Abstract

The objective of this proposed work is to develop methods for the synthesis of novel 1-acyldihydropyridines and to study their utility as synthetic intermediates.
Specific aims i nclude: 1. To study the asymmetric synthesis of 1-acyl-2-alkyl=1,2- dihydropyridines and 2-alkyl-2,3-dihydro-4-pyridones. 2. To study approaches to the enantioselective total synthesis of streptazolin, cannabisativine and allopumiliotoxin. 3. To investigate a general approach to enantioselective synthesis of various Lycopodium alkaloids via chiral dihydropyridine intermediates. The proposed methodology will be useful for the synthesis of compounds having a broad range of biological properties, i.e. neuroleptic, antihypertensive, anti-inflammatory, anticancer, anti-AIDS, and anticonvulsant activities.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM034442-15
Application #
2900600
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1989-01-01
Project End
2000-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
15
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
North Carolina State University Raleigh
Department
Chemistry
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