More than a third of all current prescriptions have the decalin subunit embedded within the structure. The prevalence of biologically-potent decalins has spawned numerous syntheses though a pressing need still exists for rapid, asymmetric decalin syntheses. The focus of this proposal is to develop three complementary syntheses that rapidly synthesize highly substituted decalins. Key to achieving this aim is a multicomponent 1,2-1,4-addition alkylation reaction that allows for one of the few annulations with unsaturated nitriles. Harnessing this potential with bifunctional Grignard reagents, and particularly with allylsilanes, can conceptually provide access to a diverse array of nitrile containing decalins, hydrindanes, and octalins. The strategy is illustrated with the synthesis of potamogetonin as a potential AIDs inhibitor. Synthesizing potamogetonin not only illustrates the rapid construction of decalin-containing drugs but will determine whether more flexible terpenoids, labdanes in particular, are better AIDs inhibitors than their more rigid analogs. The four specific aims of this proposal are: * Domino addition-alkylations with bifunctional Grignards * Enantio- and diastereoselective addition-alkylations * Multicomponent addition-allylsilane cyclizations * Potamogetonin synthesis to probe the efficacy as an NNRTI Fulfilling these aims will advance knowledge of both nitrile-based reactions and NNRTI inhibitors.
| Alwedi, Embarek; Lujan-Montelongo, J Armando; Pitta, Bhaskar R et al. (2018) Asmic: An Exceptional Building Block for Isocyanide Alkylations. Org Lett 20:5910-5913 |
| Chepyshev, Sergiy V; Lujan-Montelongo, J Armando; Chao, Allen et al. (2017) Alkenyl Isocyanide Conjugate Additions: A Rapid Route to ?-Carbolines. Angew Chem Int Ed Engl 56:4310-4313 |
| Li, Yajun; Fleming, Fraser F (2016) Direct Conversion of Nitriles into Alkene ""Isonitriles"". Angew Chem Int Ed Engl 55:14770-14773 |
| Chao, Allen; Lujan-Montelongo, J Armando; Fleming, Fraser F (2016) Isocyano Enones: Addition-Cyclization Cascade to Oxazoles. Org Lett 18:3062-5 |
| Li, Yajun; Chao, Allen; Fleming, Fraser F (2016) Isonitrile alkylations: a rapid route to imidazo[1,5-a]pyridines. Chem Commun (Camb) 52:2111-3 |
| Lujan-Montelongo, J Armando; Estevez, Angel Ojeda; Fleming, Fraser F (2015) Alkyl Sulfinates: Formal Nucleophiles for Synthesizing TosMIC Analogs. European J Org Chem 2015:1602-1605 |
| Lu, Ping; Pakkala, Venkata S; Evanseck, Jeffrey D et al. (2015) Metalated nitriles: SNi' cyclizations with a propargylic electrophile. Tetrahedron Lett 56:3216-3219 |
| Chakrabarty, Suravi; Choudhary, Shruti; Doshi, Arpit et al. (2014) Catalytic Isonitrile Insertions and Condensations Initiated by RNC-X Complexation. Adv Synth Catal 356:2135-2196 |
| Lujan-Montelongo, Jesus A; Lu, Ping; Liu, Wang et al. (2013) Metalated nitriles: S(N)i and S(N)i' installation of contiguous quaternary-tertiary and quaternary-quaternary centers. Chemistry 19:8746-50 |
| Yao, Lihua; Pitta, Bhaskar; Ravikumar, P C et al. (2012) Transmissive olefination route to putative ""morinol I"" lignans. J Org Chem 77:3651-7 |
Showing the most recent 10 out of 21 publications
