Abstract

This proposal focuses on the application of pericyclic reactions in new methodology for the synthesis of several important classes of organic compounds. Part I describes the further development of a general regiocontrolled annulation route to highly substituted aromatic and heteroaromatic compounds. The application of this methodology to the total synthesis of biologically active natural products will be investigated; specific target compounds include the aegyptinone antibiotics, eight related diterpenoid quinones isolated from the important Chinese drug Dan Shen, the antibiotic phenalenone diterpenes salvilenone and atrovenetin, the antihypertensive diterpene barbatusol, the antineoplastic diterpene taxmairin B, and the mitomycin antitumor antibiotics. Part II of the proposal describes a general strategy for the synthesis of alkynylketenes, a class of ketene derivatives which are at present almost completely unknown. The application of the electrocyclization of certain conjugated alkynylketenes will be investigated as a method for the synthesis of aromatic compounds and as a means of generating certain novel aromatic diradical species.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM028273-12
Application #
3275569
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1980-07-01
Project End
1995-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
12
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
Massachusetts Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139

  Publications

Willumstad, Thomas P; Boudreau, Paul D; Danheiser, Rick L (2015) Synthesis of Highly Substituted Quinolines via a Tandem Ynamide Benzannulation/Iodocyclization Strategy. J Org Chem 80:11794-805
Lam, Tin Yiu; Wang, Yu-Pu; Danheiser, Rick L (2013) Benzannulation via the reaction of ynamides and vinylketenes. application to the synthesis of highly substituted indoles. J Org Chem 78:9396-414
Willumstad, Thomas P; Haze, Olesya; Mak, Xiao Yin et al. (2013) Batch and flow photochemical benzannulations based on the reaction of ynamides and diazo ketones. Application to the synthesis of polycyclic aromatic and heteroaromatic compounds. J Org Chem 78:11450-69
Lan, Yu; Danheiser, Rick L; Houk, K N (2012) Why nature eschews the concerted [2 + 2 + 2] cycloaddition of a nonconjugated cyanodiyne. Computational study of a pyridine synthesis involving an ene-Diels-Alder-bimolecular hydrogen-transfer mechanism. J Org Chem 77:1533-8
Wang, Yu-Pu; Danheiser, Rick L (2011) Synthesis of 2-iodoynamides and regioselective [2+2] cycloadditions with ketene. Tetrahedron Lett 52:2111-2114
Benda, Konstantin; Knoth, Tanja; Danheiser, Rick L et al. (2011) A New Route to Silyl-substituted Cyclobutenones and Silylketenes. Tetrahedron Lett 52:46-48
Robinson, Julia M; Tlais, Sami F; Fong, Jennie et al. (2011) A [4 + 4] annulation strategy for the synthesis of eight-membered carbocycles based on intramolecular cycloadditions of conjugated enynes. Tetrahedron 67:9890-9898
Mak, Xiao Yin; Crombie, Aimee L; Danheiser, Rick L (2011) Synthesis of polycyclic benzofused nitrogen heterocycles via a tandem ynamide benzannulation/ring-closing metathesis strategy. Application in a formal total synthesis of (+)-FR900482. J Org Chem 76:1852-73
Sakai, Takeo; Danheiser, Rick L (2010) Cyano Diels-Alder and cyano ene reactions. Applications in a formal [2 + 2 + 2] cycloaddition strategy for the synthesis of pyridines. J Am Chem Soc 132:13203-5
Robinson, Julia M; Sakai, Takeo; Okano, Katsuhiko et al. (2010) Formal [2 + 2 + 2] cycloaddition strategy based on an intramolecular propargylic ene reaction/Diels-Alder cycloaddition cascade. J Am Chem Soc 132:11039-41

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