationally –Michael Strem

3:50-4:10 p.m. Personal Impact andHow to Measure It –Jens Breffke

4:10-4:30 p.m. International Chem-istry Reflections –Morton Hoffman

4:30-4:35 p.m. Concluding Remarks –Morton Hoffman andHeidi Teng

The graduate student members of theGerman delegation also made presen-tations in the technical sessions:• Specific immobilization of biomole-

cules on surfaces for intelligent mate-rials (physical chemistry) – TorstenJohn

• Highly structured and high surface b-SiC from plant material (inorganicchemistry) – Mike Neumann

• Ordered mesoporous carbon materi-als from novel molten precursorscontaining nitrogen (nanoscience);Formation mechanism of orderedmesoporous Al2O3: Relation betweenmesoscopic order and crystallinity(poster) – Christian Weinberger

Report from New Haven: NERM 2013Morton Z. Hoffman, Chair, NERM Committee [[email protected]]


Classic New England

Michelle Stevenson (ACS), staff liaison toNERM, with Jefferson Chin (Bristol-MyersSquibb), General Co-Chair of NERM.

While searching for a photo of JamesFlack Norris (1871-1940) for theNovember Nucleus, I came across hisbiographical memoir on the website ofthe National Academy of Sciences(NAS). This memoir was written byJohn D. Roberts and was presented tothe Academy in 1974, a scant(!) 34years after his death.

The NAS was founded in 1863 by50 of the most prominent scientists inthe United States, and its initial charterwas signed by Abraham Lincoln. It is atradition that each of its members bememorialized in a memoir to the Acad-emy written by a peer (or two).

These memoirs are a treasuretrove of the history of science. Thesole weakness is that they are posthu-mous and not necessarily, very timely.However, they are quite thorough anda good overview of the scientists, com-plete with a detailed listing of theirmajor works.

During my school years, I wasalways intrigued with stories aboutgreat scientists. Dan Kemp would talkextensively about his thesis advisor, R.B. Woodward, and his works. Thosestories about Woodward (1917-1979)and also Gilbert Stork were very influ-ential in my decision to pursue syn-thetic organic chemistry as a career.

Woodward’s memoir was writtenby Elkan Blout (with assistance fromFrank Westheimer) and was publishedin 2001, a “scant” 22 years after hisdeath.

The memoirs are often glowing:“Robert Burns Woodward was the pre-eminent organic chemist of the twenti-eth century. This opinion is shared byhis colleagues, students and by otherdistinguished chemists.”

Blout includes lengthy commen-taries from Sir Derek Barton, RoaldHoffman and Albert Eschenmoser inthe memoir. He concludes with hisown insights and observations from

their long friendship. Woodward and James Conant

were influenced at Harvard by E. P.Kohler (1865-1938). Kohler’s memoirwas written by James Conant in 1952.Conant in turn was memorialized byhis student Paul D. Bartlett. Bartlettwas an immensely influential physicalorganic chemist. His memoir was writ-ten by Frank Westheimer and begins:“Paul Bartlett was one of the greatchemists of the twentieth century. Hisresearch and teaching were in the areaof physical-organic chemistry, and hedominated that field for perhaps fourdecades. He wasn’t old enough to beamong the earliest practitioners; thathonor is shared among Arthur Lap-worth, A. Hantzsch, C. K. Ingold, andL. P. Hammett. But Bartlett created aschool of physical-organic chemistrythat sparked a revolution in the wayorganic chemistry is taught and prac-ticed throughout the world.”

If the history of Harvard’s greatchemists and the development of Har-vard chemistry are not your interest,you can read the memoirs of A. C.Cope, John Sheehan or George Buchiof M.I.T. Sheehan’s memoir was writ-ten by E. J. Corey and John D.Roberts. You can also read the memoirof William Barton Rogers, founder ofM.I.T., or the memoir of VannevarBush, written by Jerome Wiesner.

Edwin Land’s memoir was writtenby his biographer, Victor K. McElheny.The memoir is a far more succinctsummary of Land’s life than the book.

The best way to find a memoir isto use the search engine. I becameintrigued with who was the first femalemember of the NAS. The searchengine did not provide a way to findthis person, but Google gave me aquick answer, Florence Rena Sabin(1871-1953), inducted into the Acad-emy in 1925. Her memoir is a fascinat-ing one and well worth reading.

