Abstract

The objective of this proposal is to develop methods for the synthesis of novel 1-acyldihydropyridines and to study their utility as synthetic intermediates.
Specific aims are (1) To study the asymmetric synthesis of 1-acyl-2-alkyl-1,2-dihydropyridines and 2-alkyl-2, 3-dihydro- 4 - pyridones. (2) To investigate the asymmetric synthesis and synthetic utility of 1-acyl-2-triphenylsilyl-2,3-dihydro-4-pyridones. (3) To develop enantioselective syntheses of various indolizidine and quinolizidine alkaloids using homochiral 2,3-dihydro-4-pyridones as synthetic intermediates. The proposed methodology will be useful for tbe synthesis of compounds having a broad range of biological properties, i.e. neuroleptic, antihypertensive, antiinflamatory, antitumor, and anticonvulsant activities.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM034442-10
Application #
3285445
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1989-01-01
Project End
1995-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
10
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
North Carolina State University Raleigh
Department
Type
Schools of Arts and Sciences
DUNS #
City
Raleigh
State
NC
Country
United States
Zip Code
27695

  Publications

Tsukanov, Sergey V; Comins, Daniel L (2014) Total synthesis of alkaloid 205B. J Org Chem 79:9074-85
Cash, Brandon M; Prevost, Natacha; Wagner, Florence F et al. (2014) Studies toward the total synthesis of dihydrolycolucine. Preparation of AB and CEF ring fragments. J Org Chem 79:5740-5
Sahn, James J; Comins, Daniel L (2010) [2 + 2] Photochemical cycloaddition/ring opening of 6-alkenyl-2,3-dihydro-4-pyridones. J Org Chem 75:6728-31
Wolfe, Bradley H; Libby, Adam H; Al-Awar, Rima S et al. (2010) Asymmetric synthesis of all the known phlegmarine alkaloids. J Org Chem 75:8564-70
McCall, W Stephen; Comins, Daniel L (2009) Synthesis of 1,3-amino alcohol derivatives via a silicon-mediated ring-opening of substituted piperidines. Org Lett 11:2940-2
McCall, W Stephen; Grillo, Teresa Abad; Comins, Daniel L (2008) N-acyldihydropyridones as synthetic intermediates. A stereoselective synthesis of acyclic amino alcohols containing multiple chiral centers. J Org Chem 73:9744-51
McCall, W Stephen; Grillo, Teresa Abad; Comins, Daniel L (2008) Stereoselective synthesis of acyclic amino alcohols via von Braun ring opening of chiral piperidines. Org Lett 10:3255-7
Bharathi, Pandi; Comins, Daniel L (2008) Asymmetric synthesis of C2-symmetric vicinal diamines via reductive dimerization of N-acylpyridinium and related salts. Org Lett 10:221-3
Comins, Daniel L; Dinsmore, Jason M; Marks, Lucas R (2007) One-pot terminal alkene homologation using a tandem olefin cross-metathesis/allylic carbonate reduction sequence. Chem Commun (Camb) :4170-1
Gotchev, Dimitar B; Comins, Daniel L (2006) Synthetic studies toward (-)-FR901483 using a conjugate allylation to install the C-1 quaternary carbon. J Org Chem 71:9393-402

Showing the most recent 10 out of 29 publications