593-38-4Relevant academic research and scientific papers
AUTOMATED SYNTHESIS OF SMALL MOLECULES USING CHIRAL, NON-RACEMIC BORONATES
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, (2012/11/13)
Provided are methods for making and using chiral, non-racemic protected organoboronic acids, including pinene-derived iminodiacetic acid (PIDA) boronates, to direct and enable stereoselective synthesis of organic molecules. Also provided are methods for purifying PIDA boronates from solution. Also provided are methods for deprotection of boronic acids from their PIDA ligands. The purification and deprotection methods may be used in conjunction with methods for coupling or otherwise reacting boronic acids. Iterative cycles of deprotection, coupling, and purification can be performed to synthesize chiral, non-racemic compounds. The methods are suitable for use in an automated chemical synthesis process. Also provided is an automated small molecule synthesizer apparatus for performing automated stereoselective synthesis of chiral, non-racemic small molecules using iterative cycles of deprotection, coupling, and purification.
Synthesis of conjugated polyenes via sequential condensation of sulfonylphosphonates and aldehydes
Cichowicz, Nathan R.,Nagorny, Pavel
supporting information; experimental part, p. 1058 - 1061 (2012/04/05)
Selective metalation of sulfonylphosphonates results in sufficiently stable carbanions that undergo chemoselective Julia-Kocienski condensation with various aldehydes to provide (E)-allylic phosphonates in good yields and selectivities. The subsequent Horner-Wadsworth-Emmons condensation with aldehydes is used to synthesize various unsymmetrical trans-dienes, trienes, and tetraenes. This methodology is utilized for the concise synthesis of a naturally occurring fluorescent probe for membrane properties, β-parinaric acid.
APPARATUS AND METHODS FOR THE AUTOMATED SYNTHESIS OF SMALL MOLECULES
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Page/Page column 57-61, (2012/02/05)
Provided are methods for purifying N-methyliminodiacetic acid (MID A) boronates from solution. Also provided are methods for deprotection of boronic acids from their MIDA ligands. The purification and deprotection methods can be used in conjunction with methods for coupling or otherwise reacting boronic acids. Iterative cycles of deprotection, coupling, and purification can be performed to synthesize chemical compounds of interest. The methods are suitable for use in an automated chemical synthesis process. Also provided is an automated small molecule synthesizer apparatus for performing automated synthesis of small molecules using iterative cycles of deprotection, coupling, and purification in accordance with methods of the invention. Coupling and other reactions embraced by the invention include, without limitation, Suzuki-Miyaura coupling, oxidation, Swern oxidation, "Jones reagents" oxidation, reduction, Evans' aldol reaction, HWE olefmation, Takai olefmation, alcohol silylation, desilylation, /?-methoxybenzylation, iodination, Negishi cross-coupling, Heck coupling, Miyaura borylation, Stille coupling, and Sonogashira coupling.
SYSTEM FOR CONTROLLING THE REACTIVITY OF BORONIC ACIDS
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Page/Page column 22, (2009/02/11)
A protected organoboronic acid includes a boron having an sp3 hybridization, a conformationally rigid protecting group bonded to the boron, and an organic group bonded to the boron through a boron-carbon bond. A method of performing a chemical reaction includes contacting a protected organoboronic acid with a reagent, the protected organoboronic acid including a boron having an sp3 hybridization, a conformationally rigid protecting group bonded to the boron, and an organic group bonded to the boron through a boron-carbon bond. The organic group is chemically transformed, and the boron is not chemically transformed.
Simple, efficient, and modular syntheses of polyene natural products via iterative cross-coupling
Suk, Joong Lee,Gray, Kaitlyn C.,Paek, James S.,Burke, Martin D.
