Dr. N. D. Prasad Atmuri
N. D. Prasad Atmuri was born in India, in 1984. After receiving his M.Sc. degree in Organic Chemistry from Nagarjuna University in 2006, he worked 2 years for Hetero drugs Ltd. as R & D Chemist and 4.6 years as an Associate Scientist for Syngene International Ltd, India. In 2013, he began graduate studies at the Université de Montréal under the direction of Professor William D. Lubell.
His research was highly focused on synthesis of novel Azabicyclo[X.Y.Z]alkanones amino acid derivatives via Transannular cyclization of unsaturated lactams. Constrained dipeptide lactam and azabicyclo[X.Y.0]alkanone rings have shown great utility for the mimicry of biologically active peptide secondary structures. Many synthetic strategies were available to make these different ring sizes. However, they often require long reaction sequences and each system has its own synthetic strategy. Our goal involves to make all ring systems in a common approach. Electrophilic transannular cyclization of 8-, 9-, and 10- membered macrocyclic dipeptide lactams has given successful entry to iodo substituted 5,5-, 5,6, 6,5-, 6,4-, 6,6-, and 7,5-fused ring systems. This strategy involves coupling of 4−7-carbon chain length ω-olefin amino carboxylates in different combinations of N- and C- terminals, followed by RCM. Interestingly, we developed transition metal catalyzed cross coupling reactions to make different chain length of ω-olefin amino with iodoalanine as a common starting material. Some of the lactams were resistant to transannular iodoamidation with simple iodine. A breakthrough in the transannular iodolactamization occurred on addition of hypervalent (III) Iodine to the Iodine mixture, which converts to iodo-bicycles diastereoselectively. Moreover, after Transannular cyclization, iodine is used as handle for sidechain functionality . Another goal of his Ph.D. research was to develop further libraries of these substituted bicycles to study biological activities and probe structure-activity relationships for different therapeutics.
M.Sc. Thesis Title: “Azabicycloalkanone synthesis by Transannular Cyclization.” (PDF)
Ph.D. Thesis Title: “Design, Synthesis and Biological Applications of Azabicycloalkanone Amino Acid
Atmuri, N. D. P.; Lubell, W. D. “Stereo- and regiochemical transannular cyclization of a common hexahydro-1H-azonine to afford three different indolizidinone dipeptide mimetics.” J. Org. Chem. 2020, 85, 1340−1351 https://pubs.acs.org/doi/10.1021/acs.joc.9b01861
Fatemeh M. M.*, Atmuri, N. D. P.*, Bourguet, C. B., Jennifer R. F., Hou X., Chemtob. S, Lubell W. D. “Paired Utility of Aza-Amino Acyl Proline and Indolizidinone Amino Acid Residues for Peptide Mimicry: Conception of Prostaglandin F2a Receptor Allosteric Modulators that Delay Preterm Birth.” J. Med. Chem. 2019, 62, 4500–4525. (*equal) https://pubs.acs.org/doi/pdf/10.1021/acs.jmedchem.9b00056
Mulamreddy R.; Atmuri, N. D. P.; Lubell, W. D. “ 4-Vinylproline. ” J. Org. Chem. 2018, 83, 13580–13586. https://pubs.acs.org/doi/abs/10.1021/acs.joc.8b02177
Atmuri, N. D. P.; Reilley, D. J.; Lubell, W. D. “Peptidomimetic Synthesis by Way of Diastereoselective Iodoacetoxylation and Transannular Amidation of 7–9-Membered Lactams.” Org. Lett. 2017, 19, 5066–5069. https://pubs.acs.org/doi/abs/10.1021/acs.orglett.7b02275
Atmuri, N. D. P.; Lubell, W. D. “Insight into Transannular Cyclization Reactions To Synthesize Azabicyclo [X.Y.Z] alkanone Amino Acid Derivatives from 8-, 9-, and 10- Membered Macrocyclic Dipeptide Lactams.” J. Org. Chem. 2015, 80, 4904–4918. https://pubs.acs.org/doi/abs/10.1021/acs.joc.5b00237
Atmuri, N. D. P.; Lubell, W. D. “Preparation of N-(Boc)-Allylglycine Methyl Ester Using a Zinc-Mediated, Palladium-Catalyzed Cross-Coupling Reaction.” Org. Synth. 2015, 92, 103–116. http://www.orgsyn.org/Content/pdfs/procedures/v92p0103.pdf
J. Org. Chem. 2020, 85, 1340−1351, Abstract was selected for a cover page of JOC Special Issue, “Modern Peptide and Protein Chemistry” https://pubs.acs.org/toc/joceah/85/3