Another is the memoir for MargaretMead.

Florence Rena Sabin was born inCentral City, Colorado. Her fatherabandoned the idea of a medical careerto become a mining engineer, leavingthe family farm in Vermont for Col-orado in 1860, where he married aschool teacher from Blackhawk, Col-orado in 1868. Florence’s mother diedwhen she was young and she and hersister were sent back east to live withtheir uncle and grandparents in Illinoisand Vermont. Florence ultimatelyattended Smith College with her sister.There she developed her interest in sci-ence.

Florence initially taught school inDenver and then was an assistant inzoology at Smith before working at theMarine Biological Laboratories inWoods Hole. However, her ultimateambition, once she had saved somemoney, was to attend Johns HopkinsMedical School, which was founded in1893 with the stipulation by its bene-factors that women should be admittedas well as men.

Florence became a protégé of Dr.Franklin Paine Mall, the school’s firstProfessor of Anatomy. She flourishedunder the guidance of Dr. Mall and hisphilosophy of education. Her inde-pendent work won much acclaim andshe was appointed in 1917 Professor ofHistology, the first woman to obtain afull professorship in the Johns HopkinsMedical School.

Other non-chemistry memoirs ofnote is the glowing memoir writtenabout Louis Agassiz, one of the 50founding members of the NAS. I wasalso fascinated to find the memoirs forthe two protagonists of the “DinosaurWars:” Edward Drinker Cope and Oth-niel Charles Marsh. Their biographersdo not shy away from their viciouscompetition.


National Academy of Sciences -Biographical Memoirshttp://www.nasonline.org/publications/biographical-memoirs/online-collection.html By Michael P. Filosa



Since the discovery of penicillin G (1, Fig. 1) nearly 75years ago, β-lactams are some of the most widely prescribedantibiotics in the United States and around the world. Rap-idly increasing resistance to β-lactams is threatening thelimited arsenal of antibiotics available to physicians, and thelack of innovation and momentum in the field of antibioticdevelopment has caused the drug pipeline to virtually dryout. Significant research in the practical and variable synthe-sis of antibiotics playing a central role in the battle againstresistant bacteria.1a,b

The β-lactam’s characteristic four-membered ringexerts its antibacterial effect by interfering with bacterialcell wall synthesis. In binding to the bacteria’s β-lactam-binding enzymes called PBPs (penicillin-binding proteins),the drug inhibits cell wall synthesis, eventually leading tocell death. Resistance mechanisms include: changes in oneor more of the PBPs, which decreases the drug’s ability tobind to the target bacteria; changes in cell wall porins, whichprevent penetration of the antibiotic;i and finally, bacterialproduction of β-lactamases, which deactivates the antibioticbefore it can reach its target.ii

The discovery of nocardicins (2, Fig. 1) in 1976, as wellas others, prompted new interest in the pharmaceuticalpotential of monocyclic β-lactams, which has motivatedchemists to develop a variety of routes to these compounds.iiMost notable among these is Aztreonam (3, Fig. 1), whichrepresents the only fully synthetic monobactam to be devel-oped as a commercial drug in the United States.i Develop-ments in the synthesis of monocyclic β-lactams haveincluded cyclization of amino acids,v [2+2] cycloaddition ofketenes and imines,v ester enolate-imine condensations,vi

and others.vi Asymmetric enolate-imine condensations havebeen reported using (S,S)-pseudoephedrinei and chiral oxa-zolidinones;x however, these syntheses lack amino function-ality at the C-3 position important to monocylic β-lactamsactivity. Using chemistry developed by the Myers groupwith pseudoephenamine glycinamide, this project aims tosynthesize αβ-diamino acids, which are precursors to mono-cyclic β-lactam candidates.

The Myers group has shown that stereocontrolled syn-thesis of syn-β-hydroxy-α-amino acids can be achieved viadirect aldolization of pseudoephenamine glycinamide.xi

Analoguous enolization of pseudoephenamine glycinamide(4) followed by the trapping an imine electrophile wasexpected to deliver a diastereoselective Mannich reactionand produce the desired diamine (5) β-lactam precursor(Fig. 2).

