Ivan Perez

Department of Chemistry, Boston University

590 Commonwealth Ave, Boston, MA 02215
Cell: 347-445-8049 E-mail: iperezbu@bu.edu
Education:
May 2014 Bachelor of Science in Chemistry
Boston University, Massachusetts, USA
Research Experience:
September 2012- Undergraduate Research Assistant
Department of Chemistry
Boston University, Boston, MA
P.I.: Professor Aaron Beeler
June 2012- Visiting Scholar
August 2012 Department of Chemistry
Brooklyn College, Brooklyn, NY
P.I.: Professor Maria Contel
September 2011- Undergraduate Research Assistant
February 2012 Department of Chemistry
Boston University, Boston, MA
P.I.: Professor Scott Schaus
Work Experience:
September 2011- On Campus Grader
Department of Mathematics
Boston University, Boston, MA
Presentations:
August 2013 Initial Probing into Mechanism of Action of PrP
Sc
Proliferation
Inhibitor.; Perez, I.; Heeres, J.; Harris, D.; Beeler, A.; Undergraduate
Research Symposium, Boston University, Boston, MA.
Honors and Awards:
January 2013 Undergraduate Research Opportunity Program Faculty Matching Grant
May 2013 Undergraduate Research Opportunity Program Student Research Award
References:
Prof. Aaron B. BeelerUndergraduate P.I. Assistant Professor of Chemistry at Boston University
(beelera@bu.edu, 617-358-3487)
Oscar J. InghamData analyst at Pfizer
(ojingham@gmail.com)
Dr. Kristen MascallPost Doctoral Fellow at Boston University
(kmascall@bu.edu)
Research Summary (Ivan Perez)
Undergraduate Studies
Chemistry Department, Boston University, MA
P.I.: Professor Aaron B. Beeler
1. Synthesis of LD49 pull-down probes
Creutzfeldt-Jakob disease and other
spongiform encephalopathies are caused by
infectious prion proteins.
1
The Harris Group at
Boston University Medical Campus (BUMC) found
LD49 1a using a high-throughput phenotypic
screen. LD49 was to shown to inhibit and reverse
the aggregation process of PrP
Sc
, the infectious
isoform of PrP
C
, in transfected cells. Our goal is to
synthesize tagged analogs for target identification.
Specifically perfluorooctylethyl (fluorous) and
biotin analogues synthesized.
N
N
N
N
Ph
N
N
O
N
O
H
N
O
C
8
F
17
HN
O
H
NH
H S
O
1a
1b
1c
0.322M
0.294M
>50M
Parent LD-49 Scaffold
Following the resynthesis of 1a for target
validation, a synthesis of a biotin conjugate 1c was
developed. However the CR-HEK viability assay
(analogous assay to the original LD49 high
throughput assay) showed little phenotypic activity.
Efforts towards smaller and further removed tagged
analogs were developed.
The fluorous conjugate 1b developed held
activity in the CR-HEK assays and was
subsequently used for pull-down assays. Because of
the relatively low potency of the molecule pull-
down isolation of target proteins has not been
successful. As a result second generation pull-down
probes were investigated.
Beeler and Harris hypothesized that based
on structural similarities of known LD49
2

1

inhibitors that the
2

1
subunit was a prominent
target. Further investigation was conducted by
synthesizing known
2

1
inhibitors (2a-c, 3a).
3-5

Compounds in the set showed high activity
which further indicated that
2

1
was likely a target.
The Stearns ligand 3a showed exceptional potency.
Its core structure was used as the pharmacophore
towards the synthesis of directly linked PEG-2
spaced biotin and fluorous analogues. Compounds
3b and 3c are currently being tested for their
activity in the phenotypic assay relative to the
original Stearns compound.
N
N
N
N
Ph
N
N
N Ph
HN
Ph
N
N NH
2a 2b 2c 3a
50M 91nM 5M 5M

1
scaffold
3
O
HN
O
H
NH
H
S
O
O
O
H
N
C
8
F
17
H
N
O
H
N
H
N
O
C
8
F
17
H
N
O
H
N
O
HN
O
H
NH
H
S
N
N
N Ph
NH
3b
3c
3d
3e
2
2
Stearns-Scaffold
Alternative methods towards target
identification applied are DARTS (Drug Affinity
Responsive Target Stability), in addition to pull-
down methods. Future medicinal chemistry
applications include the construction of a SAR
library of Stearns scaffolds outlined with a readily
accessible tunable synthesis.
5

