Convenient Syntheses and Biological Activity of Novel ω-trans-(Bicyclopropyl)- and ω-(Bicyclopropylidenyl)-Substituted Fatty Acids and Their Derivatives

Löhr, Sandra; Jacobi, Carsten; Johann, André; Gottschalk, Gerhard; Meijere, Armin de

doi:10.1002/1099-0690(200009)2000:17<2979::aid-ejoc2979>3.0.co;2-a

Cited by 15 publications

(12 citation statements)

References 22 publications

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“…[55b,57] ) the THP-protected (bicyclopropylidenyl)alkanols 7rϪw were reduced to the trans-bicyclopropyl derivatives 167rϪw (Scheme 32) which, after deprotection, were oxidized to bicyclopropyl-substituted fatty acids. The latter were investigated for their biological activity and degradation [9] or applied to prepare liquid crystalline compounds with bicyclopropyl-substituted side chains. [58] Scheme 32. trans-Stereoselective reduction of the double bonds in the THP-protected (bicyclopropylidenyl)alkanols 7rϪw (see ref.…”

Section: Miscellaneousmentioning

confidence: 99%

An Evolving Multifunctional Molecular Building Block: Bicyclopropylidene

2000

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The elucidation of the chemistry of the highly strained and unusually tetrasubstituted alkene bicyclopropylidene (2), has proved to be fruitful, both with respect to synthetic applications as a multifunctional C 6 building block and for the understanding of certain reaction principles. The different, and steadily improved, methods developed over the last thirty years for the preparation of this unusual alkene, and the more recent methods for the synthesis of functionally substituted as well as spirocyclopropanated derivatives, are presented. The rich chemistry of bicyclopropylidene, beginning with its well-known thermal rearrangement and dimeriz-[a] and books. His scientific achievements have been published in over 420 original publications, review articles, and chapters in books. His current research interests include the development of new cascade reactions for the efficient construction of complex skeletons and new small-ring building blocks to be applied in the synthesis of natural and nonnatural compounds, new highly strained polycyclic compounds with interesting properties, as well as the development of new synthetic methodology based on metal-mediated and -catalyzed transformations of organic compounds.

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Section: Miscellaneousmentioning

confidence: 99%

An Evolving Multifunctional Molecular Building Block: Bicyclopropylidene

2000

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“…Bicyclopropylidene (1), a readily available C 6 -building block containing two cyclopropane rings, 7 has been shown to be easily transformed to a variety of functionally monosubstituted derivatives by deprotonation with n-butyllithium in THF at 0°C followed by electrophilic substitution with appropriate reagents. 8,9 Thus, reaction of lithiobicyclopropylidene with appropriate trialkylboronates should lead to bicyclopropylidenylboronates, and indeed, treatment of lithiated bicyclopropylidene with 2-isopropyloxy-4,4,5,5-tetramethyl-1,3-dioxa-2-borolane gave the air-stable borolane 2 in 76% yield after chromatographic purification on silica gel. 11 failed.…”

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confidence: 99%

2-(Bicyclopropylidenyl)- and 2-(trans-2′-Cyclopropylcyclopropyl)-4,4,5,5-tetramethyl-1,3-dioxa-2-borolane and Their Palladium-Catalyzed Cross-Coupling Reactions