Initial challenges in the project involved the choice ofelectrophile. Trimethylsilyl-benzaldimine was at firstselected for its lability and consequent potential for simulta-neous cyclization the β-lactam and cleavage of the auxiliaryupon formation of the Mannich adduct. Several attempts toeffect a Mannich coupling with TMS-imine were unsuccess-ful, leading instead to the transimination product (6, Scheme1). By switching to Boc-imines, successful Mannich cou-pling was achieved. Boc-p-toluelbenzaldimine yielded a95% yield of major diastereomer showing promise for ahighly diastereoselective reaction (6, Scheme 2). Absolutedetermination of the product’s stereochemistry remains to bedetermined via X-ray crystollography. The success of theBoc-imine electrophile indicates potential for the synthesis

Summer Scholar ReportAsymmetric Mannich Reactions via Pseudoephenamine Glycinamide EnolizationClaire S. Harmange*, Ian B. Seiple, Robin J. Sussman, Andrew G. Myers Department of Chemistry and Chemical Biology, Harvard University

of a variety of other Mannich adducts from a variety of Boc-imines. To date, Boc-p-bromobenzaldiminexii has also beensuccessfully used as a Mannich substrate (8, Scheme 2).

Completing the β-lactam synthesis required removal of

the auxiliary and deprotection of the Boc group to yield thecorresponding alpha,β-diamino acid. Auxiliary cleavage inbasic conditions gave the water-soluble carboxylate diamine(9, Scheme 3). Boc deprotection in TFA proceeded cleanly(10); however, subsequent cyclization attempts usingMukaiyama’s reagent have yielded inconsistent results. Dif-ficulty purifying the water-soluble cyclization substrate aswell as the water sensitive nature of the cyclization mayexplain the unsuccessful results. Recent success in cleavageof the Boc group with the substrate still attached to the aux-iliary offers the possibility of a cleaner cyclization route.Continued work on this project will involve further explo-ration of cleavage methods and cyclization pathways as wellas diversification of possible Mannich adducts with a vari-ety of imine electrophiles. References1a The Antibiotic Alarm. Nature. 2013, 495, 141. 1b L.L. Silver, Clinical Microbiology Review. 2011,

24, 71-109.i J. Pitout, C. Sanders, E. Sander, J. Am. Med. 1997,

103, 51-59.ii W. Durkheimer, J. Blumbach, R. Lattrell, K. Sche-

unemann, Angew. Chem. Int. Ed. Engl. 1985, 24,180-202.

iii Thomas C. Richard, in Recent Progress in the

Chemical Synthesis of Antibiotics (Eds.: G. Lukacs,M. Ohno), 1990, pp. 534-564.

iv R. B. Sykes, D. P. Bonner, Reviews of Infectious Dis-eases, 1985, 7, S579-S593.

v M. J. Miller, P. G. Mattingly, M. A. Morrison, J. F.Kerwin, Jr, J. Am. Chem Soc. 1980, 102, 7026.

vi C. Hubschwerlen, G. Schmid , Helv. Chim. Acta.,1983, 66, 2206.

vii David J. Hart, Deok-Chan Ha, Chem. Rev. 1989,89, 1447-1465.

viii Thomas C. Richard, in Recent Progress in theChemical Synthesis of Antibiotics (Eds.: G. Lukacs,M. Ohno), 1990, pp. 534-564.

ix A. Iza, J. Vicario, L. Carrillo, D. Badia, Synthesis,2006, 23, 4065-4074.

x I. Abrahams, M. Motevalli, , A. Robinson, P. Wyatt,Tetrahedron, 1994, 50, 12755-12772.

xi I. B. Seiple, J. A. M. Mercer, R. J. Sussman, A. G.Manuscript in preperation.

xii A. G. Wenzel, E. N. Jacobsen, J. Am. Chem. Soc.2002, 124, 12964-12965. u


[*] C. S. H acknowledges the ACS for its financial supportthrough the NESACS Norris-Richards Research Scholar-ship.

