1. January 2015
Daniel Romo, Professor & Director of the Natural Products LINCHPIN Laboratory
[***Moving to Baylor University, August 2015***]
Synthetic, Biomechanistic, and Biosynthetic Studies of Bioactive Natural Products (Chemical
Biology); Asymmetric Synthesis, Novel Transformations, and Applications of β-Lactones
(Synthetic Methodology); Natural Product Mode of Action Studies (Chemical Genetics)
Rm 304, (979) 845-9571, "romo@tamu.edu", FAX (979) 862-4880; WEB page:
http://www.chem.tamu.edu/rgroup/romo
At the heart of our research interests is the chemistry and biology of natural products. These are unique and
often structurally complex molecules that are designed to interact in highly specific ways with various cellular
receptors and by homology those found in humans.
Thus, all our projects begin with natural products
encompassing development of novel synthetic
strategies towards these naturally occurring
compounds or derivatives that in turn serve as useful
leads for inquiries into cell biology.
‘Bioactivity-guided Retrosynthesis.’ This is a new
approach toward the pursuit of natural product total
synthesis that enables a synthetic chemist, if
interested, to get involved with MS-based methods
for activity based proteomic profiling at the early
stages of the total synthesis effort. Natural products
in this category that are currently being pursued include oxazolomycin and the gracillins. (No papers in this
area yet, however we are preparing our initial paper that describes this new strategy for total synthesis. In
addition, our recently described Diels-Alder Lactonization organocascade is being applied to the gracillins.
Thus, we attempt to make use of our methodology to access natural products that we in fact plan to pursue
further in terms of biological studies. In this case, toward activity based proteomic profiling with these
electrophilic natural products and as a further application of bioactivity-guided retrosynthesis. Biological
studies of the gracillins and
spongiolactone/oxaxolomycin are
supported by excellent collaborations
with Prof. Luis Botana (Spain) and Prof.
Stephan Sieber (Germany), respectively.
Exploiting the potential of chiral
unsaturated acylammonium salts. We
recently discovered and are continuing to
mine the rich potential of this readily
available chiral intermediate readily
derived from commercially available acid
chlorides and catalysts. Numerous other
organocascade processes are waiting to be
discovered that make full use of the triple
reactivity of this versatile intermediate!
Computational studies in collaboration
with Prof. Dean Tantillo (UC Davis) and
mechanistic studies (e.g. In situ IR, LC-
MS) are being pursued in conjunction
with our methodological studies. •Mass
Spectrometry Based-Profiling of the
Cancer Proteome with Anticancer Natural Products. Using numerous cancer cell lysates that are now
commercially available, we will study the interactions of several, putative natural product-based covalent
modifiers of cellular proteins that are being synthesized in the lab. These in vitro experiments will provide
initial data regarding protein targets of these natural products. Further experiments to validate these targets
including the use of isotopically labelled proteomes (SILAC) and over-expression of putative targets in cell
lines will be conducted in the laboratories of collaborators and students would have the opportunity to visit
for short stays (e.g. with Prof. Jun Liu, Johns Hopkins University, Dept. of Pharmacology or Prof. Stephan
Graduate Students Christian Chalheine
Mikail Abbasov Weixu Kong
Natalie Harvey
Khoi Van
Yongfeng Tao
Post-Doctoral Students
Dr. Paul Gladen
Dr. Morgan Jounneau
Dr. Sreekumar Vellalath
LINCHPIN Lab: Dr. Ken Hull (co-Director)
Dr. Mingzhao Zhu
Dr. Haoran Xu
Dr. Omar Robles
TAMU Undergrad MiniPharma
Protein Conjugation Group: Wali Kahn
(Group and Team Ldr), Lorna Min;
Molecular Modeling Team: Emily
Brackhahn (Group Ldr), Asuka Orr, Adam
Burkhard; Synthesis: Julia
Taylor (Team Ldr), Kacey Ortiz
Fungal Group: Jennifer
Cuaderes (Group Ldr); Hannah
Bolton, Lauren Davis (intern).
N
N
H
N
N
H2N
O
N
HN
Cl
NH2
H
H2N
palau'amine
HO
N
NH
HN
HN
Cl
OH
NHR
MeO
HN
NH
NHR
axinellamine D
(R = 2,3-dibromoacylpyrrole)
H
H
H
O
H
O
H O
H
OH
CO2Me
H
H
OH
rameswaralide
•anti-inflammatory
agelastatin A
•Antitumor/cytotoxic agent
N
O
Me
H
OH OMe
H
N
MeO Me
OH
O
Me Me Me
N
O
OH
oxazolomycin A
O
scabrolide A
O
H
O
OH
H
Me
O
O
H
H
H
Me
OH
H
MeHO
O
H
Me
O
O
H
zedoarondiol H
Me
OMe
H
HO
HO
Me
O
O
chinesin II
N
NH
O O
O
H
N
ONH
HO
O
HO
O
O
O
N
NH2
NH2
O
O
HO
suomilide
O
OCH3
O3SO
Current Natural Product Topics (Synthesis and Biology) in the Romo Group
R =
H
N
O
Br
Br
O
H
OC(O)CH2CH(CH3)2
spongiolactone
O
caulolactone A
•antitumor/antibiotic
Me
O
H
H
OAc
Me
Me Me
OAc
gracilin A
N
NH
NH
N O
Me
HO
Br
O
H
H H
Me
Me Me
O
H
H
O
O
OAc
H
Me
tetrahydroaplysulphurin-1

2. Sieber, Tech. Univ. of Munich, Germany, or with Prof. Ben Cravatt, Scripps, CA). Molecular level mode of
action studies of natural products. We bring to bear the full range of organic methods including microscale
derivatizations developed in our group (with microscale purification and characterization enabled by a new
Bruker LC-SPE-NMR) and total synthesis to fully understand the mechanism of action of a bioactive natural
product including detailed structure-activity relationships and the use of either affinity chromatography or
activity-based proteomic profiling. Current pursuits in this area include rameswaralide, ophiobolin, and
agelastatin A (all nanomolar inhibitors of various cancer cell lines). These studies are greatly bolstered by
interactions with scientists working in the Natural Products LINCHPIN Laboratory and a fruitful long term
collaboration with Jun Liu (Johns Hopkins) and more recent collaboration with Prof. Alex Kornienko (Texas
State U.). Natural Products LINCPHIN Laboratory. This Collaboration Center is focused on the application of
strategies being developed in our group to more rapidly couple a natural product with its cellular protein
target. In addition LINCHPIN scientists assist in translating novel drug leads to therapeutic lead compounds
and diagnostics by assistance with scale-up and further SAR studies. Importantly, students in my group
interact frequently with research scientists in this laboratory including co-Director, Dr. Ken Hull, who has >20
years pharma experience.
