Thomas Minehan

EDUCATION

B.A., Columbia University, 1992
Ph.D., Harvard University, 1998

POSTDOCTORAL APPOINTMENT

California Institute of Technology, 1999-2001

COURSES TAUGHT

Chemistry 102, General Chemistry II
Chemistry 333, Organic Chemistry I
Chemistry 334, Organic Chemistry II
Chemistry 411, Synthesis
Chemistry 531, Survey of Organic Reactions
Chemistry 534, Advanced Organic Chemistry
Chemistry 564, Bioorganic Chemistry

RESEARCH INTERESTS

Organic Chemistry
Research in the Minehan lab is directed toward three principal areas: the development of new synthetic methodologies for carbon-carbon bond formation, the total synthesis of biologically and medicinally relevant natural products, and the exploration of new molecular scaffolds for the sequence-specific recognition of DNA. Synthetic methodology projects explore the ability of ynol ethers to engage in tandem inter- and intramolecular reactions with electrophiles and nucleophiles, allowing multiple new carbon-carbon and carbon-heteroatom bonds and stereogenic centers to be formed in a single step. Ynol ethers are very useful functional groups for the rapid increase of molecular complexity in chemical synthesis. We are also engaged in the total synthesis of natural products from the polyketide, C-arylglycoside, and sesquiterpene families of natural products, whose significant biological activities, especially with respect to tumor cells and cancerous tissues, merits further study. In connection with this work, since many of the natural products being prepared in our lab are known to interact with nucleic acids, we are also engaged in studying the binding mode, binding affinity, and sequence selectivity of these compounds for DNA by fluorescence spectroscopy, circular dichroism, and isothermal titration calorimetry. From this work we hope to develop a paradigm for the binding of nucleic acids by small molecules which allows specific DNA sequence and groove targeting (major vs. minor). Since the vast majority of DNA-binding regulatory proteins associate with the major groove of DNA, we are particularly interested in designing small molecules to interact with the major-groove of DNA in a shape-selective fashion.