Sukant TripathyAnnual MemorialSymposiumFriday, December 6, 20138 a.m. to 4:30 p.m.UMass Lowell Inn and Conference Center, 55 Warren St., Lowell, MA 01854Directions can be found in the ICC’s website: http://www.acc-umlinnandconferencecenter.com/maps-directions. The program includes talks by invited speakers and posterpresentations.Speakers:

E. Bryan Coughlin, University of MA AmherstAlan Dalton, University of Surrey, U.K.Jeremiah Johnson, MITChangshu Kuo, National Cheng Kung University, TaiwanRamanathan Nagarajan, U.S. Army NSRDECPrakash Rai, University of MA LowellTBA

Registration: Pre-Registration (FREE) is required byNovember 29, 2013 to [email protected] or 978-934-3695. Lunch and refreshments will be provided (soaccurate count is required). Please request vegetarian lunch-eon if preferred. u

http://www.acc-umlinnandconferencecenter.com/mapsdirections


(l-r) Morton Hoffman (Boston University), Elis-abeth Kapatsina (German Chemical Society),Mike Strem (Strem Chemicals).

Mike Strem (Strem Chemicals) at left with AlfredFlint (University of Rostock) at the Strem Chem-icals exhibitor booth.

Marinda Wu chatting with members of the German delegationafter the symposium: (l-r) Jens Breffke, Wilma Neumann, TorstenJohn, Susanne Leubner, Tanja Scholz, Martin Lichtenthaler,Andreas Seitz, Elisabeth Kapatsina. In background: Mike Neu-mann, Christian Weinberger.

Members of the German delegation and NESACS German Exchange Steering Com-mittee with Marinda Wu (ACS President), at center, after the symposium: (l-r) DeniseSchütz, Wilma Neumann, Torsten John, Jackie O'Neil, Mike Strem, Ruth Tanner, JensBreffke, Heidi Teng, Morton Hoffman, Anna Hofmann, Peter Sponholz, Martin Licht-enthaler, Mike Neumann, Christian Weinberger, Susanne Leubner, Stefan Zajonc,Tanja Scholz, Andreas Seitz, Elisabeth Kapatsina, Alfred Flint.

Members of the German delegation and the NESACS Steering Committee withfriends at the NERM dinner. (l-r) Seated: Rajeev Chorghade, Jackie O'Neil, MartinLichtenthaler, Elisabeth Kapatsina, Andreas Seitz, Keeve Gurkin; standing: PeterSponholz, Alfred Flint, Tanja Scholz, Jens Breffke, Susanne Leubner, Stefan Zajonc,Anna Hofmann, Denise Schütz, Heidi Teng, Mike Neumann, Christian Weinberger,Wilma Neumann, Torsten John.

Photos from the German Exchange atNERMPhotos by Morton Z. Hoffman

Updated frequently • Late-breaking news • Position PostingsBack issues of the Nucleus • Career-related Links • Awards and Scholarship

WWW.NESACS.org

Have you seen it on the NESACS website?

http://www.nesacs.org


Q. Exactly, how many awards andscholarships does NESACS sponsor?

A) One b) Two c) Many

www.nesacs.org/awards

Mike Neumann and Wilma Neumann discussAnna Hofmann's poster with her.

(l-r) Seated: Anna Hofmann, Jackie O'Neil,Wilma Neumann; standing: Peter Sponholz,Andreas Seitz

(l-r) Susanne Leubner, Heidi Teng, Tanja Scholz

Mike Strem (Strem Chemicals) at left with JensBreffke (Pennsylvania State University).

What’s Yours?Many local employers post positions

on the NESACS job board.

Find yours atwww.nesacs.org/jobs

NESACSArchivesHave MovedThe NESACS Archives were movedfrom their location of many years inthe basement of the Regis CollegeLibrary to a new temporary location atSigma-Aldrich Corporation in Natick,MA. A more permanent long-termstorage location is desired.

