Efficient Macrocyclization by a Novel Oxy‐Oxonia‐Cope Reaction: Synthesis and Olfactory Properties of New Macrocyclic Musks

Zou, Yue; Mouhib, Halima; Stahl, Wolfgang; Goeke, Andreas; Wang, Quanrui; Kraft, Philip

doi:10.1002/chem.201200882

Cited by 28 publications

(9 citation statements)

References 44 publications

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“…For example, in addition to the aza-Claisen ring expansion method described earlier in Section 11.10, another sigmatropic process, a novel oxy-oxonia Cope rearrangement, has been employed in a route to a series of simple macrocyclic compounds potentially useful as musks. 332 Treatment of dialdehyde substrates 238 with boron trifluoride etherate prompted the rearrangement to form the 14-to 18-membered macrocyclic products 239 (n ¼ 8-12, Scheme 11.31), favouring the (Z)-stereoisomer by a ratio of 4 : 1 to 99 : 1. Smaller ring sizes failed to provide the desired macrocycle, as did alternative Lewis acids, while addition by syringe pump to maintain high dilution was necessary to minimize dimer formation.…”

Section: Miscellaneous Methodsmentioning

confidence: 99%

The Synthesis of Macrocycles for Drug Discovery

Peterson¹

2014

Macrocycles in Drug Discovery

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Despite the attractive nature of macrocyclic compounds for use in new pharmaceutical discovery, applications have been hindered due to the lack of appropriate synthetic methods, in particular for the construction of libraries of such molecules. However, over the last decade, a number of effective and versatile methodologies suitable for macrocyclic scaffolds have been developed and applied successfully. These include classical coupling and substitution reactions, ring-closing metathesis (RCM), cycloaddition (“click”) chemistry, multicomponent reactions (MCR), numerous organometallic-mediated processes and others. This chapter presents a comprehensive compilation of these strategies and provides examples of their use in drug discovery, along with a description of those approaches that have proven effective for the assembly of macrocyclic libraries suitable for screening.

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Section: Miscellaneous Methodsmentioning

confidence: 99%

The Synthesis of Macrocycles for Drug Discovery

Peterson¹

2014

Macrocycles in Drug Discovery

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“…Natural Product Communications Vol. 12 (6) 2017 989 oxy-oxonia-Cope reaction, which led to dl-muscone (1) [43]. Similarly, 14-to 18-membered macrocyclic compounds have been synthesized in 35 to 91% yield, in which relationship between conformational freedom and olfactory properties were evaluated (Scheme 30).…”

Section: Syntheses Of Muscone Muscopyridine and Civetonementioning

confidence: 99%

Diversity in the Syntheses of Muscone, Muscopyridine and Civetone

Hagiwara

2017

Natural Product Communications

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“…There are major recent advances on neurobiology, biophysics, biochemical fields [4][5][6][7], though it is still unclear how humans recognize odor. At this scenario, quantitative structure-activity relationship models (QSAR models) are valuable for the proposal of new potential musky smelling molecules [8][9][10][11][12]. Such approach allows for the reduction in the number of costly and unnecessary chemical syntheses.…”

Section: Theories Regarding Odor Prediction and Recognitionmentioning

confidence: 99%

Quantum Calculation for Musk Molecules Infrared Spectra towards the Understanding of Odor

Maia

Magalhães

Lerner

et al. 2014

Advances in Chemistry

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It is not clear so far how humans can recognize odor. One of the theories regarding structure-odor relationship is vibrational theory, which claims that odors can be recognized by their modes of vibration. In this sense, this paper brings a novel comparison made between musky and nonmusky molecules, as to check the existence of correlation between their modes on the infrared spectra and odor. For this purpose, sixteen musky odorants were chosen, as well as seven other molecules that are structurally similar to them, but with no musk odor. All of them were submitted to solid theoretical methodology (using molecular mechanics/molecular dynamics and Neglect of Diatomic Differential Overlap Austin Model 1 methods to optimize geometries) as to achieve density functional theory spectra information, with both Gradient Corrected Functional Perdew-Wang generalizedgradient approximation (GGA/PW91) and hybrid Becke, three-parameter, Lee-Yang-Parr (B3LYP) functional. For a proper analysis over spectral data, a mathematical method was designed, generating weighted averages for theoretical frequencies and computing deviations from these averages. It was then devised that musky odorants satisfied demands of the vibrational theory, while nonmusk compounds belonging either to nitro group or to acyclic group failed to fulfill the same criteria.

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Efficient Macrocyclization by a Novel Oxy‐Oxonia‐Cope Reaction: Synthesis and Olfactory Properties of New Macrocyclic Musks

Cited by 28 publications

References 44 publications

The Synthesis of Macrocycles for Drug Discovery

The Synthesis of Macrocycles for Drug Discovery

Diversity in the Syntheses of Muscone, Muscopyridine and Civetone

Quantum Calculation for Musk Molecules Infrared Spectra towards the Understanding of Odor

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