, p. 466 - 468 (2008/10/09)
This communication describes the discovery of air-stable and highly versatile B-protected haloalkenylboronic acid building blocks for iterative cross-coupling. These reagents enable the total synthesis of polyene natural products with extraordinary levels of simplicity, efficiency, and modularity. Specifically, all-trans-retinal, β-parinaric acid, and one-half of the amphotericin B macrolide skeleton were prepared using only the Suzuki-Miyaura reaction in an iterative manner to bring together collections of simple and readily accessible building blocks. In contrast to their boronic acid counterparts, the intermediate polyenylboronate esters are remarkably stable (to both column purification and storage), which is critical to their successful utilization. Moreover, the reactive boronic acids can be cleanly liberated using very mild aqueous base. These advances have enabled preparation of the longest polyene ever synthesized using the SM reaction. We additionally report, to the best of our knowledge, the first triply metal selective (Zn vs Sn and B) cross-coupling reaction, the first selective cross-coupling with a differentially ligated diboron reagent, and the first cross-couplings between polyenylchlorides and vinylboronic acids. Collectively, these new building blocks and methods can dramatically improve the way polyene natural products and their derivatives are synthesized in the laboratory. Copyright
Synthesis of polyconjugated fatty acids
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Page 16-17, (2010/02/10)
The present invention relates to fatty acids. In particular, the present invention provides polyconjugated fatty acids, and methods of their synthesis and their use.
Synthesis of four isomers of parinaric acid
Kuklev, Dmitry V.,Smith, William L.
, p. 215 - 222 (2007/10/03)
A simple and reliable method for synthesizing four isomers of parinaric acid from α-linolenic acid (ALA) in high yields is described. The methylene-interrupted, cis triene system (1,4,7-octatriene) of ALA and common to other naturally occurring polyunsaturated fatty acids was transformed to a conjugated tetraene system (1,3,5,7-octatetraene). The synthesis involves bromination of ALA using 0.l M Br2 in a saturated solution of NaBr in methanol, esterification of the fatty acid dibromides, double dehydrobromination by 1,8-diazabicyclo[5.4.0]undec-7-ene and saponification of the conjugated esters to a mixture of free conjugated acids. Addition of one molecule of bromine to the 12,13-double bond of ALA and subsequent dehydrobromination produces α-parinaric acid (9Z,11E,13E,15Z- octadecatetraenoic acid); addition of Br2 to the 9,10-double bond or 15,16-double bond and then dehydrobromination and rearrangement yields 9E,11E,13E,15Z-octadecatetraenoic or 9E,11E,13E,15Z-octadecatetraenoic acids, respectively. The mixture of parinaric acid isomers is obtained in 65% yield, and the isomers can be purified by preparative HPLC; alternatively, the isomers can be converted by base catalyzed cis-trans isomerization (or by treatment with I2) to exclusively β-parinaric acid (9E,11E,13E,15E- octadecatetraenoic acid). The various parinaric acid isomers were characterized by 1H NMR, 13C NMR, UV, GLC, HPLC and mass spectrometry.
A NEW, GENERAL, AND STEREOSELECTIVE SYNTHESIS OF LONG CHAIN TETRAENOIC ACIDS EXAMPLIFIED BY β-PARINARIC ACID
Hayashi, Toshio,Oishi, Takeshi
, p. 413 - 416 (2007/10/02)
All trans-9,11,13,15-octadecatetraenoic acid was first synthesized in a stereoselective manner, using pentadienyl and allyl dithiocarbamates as the starting materials.This synthesis confirmed that β-parinaric acid has all trans configurations about the four double bonds.
A 300 MHz 1H n.m.r. study of the Conjugated Tetraenes α and β-Parinaric Acid.
Smith, Roger M.,Croft, Kevin D.
, p. 477 - 490 (2007/10/02)
Analysis of the 300 MHz 1H n.m.r. spectra of α- and β-parinaric acids confirms their structures as (9Z,11E,13E,15Z)- and (9E,11E,13E,15E)-octadeca-9,11,13,15-tetraenoic acid, respectively, and permits the assignment of the coupling constants.