REPRESENTATIVE PUBLICATIONS

1. "Total Synthesis of Alvaradoins E and F, Uveoside, and 10-epi-Uveoside” Ng, K.; Shaktah, R.; Vardanyan, L.; Minehan, T.G. Org. Lett. (2019), 21, 9175-9178.
2. “Synthesis and DNA Binding Profile of Monomeric, Dimeric, and Trimeric Derivatives of Crystal Violet” Nunez, O.; Chavez, B.; Shaktah, R.; Pereda Garcia, P.; Minehan, T.G. Bioorg. Chem. (2019), 83, 297-302.
3. “Ring Expansion, Ring Contraction, and Annulation Reactions of Allylic Phosphonates under Oxidative Cleavage Conditions” Orr, D.; Yousefi, N; Minehan, T.G. Org. Lett. (2018), 20, 2839-2843.
4. “Dimeric and Trimeric Derivatives of the Azinomycin B Chromophore show Enhanced DNA Binding” Balazy, M.; Fausto, A.; Voskanian, C.; Chavez, B.; Panesar, H.; Minehan, T.G. Org. Biomol. Chem. (2017), 15, 4522-4526.
5. “A Protecting-Group Free Synthesis of (-)-Hortonones A-C from the Inhoffen-Lythgoe Diol” Stambulyan, H.; Minehan, T.G. Org. Biomol. Chem. (2016), 14, 8728-8731.
6. “A Single-Flask Synthesis of Morita–Baylis–Hillman Adducts from Ethoxyacetylene and Carbonyl Compounds: Synthesis of Subamolides D and E” Ng, K.; Minehan, T.G. Org. Lett. (2016), 18, 4028-4031.
7. “Tandem Carbon-Carbon Bond-Forming Reactions of 1-Alkynyl ethers” Minehan, T.G. Acc. Chem. Res. (2016), 49, 1168-1181.
8. "A single-​flask synthesis of α-​alkylidene and α-​benzylidene lactones from ethoxyacetylene, epoxides​/oxetanes, and carbonyl compounds" Ng, K.; Tran, V.; Minehan, T. Tetrahedron Lett. (2016), 57, 415-419.
9. “Synthesis and DNA binding profile of N-​mono- and N,​N'-​disubstituted indolo[3,​2-​b]​carbazoles” Panesar, H.; Solano, J.; Minehan, T.G.  Org. Biomol. Chem. (2015), 13, 2879-2883.
10. "Total synthesis of polycarcin V and evaluation of its DNA-binding profile” Cai, X.; Ng, K.; Panesar, H.; Moon, S.-J.; Paredes, M.; Ishida, K.; Hertweck, C.; Minehan, T.G. Org. Lett. (2014), 16, 2962–2965.
11. “Synthesis of 3,3’-di-O-methyl ardimerin and exploration of its DNA binding properties” Mavlan, M.; Panesar, H.; Yepremyan, A.; Minehan T.G. Org. Lett. (2014), 16, 2212-2215.
12. "Low-Temperature n-Butyllithium-Induced [3,3]-Sigmatropic Rearrangement/ Electrophile Trapping Reactions of Allyl-1,1-Dichlorovinyl Ethers. Synthesis of beta-, gamma- and delta-lactones" Christopher, A.; Brandes, D.; Kelly, S.; Minehan, T.G. Org. Biomol. Chem. (2013), 11, 7658-7661.
13. "Anti-Peroxyl Radical Quality and Antibacterial Properties of Rooibos Infusions and Their Pure Glycosylated Polyphenolic Constituents" Simpson, M.J.; Hjelmqvist, D.; Karamehmedovic, N.; Minehan, T.G.; Yepremyan, A.; Salehani, B.; Lissi, E.; Joubert, E. Udekwu, K.I.; Alarcon, E.I. Molecules (2013), 18, 11264-11280. 
14. "Lewis-acid catalyzed intramolecular condensation of ynol ether-acetals. Synthesis of alkoxycycloalkene carboxylates" Tran, V.; Minehan, T.G. Org. Lett. (2012), 14, 6100-6103. 
15. "Total Synthesis of Indole-3-acetonitrile-4-methoxy-2-C-beta-D-gluco-pyranoside. Proposal for structural revision of the natural product" Yepremyan, A.; Minehan, T.G. Org. Biomol. Chem. (2012), 10, 5194-5196. 
16. "Intramolecular [2 + 2] Cycloaddition Reactions of Alkynyl Ether Derived Ketenes. A Convenient Synthesis of Donor–Acceptor Cyclobutanes" Tran, V.; Minehan, T.G. Org. Lett. (2011), 13, 6588-6591. 
17. "[3,3]-Sigmatropic Rearrangement/5-Exo-Dig Cyclization Reactions of Benzyl Alkynyl Ethers: Synthesis of Substituted 2-Indanones and Indenes" Tudjarian, A.A.; Minehan, T.G. J. Org. Chem. (2011), 76, 3576-3581. 
18. "Indium-Mediated Allylation of Aldehydes, Ketones, and Sulfonimines with 2-(Alkoxy)allyl bromides" Dhanjee, H.; Minehan, T.G. Tetradehron Lett. (2010), 51, 5609-5612. 
19. "Concise Total Syntheses of Aspalathin and Nothofagin" Yepremyan, A.; Salehani, B.; Minehan, T. G. Org. Lett. (2010), 12, 1580-1583. 
20. "A Sequential Indium-Mediated Aldehyde Allylation/Palladium-Catalyzed Cross-Coupling Reaction in the Synthesis of 2-Deoxy-?-C-Aryl Glycosides" Moral, J. A.; Moon, S. -J.; Rodriguez-Torres, S.; Minehan, T. G. Org. Lett. (2009), 11, 3734-3737. 
21. "Synthesis of Alkynyl Ethers and Low Temperature Sigmatropic Rearrangement of Ally and Benzyl Alkynyl Ethers" Sosa, J. R.; Tudjarian, A. T.; Minehan, T. G. Org. Lett. (2008), 10, 5091-5094. 
22. "Palladium-Catalyzed Reactions of Arylindium Reagents Prepared directly from Aryl Iodides and Indium Metal" Papoian, V.; Minehan, T. G. J. Org. Chem. (2008), 73, 7376-7379. 
23. "An Environmentally Benign Synthesis of cis-2,6-Disubstituted Tetrahydropyrans via Indium-Mediated Tandem Allylation / Prins Cyclization Reaction" Pham, M.; Allatabakhsh, A.; Minehan, T. G. J. Org. Chem. (2008), 73, 741-744. 
24. "Synthesis of Oxa-Bridged 7- and 8-Membered Rings Via Indium-Mediated Annulation of 1,4- and 1,5-Dicarbonyl Compounds with 3-Iodo-2-[(trimethylsilyl)methyl]propene" Allatabakhsh, A.; Pham, M.; Minehan, T. G. Heterocycles (2007), 72, 115-122. 
25. "Palladium-Catalyzed Reactions of Acetoxyenynes with Triorganoindium Reagents" Metza, J. T.; Terzian, R. A.; Minehan, T. G. Tetrahedron, (2006), 47, 8905-8910. 
26. “Low-Temperature n-Butyllithium-Induced Rearrangement of Allyl 1,1-Dichlorovinyl Ethers,” Christopher, A., Brandes, D., Kelly, S., Minehan, T. G. Org. Lett., (2006), 8, 451-454.

MS THESES

• Armen Nazarian, "Synthesis of azinomycin B-nogalamycin hybrid congener" (2019)
• Christine Dimirjian, "Towards the Synthesis of Diandraflavone" (2015)
• Xiao Cai, “Total synthesis of Polycarcin V” (2014)
• Miran Mavlan, “Synthesis of 3,3’-di-O-methylardimerin and evaluation of its DNA binding profile” (2014)
• Chikako Omura, “Synthesis of aryl piperidine and aryl aza-sugar compound: Mimics of DNA-intercalating agents” (2012)
• Samuel Rodriguez-Torres, “Development of a new route for the synthesis of 2-deoxy-C-aryl glycosides" (2010)