The aims of this proposal are to discover new reactivity in addition reactions to carbonyl compounds, at times in the context of the total synthesis of natural products.
Specific aims i nclude completion of the synthesis of the oxo-polyene macrolide antibiotic RK-397. We have prepared a late stage intermediate and in the next funding period, we will complete this synthesis. We will also study an intramolecular vinylogous aldol reaction similar to the Yamamoto intermolecular vinylogous aldol and we will apply this method to the synthesis of the cytotoxic macrolide, arenolide. We will also study a new strategy for conducting intramolecular aldol reactions based on using C-silylated esters as the nucleophilic component. These compounds are compatible with aldehydes and should react only upon activation. We have also developed an interesting asymmetric O-nucleophilic catalyst for enantioselective acyl transfer in the past funding period. This catalyst currently displays s-values of up to 31 for the methanolysis of alpha-acetoxy N- acylthiazolidinethiones. We will explore this catalyst system in the upcoming funding period and delineate its scope and limitations.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Schwab, John M
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University of Colorado at Boulder
Schools of Arts and Sciences
United States
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Chando, Katelyn M; Bailey, Patricia A; Abramite, Joseph A et al. (2015) Regioselective Ring Opening of Di-isopropylsilylenes Derived from 1,3-Diols with Alkyl Lithium Reagents. Org Lett 17:5196-9
Gazaille, Jeffrey A; Abramite, Joseph A; Sammakia, Tarek (2012) Toward the synthesis of (+)-peloruside A via an intramolecular vinylogous aldol reaction. Org Lett 14:178-81
Gazaille, Jeffrey A; Sammakia, Tarek (2012) The vinylogous aldol reaction of unsaturated esters and enolizable aldehydes using the novel Lewis acid aluminum tris(2,6-di-2-naphthylphenoxide). Org Lett 14:2678-81
Zhang, Yingchao; Arpin, Carolynn C; Cullen, Aaron J et al. (2011) Total synthesis of dermostatin A. J Org Chem 76:7641-53
Hao, Xin; Nguyen, Tam; Kearns, Daniel B et al. (2011) New inhibitors of colony spreading in Bacillus subtilis and Bacillus anthracis. Bioorg Med Chem Lett 21:5583-8
Mai, Cheng-Kang; Sammons, Matthew F; Sammakia, Tarek (2010) A concise formal synthesis of diazonamide A by the stereoselective construction of the C10 quaternary center. Angew Chem Int Ed Engl 49:2397-400
Mai, Cheng-Kang; Sammons, Matthew F; Sammakia, Tarek (2010) Alpha-arylation of 3-aryloxindoles. Org Lett 12:2306-9
Mitton-Fry, Mark J; Cullen, Aaron J; Sammakia, Tarek (2007) The total synthesis of the oxopolyene macrolide RK-397. Angew Chem Int Ed Engl 46:1066-70
Abramite, Joseph A; Sammakia, Tarek (2007) Application of the intramolecular Yamamoto vinylogous aldol reaction to the synthesis of macrolides. Org Lett 9:2103-6
Notte, Gregory T; Sammakia, Tarek (2006) Kinetic resolution of protected alpha-amino acid derivatives by a chiral O-nucleophilic acyl transfer catalyst. J Am Chem Soc 128:4230-1

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