- Observations on the Influence of Precursor Conformations on Macrocyclization Reactions
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Macrocycles hold great promise in drug discovery as an underutilized class of lead compounds. The low abundance of these molecules can, in part, be explained by the inherent difficulties in the synthesis of macrocycles and the lack of general methods for their rapid assembly. We have undertaken a research program aimed at developing methods for facile synthesis of macrocycles from simple precursors. The synthesis of two new cyclization precursors is described and the results of their reaction with thionyl chloride are presented and discussed. Whereas one acyclic diol smoothly underwent macrocyclization to afford a mixture of diastereomeric sulfites, subjection of the other precursor to identical reaction conditions resulted in the isolation of the linear dichloride. We hypothesize that there is a difference in the ability of the two molecules to adopt a conformation that is germane to macrocyclization, a proposition that is supported by conformational analyses using molecular mechanics. Macrocycles hold great promise in drug discovery; however, their synthetic generation through macrocyclization is nontrivial. Here, the synthesis of two new cyclization precursors is described and the results of the ensuing cyclization is reported and evaluated. Molecular modeling is used to explain the observed results and provide guidance for further work in this field.
- Hammersh?j, Peter,Beldring, Klavs,Nielsen, Anders R.,Fristrup, Peter,Clausen, Mads H.
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supporting information
p. 1533 - 1540
(2016/04/05)
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- Total synthesis of two γ-butyrolactone containing compounds (Z,11S)-3,4-trans-11-hydroxy-3-methyldodec-cis-6-en-4-olide and (Z)-3,4-trans-11-oxo-3-methyldodec-cis-6-en-4-olide
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The first total synthesis of (Z,11S)-3,4-trans-11-hydroxy-3-methyldodec-cis-6-en-4-olide and (Z)-3,4-trans-11-oxo-3-methyldodec-cis-6-en-4-olide was accomplished using Jacobsen hydrolytic kinetic resolution, Ohira-Bestmann reaction, regioselective alkyne
- Nomula, Rajesh,Raju, Galla,Radha Krishna, Palakodety
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p. 5976 - 5978
(2014/12/12)
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- A simple method for the conversion of primary alcohols into terminal olefins
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Treatment of benzyl ethers of primary alcohols with n-butyllithium (n-BuLi) afforded terminal olefins in good yield.
- Matsushita, Masayuki,Nagaoka, Yoko,Hioki, Hideaki,Fukuyama, Yoshiyasu,Kodama, Mitsuaki
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p. 1039 - 1040
(2007/10/03)
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