EdgeRank: Co zrobić, by Facebook polubił Twoje posty? (handout)
Romo 1 page res handout 1_2015
2
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, "[email protected]", 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 H 2 N O N HN Cl NH 2 H H 2 N 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 CO 2 Me H H OH rameswaralide •anti-inflammatory agelastatin A •Antitumor/cytotoxic agent N O Me H OH O Me 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 Me HO 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 O NH HO O HO O O O N NH 2 NH 2 O O HO suomilide O OCH 3 O 3 SO Current Natural Product Topics (Synthesis and Biology) in the Romo Group R = H N O Br Br O H OC(O)CH 2 CH(CH 3 ) 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
-
Upload
daniel-romo -
Category
Documents
-
view
132 -
download
0
Transcript of Romo 1 page res handout 1_2015
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, "[email protected]", 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
HN
NH2N
ON
HN
Cl NH2
H
H2N
palau'amine
HO
NNH
HN
HN
Cl
OH
NHRMeO
HN
NH
NHRaxinellamine D
(R = 2,3-dibromoacylpyrrole)
HH
H
O
H
O
H O
H
OHCO2Me
H
H
OH
rameswaralide•anti-inflammatory
agelastatin A•Antitumor/cytotoxic agent
NOMe
H
OH OMeHN
MeO Me
OH
O
Me Me MeN
O
OHoxazolomycin A
O
scabrolide A
O
H
O
OHH
MeO
OH
H
H
Me OH
H
MeHO
O
H
MeO
O
H
zedoarondiol H
MeOMe
HHO
HOMe
O
O
chinesin II
NNH
O O
O
HN
ONH
HO
OHO
OO
O
N
NH2
NH2
O
O
HO
suomilide
O
OCH3
O3SO
Current Natural Product Topics (Synthesis and Biology) in the Romo Group
R =HN
OBr
Br
O
HOC(O)CH2CH(CH3)2
spongiolactone
Ocaulolactone A
•antitumor/antibiotic
Me
O
H
H
OAc
Me
Me Me
OAc
gracilin A
NNH
NH
N OMe
HOBr
O
H
H H
Me
Me Me
O
H
HO
O
OAc
HMe
tetrahydroaplysulphurin-1
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
