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Ring Junction (ring + junction)
Selected AbstractsChronic Actinic Dermatitis to Sesquiterpene Lactones: [2+2] Photoreaction Toward Thymidine of (+) and (,) ,-Methylene-Hexahydrobenzofuranone with a cis Ring JunctionPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 3 2010Sébastien Fuchs (+) and (,) ,-methylene-hexahydrobenzofuranone derivatives with a stereochemically pure cis ring junction were used as models of sesquiterpene lactones to study their photoreactivity toward thymidine. After 313 nm irradiation of a deoxygenated acetone solution of lactone models and thymidine, six [2+2] photoadducts were isolated for each enantiomer and fully characterized by a combination of NMR experiments. A common syn regioselectivity and exo stereoselectivity were observed for photoadducts. This high photoreactivity of ,-methylene-,-butyrolactone ring toward thymidine could be an explanation of the progressive evolution of allergic contact dermatitis toward chronic actinic dermatitis. [source] Utilization of a Common Pathway for the Synthesis of High Affinity Macrocyclic Grb2 SH2 Domain-Binding Peptide Mimetics That Differ in the Configuration at One Ring JunctionCHEMISTRY & BIODIVERSITY, Issue 4 2005Zhen-Dan Shi As typified by 2-{(9S,10S,14R,18S)-18-(2-amino-2-oxoethyl)-14-[(5-methyl-1H -indol-1-yl)methyl]-8,17,20-trioxo-10-[4-(phosphonomethyl)phenyl]-7,16,19-triazaspiro[5.14]icos-11-en-9-yl}acetic acid ((14R)- 1b), ring-closing methathesis-derived macrocyclic tetrapeptide mimetics have recently been reported that bind with high affinity to Grb2 SH2 domains in both extracellular and whole-cell assays. The synthetic complexity of this class of agents limits further therapeutic development. Although a significant component of this synthetic complexity arises from the presence of three stereogenic centers, C(9) (S), C(10) (S), and C(14) (R), it is unclear whether stereoselective introduction of defined configuration at C(14) is required for high-affinity binding. Reported herein is a synthetic route to these macrocycles lacking stereoselectivity in the formation of the C(14) ring junction, which is four synthetic steps shorter than the original stereoselective synthesis. Separation of C(14)-epimers obtained by this approach was achieved by preparative HPLC. Molecular-dynamics studies of ligands bound to the Grb2 SH2 domain protein indicated that the (14R)-configuration should display more-favorable interactions with the protein relative to the (14S)-epimer. Indeed, although surface-plasmon-resonance-derived binding constants to Grb2 SH2 domain protein indicated that the affinity of the (14R)-epimer (KD=4.8,nM) is greater than that of the (14S)-epimer (KD=11,nM), it is only marginally so. Therefore, little affinity would be lost through a non-stereoselective synthesis of the C(14)-center. Further studies are in progress to explore reduced structural complexity at the C(14)-center. [source] The Intramolecular Aromatic Electrophilic Substitution of Aminocyclopropanes Prepared by the Kulinkovich,de Meijere Reaction,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 21 2005Laurent Larquetoux Abstract This article describes new examples of intramolecular Kulinkovich,de Meijere reactions applied to carboxylic amides bearing an olefin moiety and an aromatic ring at a suitable position. Upon heating, the aminocyclopropanes thus obtained undergo intramolecular aromatic electrophilic substitution to afford polycyclic systems. Among the various starting materials prepared, best results are obtained from indole and phenol derivatives. In each case, a benzylic quaternary centre is introduced at the newly-formed ring junction. On one example, the efficiency of the cyclisation has been dramatically improved using a catalytic amount of para -toluenesulfonic acid. