Odorant Design Based on the Carbon/Silicon Switch Strategy

  title={Odorant Design Based on the Carbon/Silicon Switch Strategy},
  author={Reinhold Tacke and Stefan Metz},
  journal={Chemistry \& Biodiversity},
Silicon chemistry has been demonstrated to be a novel source of chemical diversity in odorant design. The carbon/silicon switch strategy, i.e., sila‐replacement in known odorants, is one of the methods currently used for the development of silicon‐based odorants. Examples resulting from this strategy are sila‐coranol, sila‐dimetol, sila‐linalool, sila‐muguetalcohol, sila‐majantol, sila‐hydratropyl acetate, sila‐bourgeonal, sila‐lilial, disila‐versalide, and disila‐okoumal. 
26 Citations
Sila-rhubafuran and Derivatives: Synthesis and Olfactory Characterization of Novel Silicon-Containing Odorants
Sila-rhubafuran (1b), a silicon analogue of the grapefruit odorant rhubafuran (1a), was synthesized and isolated as a 1:1 mixture of two racemic diastereomers. In addition, the structurally related
Drug Design Based on the Carbon/Silicon Switch Strategy
Silicon chemistry has been demonstrated to be a novel source of chemical diversity in drug design. The carbon/silicon switch strategy, i.e., the strategic replacement of a carbon atom with a silicon
Synthesis and Olfactory Properties of Silicon‐Containing Analogs of Rosamusk, Romandolide, and Applelide: Insights into the Structural Parameters of Linear Alicyclic Musks
A series of silicon-containing derivatives of linear alicyclic musks comprising sila-Rosamusk (3b), sila-Romandolide (5b), sila-Applelide (11b), and the corresponding dehydro derivatives was
Six‐Membered Silacycle Odorants: Synthesis and Olfactory Characterization of Si Analogues of Artemone, β‐Dynascone, and Herbac
Si-Artemone (4a), Si-β-Dynascone (5a), and Si-Herbac 6a, which are Si analogues of the commercial fragrance ingredients Artemone (1), β-Dynascone (2), and Herbac (3), were synthesized expediently by
Photocatalyzed cycloaromatization of vinylsilanes with arylsulfonylazides
A practical Ir(III)-catalyzed cycloaromatization of ortho-alkynylaryl vinylsilanes with arylsulfonyl azides for delivering naphthyl-fused benzosiloles under visible-light photoredox conditions and the reaction mechanism involving α-silyl radical Smiles rearrangement is revealed.
Access to Silylated Pyrazole Derivatives by Palladium-Catalyzed C-H Activation of a TMS group.
The experimental conditions used, which are fully compatible with the pyrazole ring, suggest that this reaction evolves through a concerted metalation-deprotonation (CMD) mechanism.
Synthesis and Olfactory Characterization of Silicon‐Containing Derivatives of the Acyclic Lily‐of‐the‐Valley Odorant 5,7,7‐Trimethyl‐4‐methylideneoctanal
To gain more information about the structureodor correlation in the family of lily‐of‐the‐valley or ‘muguet’ odorants, C/Si analogs 1a/1b and derivatives 2–6 were evaluated for their olfactory properties.
Ruthenium-Catalyzed Site-Selective Intramolecular Silylation of Primary C-H Bonds for Synthesis of Sila-Heterocycles.
This method provides a general, synthetically efficient approach to novel classes of Si-containing five-membered [1,3]-sila-heterocycles, including oxasilolanes, azasillanes, disila- heteroatoms, and germasilolane.
Novel silicon-based patchouli odorants of the trialkyl(1-hydroxy-1-methylethyl)silane type: design, synthesis, and olfactory properties.
The silanes MeR (2)SiC(OH)Me(2) (12) and R(3) SiC( OH)Me (14) (R=cyclopropyl) were found to resemble natural patchouli oil most closely, with an even lower odor threshold than the natural lead structure (-)-patchoulol (1).


Silicon Analogues of the Musk Odorant Versalide
Twofold sila-substitution (C/Si exchange) of the musk odorant Versalide (1a) provides Disila-versalide (1b). The silicon compound 1b and its derivatives 2b (Et/Me exchange) and 3b (Et/H exchange)
Silylating Reagents: A Powerful Tool for the Construction of Isosteric Analogs of Highly Branched Odorants
We have discovered that α‐[dimethyl(thexyl)silyl]acetaldehyde (=[dimethyl(1,1,2‐trimethylpropyl)silyl]acetaldehyde; 31) has a strong, woody odor. Structural analysis has shown resemblance to known
Studies on silicon‐containing fragrance raw materials I. Syntheses and structure‐odor relationship of acetals of 4‐trimethylsilyl‐3‐cyclohexenone and 4‐trimethylsilylcyclohexanone and their carbon counterparts
In order to investigate the structure-odor relationship of odoriferous compounds and search for new aroma chemicals, seven acetals of 4-trimethylsilyl-3-cyclohexenone and their carbon counterparts
The Si-2,4,6-Trimethoxyphenyl Moiety as a Novel Protecting Group in Organosilicon Chemistry: Alternative Synthesis of rac-Sila-venlafaxine
The Si-2,4,6-trimethoxyphenyl (Si-2,4,6-TMOP) moiety is claimed to be an effective protecting group for synthetic organosilicon chemistry. To demonstrate its high synthetic potential, the
Sila-Riechstoffe und Riechstoffe-Isostere, 10. Mitt. Ein neuer Weg zu Sila-β-Jonon
Preparation of sila-β-ionone (14) was possible by a novel route with yields nearly 5 times higher than before1, with the formerly unknown 1,1,3-trimethyl-1-silacyclohexanone-2 (6) as a key substance.
Silicon switches of marketed drugs.
The application of organosilicon chemistry is a strategy to develop best in class drugs applied to targets that have been validated as tractable and drug-able. Silicon switches of known drugs have
Sila-linalool as a pheromone analogue: A study on C/Si bioisosterism
In these electroantennographic studies (GC/EAD), both enantiomers of 2a and 2b were equally well perceived, indicating distinct bioisosteric relationships between the C/Si analogues linalool and sila-linalool.
Development of a New Building Block for the Synthesis of Silicon-Based Drugs and Odorants: Alternative Synthesis of the Retinoid Agonist Disila-bexarotene
With 4,4,5,5-tetramethyl-2-(3,5,5,8,8-pentamethyl-5,8-disila-5,6,7,8-tetrahydro-2-naphthyl)-1,3,2-dioxaborolane (5) a new building block for the synthesis of biologically active