NESACS expresses great appreci-ation to Regis College for allowingNESACS to store its archives in itslibrary. NESACS is further apprecia-tive of Michael Singer and Sigma-Aldrich for making storage spaceavailable while a more permanentsolution is sought. u

German ExchangeContinued from page 10

Denise Schütz (University of Frankfurt), "Con-formational Flexibility of Toc34 HomodimerStudied by PELDOR."

http://www.nesacs.org/awards_main.html


transforming power of chemistry”) andmission (“Advance the broader chem-istry enterprise and its practitioners forthe benefit of Earth and its people”) ofthe ACS, the structure of the Society(local sections, technical divisions,committees, publications, staff, andvolunteers), and its core values (pas-sion for chemistry in the broadestsense, focus on members, professional-ism, diversity and inclusion). She thenexplored in detail the current strategicplan:• Provide information: Be the most

authoritative, comprehensive, andindispensable provider of chemistry-related information;

• Advance members careers: Empoweran inclusive community of members,with networks, opportunities,resources and skills to thrive in theglobal economy;

• Improve education: Foster the devel-opment of the most innovative, rele-vant, and effective chemistryeducation in the world;

• Communicate chemistry’s value:Communicate chemistry’s vital rolein addressing the world’s challengesto the public and policymakers.

After a question and answer period, theattendees mingled and spoke with Ms.Jacobs while enjoying a reception ofheavy hors d’oeuvres provided byJeannette Riley, Dean of the UMDCollege of Arts and Sciences.

Earlier in the day, Ms. Jacobs metwith members of the faculty and stu-dents in the Department of Chemistryand Biochemistry, toured the researchand teaching laboratories, and partici-

pated in the inauguration of the new400-MHz NMR facility.

Plans are now being developed forfurther events in SE-MA and an inau-gural one in NH during 2014. Modestfunds to support the program into thenext year were received by NESACSas an innovative project grant from theACS Local Sections Activities Com-mittee (LSAC). A survey of the atten-dees at the October 3rd event indicateda strong interest in future activities inSE-MA and a willingness of many tobecome actively involved. u

NESACS SE-MA EventContinued from page 4

Join NESACSon facebook

www.facebook.com/nesacs

inger of that institution as the GeneralChair. The Binghamton Section isexpected to submit a bid to hostNERM 2016 to celebrate its 75th

anniversary. The Central New Yorkand Rochester Sections have madeseparate expressions of interest forNERM 2017. NERM 2018 is currentlyopen; the Rhode Island Section willexplore the option for an Octobermeeting that year in Providence orNewport, perhaps in connection withthe Southeastern Massachusetts area ofNESACS.

The next meeting of the NERACSBoard will be at a 2014 National ACSmeeting, probably in San Francisco inAugust. u

NERACS ReportContinued from page 2

I was disappointed that StephenJay Gould’s memoir has not been writ-ten. His book “Wonderful Life” aboutall the strange and wonderful fossilizedcreatures discovered in the BurgessShale is one of my favorites.

The nuclear physicists involvedwith the creation of the atomic bombare well represented in the memoirs.Most recently the Philip Morrison andEdward Teller memoirs were publishedto join that of J. Robert Oppenheimer.

Albert Einstein is there along withThomas Edison. It is interesting to notethat Edison was not inducted until1927 when he was 80 years old. Iguess having a record number of USPatents was not sufficient for member-ship to the Academy until the sheervolume and economic impact over-whelmed the selectors. Notably, hismemoir was published in 1932 only ayear after his death.

There is an iPad application thatmakes accessing the memoirs verysimple. You will immediately see a tablisting of eighteen of the most recentlypublished memoirs. This tab is fol-lowed by a “featured” tab which is cur-rently honoring NAS Nobel Laureatessuch as Hans Bethe, Bruce Merrifield,and Theodore William Richards.

I highly recommend these mem-oirs as an informative and inspirationalwindow into the lives of these greatscientists. The NAS membershipincludes a rich selection of the mostinfluential scientists of the last 150years. These biographical memoirs area treasure. u

Biographical MemoirsContinued from page 7

Provost Karim

and development of a novel, potent,selective, and orally and CNS-penetra-ble H3R antagonist/ inverse agonist fortreatment of cognitive impairmentassociated with AD and Schizophrenia.This presentation will describe ourmedicinal chemistry efforts towardsthis goal, beginning with biologicalconcept through HTS and finally DCselection. u

AbstractContinued from page 5

THE COMMITTEE ONCHEMICAL ABSTRACTS(CCAS) WANTS YOUR

FEEDBACKVisit our page on ACS Network:

https://communities.acs.org/groups/chemical-abstracts-service-committee

or contact Michael Filosa with any suggestions at [email protected]

https://communities.acs.org/groups/chemical-abstracts-service-committee


• Hydrogen production and storage fora sustainable energy economy(organometallic chemistry and cataly-sis) – Peter Sponholz