Löhr

Meijere

2001

Synlett

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The bicyclopropylidenylboronate 2 was prepared in 76% yield from lithiated bicyclopropylidene (1) and 2-isopropyloxy-4,4,5,5-tetramethyl-1,3-dioxa-2-borolane. Birch reduction of 2 furnished 2-(trans-2'-cyclopropylcyclopropyl)-4,4,5,5-tetramethyl-1,3-dioxa-2-borolane (3) in 79% yield. Under palladium catalysis, the latter was successfully coupled with a variety of aryl and alkenyl halides to give the corresponding (2'-cyclopropylcyclopropyl)-substituted arene 6 (52-75% yield) and alkene derivatives 11a,b (48-59%), respectively. Twofold and even threefold couplings of 2 with 1,2-dibromo-and 1,3,5-tribromobenzene were also successful. trans-3-(2'-Cyclopropylcyclopropyl)acrylic acid 12 could easily be obtained from 11a in 74% yield.The palladium-catalyzed cross coupling between various organylboronates and an alkenyl or an aryl halide (Suzuki coupling) has emerged as a powerful general method for C-C-bond formation. 1 Being largely unaffected by the presence of water, and compatible with a broad range of functional groups, the Suzuki reaction has frequently been applied in the synthesis of natural products. 1,2 This cross coupling can favorably be carried out with cyclopropyl derivatives, as demonstrated by the successful coupling of cyclopropylboronates with aryl halides 3 and that of iodocyclopropanes with alkenyl, aryl and cyclopropylboronates, 4 including one case of a bicyclopropylboronate. 4b Some coupling reactions even work with aryl or alkenyl halides and cyclopropylboronic acids, which were obtained by cyclopropanating alkenylboronic acids. 5 The key step in all previously reported syntheses of bicyclopropyl derivatives was a cyclopropanation of a cyclopropylalkenyl derivative. 6 We want to report on a new simple diastereoselective synthesis of a trans-2-cyclopropylcyclopropylboronate and its palladium-catalyzed coupling with various aryl and alkenyl halides.Bicyclopropylidene (1), a readily available C 6 -building block containing two cyclopropane rings, 7 has been shown to be easily transformed to a variety of functionally monosubstituted derivatives by deprotonation with n-butyllithium in THF at 0°C followed by electrophilic substitution with appropriate reagents. 8,9 Thus, reaction of lithiobicyclopropylidene with appropriate trialkylboronates should lead to bicyclopropylidenylboronates, and indeed, treatment of lithiated bicyclopropylidene with 2-isopropyloxy-4,4,5,5-tetramethyl-1,3-dioxa-2-borolane gave the air-stable borolane 2 in 76% yield after chromatographic purification on silica gel. Scheme 1 A: 1) nBuLi, THF, -30°C; 2) 2-isopropyloxy-4,4,5,5-tetramethyl-1,3-dioxa-2-borolane, THF, -78®20°C, 24 h; 3) NH 4 Cl, H 2 O. -B: 1) Li, NH 3 (lq.), -78°C; 2) MeOH (3 equiv.); 3) 2 N HCl (3.5 equiv.). The trans-diastereoselective reduction of the double bond in the bicyclopropylidenylboronate 2 was easily accomplished under Birch conditions with lithium in liquid ammonia at -78°C, as reported for other bicyclopropylidene derivatives by de Meijere et al., 9 to give 2-(trans-2'-cyclopropylcyclopropyl)-4,4,...

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“…The alkyl chain elongation in allyl ITCs also increases their lipophilicity (log P value), suggesting that the inhibitory potency of inflammatory factors by ITCs may be related to their log P values. Furthermore, substitution of the methylsulfinyl group in 6-MSITC with a formyl (6-isothiocyanatohexanal [ 49 , 73 ]), a methylsulfanyl (1-isothiocyanato-6-(methylthio)hexane [ 49 , 74 ]), or a methyl ( n -hexyl ITC [ 49 ]), attenuated the inhibitory activity. Polar surface area (PSA) value of these analogues is lower than that of 6-MSITC.…”

Section: Structure-activity Relationshipmentioning

confidence: 99%

Molecular Mechanisms Underlying Anti-Inflammatory Actions of 6-(Methylsulfinyl)hexyl Isothiocyanate Derived from Wasabi (Wasabia japonica)

Uto

Hou

Morinaga

et al. 2012

Advances in Pharmacological Sciences

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6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a major bioactive compound in wasabi (Wasabia japonica), which is a typical Japanese pungent spice. Recently, in vivo and in vitro studies demonstrated that 6-MSITC has several biological properties, including anti-inflammatory, antimicrobial, antiplatelet, and anticancer effects. We previously reported that 6-MSITC strongly suppresses cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and cytokines, which are important factors that mediate inflammatory processes. Moreover, molecular analysis demonstrated that 6-MSITC blocks the expressions of these factors by suppressing multiple signal transduction pathways to attenuate the activation of transcriptional factors. Structure-activity relationships of 6-MSITC and its analogues containing an isothiocyanate group revealed that methylsulfinyl group and the length of alkyl chain of 6-MSITC might be related to high inhibitory potency. In this paper, we review the anti-inflammatory properties of 6-MSITC and discuss potential molecular mechanisms focusing on inflammatory responses by macrophages.

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Convenient Syntheses and Biological Activity of Novel ω-trans-(Bicyclopropyl)- and ω-(Bicyclopropylidenyl)-Substituted Fatty Acids and Their Derivatives

Cited by 15 publications

References 22 publications

An Evolving Multifunctional Molecular Building Block: Bicyclopropylidene

An Evolving Multifunctional Molecular Building Block: Bicyclopropylidene

2-(Bicyclopropylidenyl)- and 2-(trans-2′-Cyclopropylcyclopropyl)-4,4,5,5-tetramethyl-1,3-dioxa-2-borolane and Their Palladium-Catalyzed Cross-Coupling Reactions

Molecular Mechanisms Underlying Anti-Inflammatory Actions of 6-(Methylsulfinyl)hexyl Isothiocyanate Derived from Wasabi (Wasabia japonica)

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