R
1
OEt
O O
R
2
O
X
NH
2
Ph
Ph
N
R
2
O
EtO
R
1
N
HN
N
R
2
R
1
Ph
R
3
O
N
N
N
R
2
R
1
Ph
R
3
NR
4
R
5
1. SnCl
4
R
3
Cl
O
2. N
2
H
4
1. POCl
3
2. NHR
4
R
5
1.
2.
[1] Belay, E. Annu. Rev. Microbiol., 1999, 53, 283-314
[2] Harris, D.A. Prion, 2011, 6, 40-45
[3] Myatt, J.W. Bioorg. Med. Chem. Lett., 2010, 20, 4683-4688
[4] Thompson, L.R. Bioorg Med Chem Lett., 2011, 21, 3764-3766
[5] Stearns, B.A. Bioorg. Med. Chem.Lett., 2004, 14, 1295-1298
Chemistry Department, Brooklyn College, NY
P.I.: Professor Maria Contel
2. Synthesis of heterometallic imino-phosphorane
cyclopalladates
Organometallic chemistrys role in the
development of anti-tumor agents has largely been
dominated by cisplatin-type chemotherapeutics.
6

Research in Contel group focuses on the synthesis
of heterometallic compounds for the advent of cost-
effective chemotherapeutics and a potential for non-
cisplatin type activity in organometallic antitumor
agents.
O
Pd N
Br
P
N
N
N
O
N
P
N
N
N
Pd
O
O
P
N
Ph
Pd
O
O
Ph
Fe
P
N
Ph
Pd
Br
Ph
Fe
2
2
Jurkat IC
50
: 8.10M
PBMC IC
50
: 209 M
DU-145 IC
50
: 49.3M
Jurkat IC
50
: 10.5M
PBMC IC
50
: 118 M
DU-145 IC
50
: 96.2M
4a 4b 5a 5b
Previous work from Contel showed that
imino-phosphorane palladium complexes had IC
50
s
on par with cisplatin in Jurkat and DU-145 cell lines
while showing lower IC
50
's in cisplatin resistant
PBMC the cell line.
7
Ferrocene imino-phosphorane
cyclopalladates 4b and 5b were of special interest to
the group because their heterometallic nature has
been shown to mimic polynuclear enzymes found in
nature which can potentially lead to unique
enzymatic or biological activity.
8
PhN
3
Fe
PPh
2
Fe
PPh
2
N
Ph
Fe
P
N
Ph
Pd
Br
Ph
Fe
2
P
N
Ph
Pd
O
O
Ph
Fe
PPh
2
Cl
AlCl
3
Th(acac)
2
Pd(OAc)
2
6 7 8
4b 5b
42% overall
Cyclopalladates were prepared in four steps
in 42% yield. Key steps included cyclopalladation
with Pd(OAc)
2
and dimer 4b cleavage with
Th(acac)
2
to afford 5b. Future biological
applications of Heterocyclic cyclopalladate ligands
include cytotoxicity testing on cisplatin-resistant
cell lines.
[6] Farrell, N. Uses of Inorganic Chemistry in Medicine, Royal
Society of ChemistryCambridge, 1999.
[7] Contel, M. Organometallics, 2012, 31, 5772-5781
[8] Jaouen, G. J. Med.Chem., 1992, 35, 3130.
Chemistry Department, Boston University, MA
P.I.: Professor Scott E. Schaus
3. Methodology development of Enantioselective 1,4-
Conjugate Addition by Chiral Phosphoric acid
Catalysis
Total synthesis of natural products in the
comunesin/nomofungin family has driven much
interest for the development of new asymmetric
synthesis techniques.
9
Fundamental methodology of
an asymmetric 1,4 conjugate addition(ACA) was
imperative for facile accession to the nomofungin
tetracyclic core 9 (highlighted in red).

N
Me
O
N
N
O
O H
H
O
O
P
9 10
R
R
R=H, Br, t-Bu
O
OH
3,3-Phosphoric acid catalysts 10 were
accessible from 3,3-bromo-BINOL in three steps
and were functionalizable through standard
organolithium alkylations.
10
A bench stable ortho-
quinonemethide (o-QM) 14 was accessed in 5 steps
in 7% yield from sesamol 11.
11
HO
O
O
HO
O
O
O
Ph
HO
O
O
Ph
14
11
12
13
2. PhCHO, KOH, EtOH
1. Ac
2
O,BF
3
OEt
2
2. NaBH
4
, THF
1. ClCO
2
Et, Et
3
N Ag
2
O
Et
2
O
O
O
Ph
O
O
O
Ph
NMe
H
OH
N
Me
10 (10mol%)
CH
2
Cl
2
, -78

C, 6h
14
15
Results were inconclusive of whether an ACA
was feasible on an o-QM system. The use of hydrogen
bonding catalyst and potential -stacking are clever
catalyst designs. Further modifications include tuning
the electronics around the biaryl portion to induce
favorable -stacking interactions with the substrate.
[9] Mulzer, J. Angew. Chem. Int. Ed. 2008, 47, 8170 8176
[10] Lin, P. J. Org. Chem. 2009, 74, 86818689
[11] Lectka, T. Org. Lett., 2008, 10, 4951-4953