• Research-experiencing learning in thestudent-based project “Make Sci-ence!” (chemical education) – StefanZajonc

• Applied gallium(I) chemistry: Syn-thesis of highly reactive polyisobuty-lene (organometallic chemistry andcatalysis) – Martin Lichtenthaler

• COX inhibitors with caraboranes aspharmacophore (medicinal chem-istry) – Wilma Neumann

• Synthesis, structure, and magneticproperties of tin-substituted ironnitrides SnxFe4-xN (poster) – TanjaScholz

• Novel phosphorous-carbon cages(poster) – Andreas Seitz

• Synthesis and evaluation of mannosederivatives as Pseudomonas aerugi-nosa lectin LacB antagonists (poster)– Anna Hofmann

• Influence of the surface ligand den-sity on the optical properties of semi-conductor nanocrystals (nanoscience)– Susanne Leubner

• Conformational flexibility of Toc34Homodimer studied by PELDOR(poster) – Denise Schütz

Accommodations at the Omni Hoteland registration at NERM, whichincluded participation in the welcomereception, social mixer, keynote dinnerwith Donna Nelson (University ofOklahoma), and awards dinner withMarinda Wu, were provided for theGerman delegation by NESACS. Aglobal innovation grant of $4,000 fromthe ACS International Activities Com-mittee partially covered thoseexpenses.

Attendees at the keynote dinnerhad the opportunity to hear Prof. Nel-son describe her activities as scientificadvisor to the popular television pro-gram, Breaking Bad, and to meet herpersonally. Honored at the awards din-ner was Sharon Palmer, a chemistryteacher at Amherst (MA) Regional

High School, who received the 2013ACS Division of Chemical EducationNortheast Region Award for Excel-lence in High School Teaching.

Closer to home, also honored atthe awards dinner was Doris Lewis(Suffolk University), who received the2013 E. Ann Nalley Northeast RegionAward for Volunteer Service to theACS for her activities with the multi-award-winning student chapter at herinstitution, with NESACS as sectionchair, leader in the creation of Connec-tions to Chemistry and the Phyllis A.Brauner Memorial Lectures, and chairof the Government Affairs Committee,and at the national level with the ACS

Committee on Chemistry and PublicAffairs and the Committee on PublicRelations and Communications.

There will be no NortheastRegional Meeting in 2014. The nextNERM will be held in Ithaca, NY, onJune 10-13, 2015, on the campus ofIthaca College; Akiko Fillinger of thatinstitution will serve as the GeneralChair. The plenary speaker will beEsther Takeuchi (SUNY Stony Brook),who received the 2013 E.V. MurphreeAward in Industrial and EngineeringChemistry from the ACS for her inno-vative work on advanced batterypower sources. u

NERM 2013 ReportContinued from page 6

Donna Nelson (University of Oklahoma), scien-tific advisor for Breaking Bad, at left with RuthTanner (University of Massachusetts Lowell),NESACS Immediate Past Chair.

(l-r) Sandy Hoffman, Marinda Wu (ACS Presi-dent), Doris Lewis (Suffolk University), Kath-leen Schulz (ACS Director-at-Large), JulieSmist (NERACS Chair), Dorothy Phillips(NESACS Councilor).

Mukund Chorghade (Thinq Pharma) with hiswife, Veena, and son Rajeev (Carnegie MellonUniversity).

Ken White (NERM General Co-Chair) at leftreceiving a plaque of recognition from TomGilbert (ACS District I Director).

Photos from the NortheastRegional MeetingOctober 23-26, 2013, New Haven, ConnecticutPhotos by Morton Z. Hoffman


B U S I N E S S D I R E C T O R Y

SERVICESSERVICESSERVICES


CAREER SERVICESSERVICES

B U S I N E S S D I R E C T O R Y

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Index of AdvertisersEastern Scientific Co. ......11Mass-Vac, Inc.....................4Micron, Inc. .....................14NuMega Resonance Labs14Organix, Inc. ....................14PCI Synthesis...................14Rilas Technologies, Inc. ..15Robertson Microlit Labs..14Tyger Scientific, Inc. .......14Tyger Scientific ...............14VACUUBRAND .............15Waters Corporation..........15