SELECTED RECENT PUBLICATIONS (out of 114)
Stout, E. P.; Wang, Y.-G.; Romo, D.; Molinski, T. F. “Pyrrole-Aminoimidazole Alkaloid Metabiosynthesis with
Marine Sponges Agelas Conifera and Stylissa Caribica” Angew. Chem. Int. Ed. 2012, 51, 4877.
Reyes, J.C.P.; Romo, D. “Bioinspired Total Synthesis of AgelastatinA” Angew. Chem. Int. Ed. 2012, 51, 6870.
(Highlighted in Synfacts 2012)
J. Li, J. S. Cisar, C. Zhou, B. Vera, H. Williams, A. D. Rodríguez, B. F. Cravatt, and D. Romo. “Simultaneous
structure-activity studies and arming of natural products via CH amination reveal the cellular targets of
eupalmerin acetate” Nature Chem. 2013, 5, 510-517.
G. Liu, M. A. Shirley, K. N. Van, R. McFarlin, D. Romo “Rapid Assembly of Complex Cyclopentanes
Employing Chiral, α,β−Unsaturated Acyl Ammonium Intermediates” Nature Chem. 2013, 5, 1049-1057.
(Highlighted in Chem. Eng. News, BioNews Texas, and Synform.)
S. Vellalath, K. N. Van, D. Romo “Direct Catalytic Asymmetric Synthesis of N-Heterocycles from
Commodity Acid Chlorides Employing α,β-Unsaturated Acylammonium Salts” Angew. Chem. Int. Ed. 2013,
52, 13688-13692. (Highlighted in Synfacts 2013, twice!)
Abbasov, M.E.; Hudson, B.M.; Tantillo, D.J.; Romo, D. “Acylammonium Salts as Dienophiles in Diels-Alder-
Lactonization Organocascades” J. Am. Chem. Soc. 2014, 136, 4492-4495. (Featured in JACS Highlights, Synfacts
2014, Advances in Engineering)
Harvey, N. L.; Krysiak, J.; Chamni, S.; Cho, S. W.; Sieber, S. A.; Romo, D. “Synthesis of (±)-Spongiolactone
Enabling Discovery of a More Potent Derivative” Eur. J. Chem. 2014, on-line.
CURRENT POSITIONS OF FORMER GROUP MEMBERS
Graduate Students (20 Ph.D.; 5 M.S.): Dr. Robert M. Rzasa (PhD, 1998): Amgen, Thousand Oaks, CA; Dr. William Schmitz
(PhD, 1998): Bristol-Myers-Squibb, Wallingford, CT; Dr. Hong Woon Yang (PhD, 1998): GlycoMimetics, Gaithersburg, MD: OK;
Dr. Cunxiang Zhao (PhD 1999): Kalypsys, Inc., San Diego, CA; Stephen Cohn (MS, 1999); Ingrid Buchler (MS, 2000); Reginald
Tennyson (MS, 2001): Encysive Inc.; Dr. Yingcai Wang (PhD, 2002) Res. Prof. Purdue, USA; Dr. Anja Dilley (PhD 2002); Dr.
Karine Poullennec (PhD 2003), Selcia Inc., UK; Min Zhou (MS, 2003); Francisco Franco-Torres (MS, 2007); Dr. Ke Kong (Ph.D
2007), Post-doc w/John Wood, Colorado State Univ., Res. Scientist, Amgen, Thousand Oaks, USA; Dr. Richard Duffy (PhD 2007),
Post-doc w/Mike Doyle, University of Maryland; Dr. Shaohui Wang, (PhD 2007), BeiGene, Beijing, China; Dr. Andrew T. Mitchell
(Ph.D. 2008), Asst. Prof., Illinois State Univ.; Dr. Sungwook Cho (Ph.D. 2007), Samsung, Korea; Andrea Matla (MS, 2008),
Teacher, Houston, TX; Dr. Vikram Purohit (Ph.D. 2008), TEVA, Malvern, PA; Dr. Kay Morris (Ph.D. 2010), Haliburton, Houston,
TX, USA; Dr. Changsuk Lee (Ph.D. 2009) Post-doc, Texas Christian Univ.; Dr. Manuel Zancanella (Ph.D. 2010), Amgen Inc., San
Francisco, CA, USA; Dr. Supakarn Chamni (Ph.D. 2011), Asst. Prof., Chulalongkorn Univ., Thailand; Dr. Gang Liu (Ph.D. 2011)
Res. Scientist, M.D. Anderson Cancer Center, Houston, TX. Dr. Morgan E. Shirley (Ph.D. 2013) Res. Scientist, Chevron, San
Francisco, CA.
Romo Group
Chemistry
Highlighted
On Cover Art