(provided by 8applicant):
The specific aims of this program are to develop a practical, flexible strategy 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 medium ring ethers via olefin metathesis and tandem ring closing olefin metathesis reactions. Convenient access to alpha, alpha'-disubstituted ether linkages with control of the absolute stereochemistry at the positions alpha to the ether linkage is critical to the overall success of this program. Two important new approaches have already evolved from this program: 1) a syn or anti selective aldol reaction of chlorotitanium enolates of glycolyl oxazolidinethiones and 2) a highly versatile asymmetric glycolate alkylation reaction for the construction of alpha, alpha'-disubstituted ethers. Completion of the syntheses of brevetoxin A, gigantecin and mucocin are anticipated during the next grant period. Further development of the general approach to medium ring ethers will focus on the development of an intramolecular Diels-Alder approach to the eunicellin and cladiellin class of diterpenes including the cytotoxic agents astrogorgin and 4-Deoxyasbestinin A. A new strategy for the rapid construction of cis-2,6-distubstituted tetrahydropyrans that establishes both the C2 and the C6 stereogenic centers in a single step will also be investigated and applied to the total synthesis of the cytotoxin lasonolide A.
| 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; Ellis, J Michael; Emmitte, Kyle A et al. (2009) Enantioselective total synthesis of brevetoxin A: unified strategy for the B, E, G, and J subunits. Chemistry 15:9223-34 |
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