This program will continue to develop practical, flexible strategies for the enantioselective synthesis of six to nine membered ring ethers and apply the new strategies to the total synthesis of structurally novel and biologically important natural products. During the course of this investigation, new synthetic technologies will be explored for the asymmetric construction of cyclic ethers and carbocycles based on establishing acyclic stereochemical arrays followed by ring closure. During the next grant period the total synthesis of brevetoxin A will be completed. The synthesis of sorangicin A, brevenal, hemibrevetoxin B, sclerophytin A, brianthein A, and verillin will also be pursued. Important analogs of these natural products will also be prepared. A novel 3- component assembly of 1, 1'-disubstituted ether linkages, a new asymmetric acetate aldol, and an anti-glycolate aldol will be further developed and exploited. The dianioic Claisen rearrangement will be further developed for construction of quaternary stereogenic centers and applied to brianthein A and verillin. The total synthesis of brevetoxin A, sorangicin A, brevenal sclerophytin A, brianthein A and verillin will be carried out. New enantioselective methods for the synthesis of cyclic ethers and carbocycles will be investigated.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM060567-12
Application #
8018987
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Lees, Robert G
Project Start
2000-02-01
Project End
2013-01-31
Budget Start
2011-02-01
Budget End
2013-01-31
Support Year
12
Fiscal Year
2011
Total Cost
$323,033
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Crimmins, Michael T; Knight, John D; Williams, Philip S et al. (2014) Stereoselective synthesis of quaternary carbons via the dianionic Ireland-Claisen rearrangement. Org Lett 16:2458-61
Crimmins, Michael T; Hughes, Colin O (2012) Total synthesis of the proposed structure of aldingenin B. Org Lett 14:2168-71
Crimmins, Michael T; Dechert, Anne-Marie R (2012) Enantioselective synthesis of the C1-C6 and C7-C23 fragments of the proposed structure of iriomoteolide 1a. Org Lett 14:2366-9
Crimmins, Michael T; Haley, Matthew W; O'Bryan, Elizabeth A (2011) Formal synthesis of (+)-sorangicin A. Org Lett 13:4712-5
Crimmins, Michael T; Stauffer, Christina S; Mans, Mark C (2011) Total syntheses of (+)-vigulariol and (-)-sclerophytin A. Org Lett 13:4890-3
Crimmins, Michael T; Mans, Mark C; Rodriguez, Abimael D (2010) Total synthesis of the proposed structure of briarellin J. Org Lett 12:5028-31
Crimmins, Michael T; Shamszad, Mariam; Mattson, Anita E (2010) A highly convergent approach toward (-)-brevenal. Org Lett 12:2614-7
Crimmins, Michael T; Martin, Timothy J; Martinot, Theodore A (2010) Synthesis of the bis-tetrahydropyran core of amphidinol 3. Org Lett 12:3890-3
Crimmins, Michael T; O'Bryan, Elizabeth A (2010) Enantioselective total synthesis of spirofungins A and B. Org Lett 12:4416-9
Crimmins, Michael T; Dechert, Anne-Marie R (2009) Enantioselective total synthesis of (-)-pironetin: iterative aldol reactions of thiazolidinethiones. Org Lett 11:1635-8

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