Check the NESACS home pagefor late Calendar additions:http://www.NESACS.orgNote also the Chemistry Department webpages for travel directions and updates.These include:http://www.bc.edu/schools/cas/chemistry/semina

rs.htmlhttp://www.bu.edu/chemistry/seminars/http://www.brandeis.edu/departments/chemistry/

events/index.htmlhttp://www.chem.harvard.edu/courses/seminars.

phphttp://chemcalendar.mit.edu/index.phphttp://chem.tufts.edu/seminars.htmlhttp://engineering.tufts.edu/chbe/newsEvents/se

minarSeries/index.asphttp://www.chem.umb.eduhttp://www.umassd.edu/cas/chemistry/http://www.uml.edu/Sciences/chemistry/Seminar

s-and-Colloquia.aspxhttp://www.unh.edu/chemistry/events

Dec 02Prof. Jeffrey Long (U.C. Berkeley)Harvard University, Pfizer Hall4:15 pm

Dec 03Prof. Bing Xu (Brandeis University)“Exploring Molecular Nanomaterials in CellularEnvironments”Tufts U., Pearson P-106, 4:30 pmProf/ Yan Jessie Zhangm (U. of Texas-Austin)Boston College, Merkert 1304:00 pmProf. Jonathan Rochford (UMass-Boston)U. New Hampshire, Room N104 (L103)11:10 am

Dec 04Prof. Joel Rosenthal (U. of Delaware) UMass Dartmouth, Dion Building-Rm 1154:00 pm

Dec 05Prof. Sanjay Mathur, (U. of Cologne)Boston College, Merkert 130 4:00 pm

Dec 06Sukant Tripathy Memorial Symposium 2013UMass Lowell Inn and Conference Center55 Warren St., Lowell, MA 018548 am to 4:30 pmPre-registration is required. Contact:[email protected] 978-934-3695

Dec 09Prof. Joseph Sadighi, (Georgia Tech)“Small Clusters of Group 11 Metals SupportedBy N-Heterocyclic Carbenes”Brandeis, Gerstenzang 1214:00 pmProf. Eun Suk Kim (Brown University)Boston University, Metcalf Rm 113 4:00 pm

Dec 11Physical Chemistry SeminarProf. John Tully (Yale University)MIT, Rm 4-2314:00 pm

Dec 18Physical Chemistry SeminarProf. Adam Willard (MIT)Boston University, Metcalf Rm SCI5122:00 pm

Notices for The NucleusCalendar of Seminars should be sent to:Michael Filosa, email:Michael.filosa(at)verizon.net u

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A Plea forLocalSectionDuesWhen you receive your dues bill fromNational ACS it will include an itemfor Northeastern LS Voluntary Dues of$22. Every member of ACS who livesin New Hampshire or eastern Massa-chusetts is automatically a member ofthe Northeastern Section (NESACS).These dues are voluntary, and abouthalf of our 6500 members choose notto pay them.

As Treasurer of NESACS, I wouldlike to urge all members to pay thesedues and support the Section activities,even if you do not regularly attendNESACS meetings. Dues constitutethe major source of discretionaryincome to the Section. While mostawards programs are supported byTrust funds, your dues and contribu-tions fund activities such as those ofthe Education Committee, NationalChemistry Week, Younger Chemists,and Project SEED, all of which benefitthe general chemical community.

Non-payment of Local Sectiondues has no effect on the individualmember. ACS does not permit us todiscriminate between members whopay dues and those who do not, so, forexample, the Nucleus is sent to allmembers by mail or electronically.Members for whom dues are non-deductible might prefer to send a con-tribution to NESACS, sincecontributions to the Section are taxdeductible. Checks payable toNESACS can be sent to the Treasurerat 19 Mill Rd., Harvard, MA 01451 orto the administrative secretary.

Your support of the Section isgreatly appreciated, and the Board ofDirectors conscientiously strives to seethat all Section activities advance thechemical enterprise.-Jim Piper, NESACS Treasurer u

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Documents

from NERM Memoirs€¦ · 2 The Nucleus December 2013 The Board of Directors of the North - east Region of the ACS, Inc. (NER - ACS) met on Saturday, October 26, 2013, in the Omni