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Chronic Actinic Dermatitis to Sesquiterpene Lactones: [2+2] Photoreaction Toward Thymidine of (+) and (,) ,-Methylene-Hexahydrobenzofuranone with a cis Ring JunctionPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 3 2010Sébastien Fuchs (+) and (,) ,-methylene-hexahydrobenzofuranone derivatives with a stereochemically pure cis ring junction were used as models of sesquiterpene lactones to study their photoreactivity toward thymidine. After 313 nm irradiation of a deoxygenated acetone solution of lactone models and thymidine, six [2+2] photoadducts were isolated for each enantiomer and fully characterized by a combination of NMR experiments. A common syn regioselectivity and exo stereoselectivity were observed for photoadducts. This high photoreactivity of ,-methylene-,-butyrolactone ring toward thymidine could be an explanation of the progressive evolution of allergic contact dermatitis toward chronic actinic dermatitis. [source] Dibothrioclinin I and II, epimers from Gerbera piloselloides (L.) CassACTA CRYSTALLOGRAPHICA SECTION C, Issue 10 2003Cheng Wang Dibothrioclinin I and II, namely (+)-(11R,12S,25R,27S)- and (±)-(11RS,12RS,25RS,27SR)-3,3,7,17,21-pentamethyl-4,12,18,26-tetraoxaheptacyclo[15.11.1.02,15.05,14.06,11.019,28.020,25]nonacosa-5(14),6,8,10,19(28),20,22,24-octaene-13,27-dione, respectively, are C30H28O6 epimers which are derived from two bothrioclinin moieties joined so as to create an additional six-membered ring. Structurally, the epimers differ only by inversion at one C atom of a central ring junction and the corresponding six-membered rings have similar conformations in each molecule, except for one ring adjacent to this inversion site. [source] [1a(1a,,5,,9a,)]-1,1a,4,5,7,8,9,9a-Octahydro-3-hydroxy-1,1,2,5-tetramethyl-7-methylene-6H -cyclopropa[3,4]cyclohept[1,2- e]inden-6-oneACTA CRYSTALLOGRAPHICA SECTION C, Issue 5 2000N. T. Do Valle Interest in the title structure, C20H24O2, lies in the novel cis ring junction between the three- and seven-membered rings. This stereochemical arrangement causes the methylene moiety and the cycloheptane ring to be twisted out of the plane of the aromatic ring. The cyclopropane ring is also twisted out of the plane of the aromatic system. The molecules are linked by an O,H,O hydrogen bond [O,O 2.741,(3),Å]. [source] Intramolecular Alkynylogous Mukaiyama Aldol Reaction Starting from Bicyclic Alkanones Tethered to Alkynyl Esters: Formal Total Synthesis of (±)-Hamigeran,BCHEMISTRY - A EUROPEAN JOURNAL, Issue 17 2009Laurence Miesch Dr. Abstract Selecting the ring: tert -Butyldimethylsilyltriflate (TBSOTf)/NEt3 treatment of alkynyl esters tethered to bicycloalkanones leads to the formation of tricyclic allenoates with total diasteroselectivity at the ring junction. An intramolecular alkynylogous Mukaiyama aldol reaction promoted by a TBSOTf/NEt3 dual activation is involved. This novel methodology was illustrated by a formal total synthesis of (±)-hamigeran,B. tert -Butyldimethylsilyltriflate (TBSOTf)/NEt3 treatment of alkynyl esters tethered to bicycloalkanones led to tricyclic allenoates with total diastereoselectivity for the ring junction. The allenoates result from an intramolecular alkynylogous Mukaiyama aldol reaction promoted by a TBSOTf/NEt3 dual activation, with key intermediates of silylalkynylketene acetals. This novel methodology was illustrated by a formal total synthesis of (±)-hamigeran,B. [source] Utilization of a Common Pathway for the Synthesis of High Affinity Macrocyclic Grb2 SH2 Domain-Binding Peptide Mimetics That Differ in the Configuration at One Ring JunctionCHEMISTRY & BIODIVERSITY, Issue 4 2005Zhen-Dan Shi As typified by 2-{(9S,10S,14R,18S)-18-(2-amino-2-oxoethyl)-14-[(5-methyl-1H -indol-1-yl)methyl]-8,17,20-trioxo-10-[4-(phosphonomethyl)phenyl]-7,16,19-triazaspiro[5.14]icos-11-en-9-yl}acetic acid ((14R)- 1b), ring-closing methathesis-derived macrocyclic tetrapeptide mimetics have recently been reported that bind with high affinity to Grb2 SH2 domains in both extracellular and whole-cell assays. The synthetic complexity of this class of agents limits further therapeutic development. Although a significant component of this synthetic complexity arises from the presence of three stereogenic centers, C(9) (S), C(10) (S), and C(14) (R), it is unclear whether stereoselective introduction of defined configuration at C(14) is required for high-affinity binding. Reported herein is a synthetic route to these macrocycles lacking stereoselectivity in the formation of the C(14) ring junction, which is four synthetic steps shorter than the original stereoselective synthesis. Separation of C(14)-epimers obtained by this approach was achieved by preparative HPLC. Molecular-dynamics studies of ligands bound to the Grb2 SH2 domain protein indicated that the (14R)-configuration should display more-favorable interactions with the protein relative to the (14S)-epimer. Indeed, although surface-plasmon-resonance-derived binding constants to Grb2 SH2 domain protein indicated that the affinity of the (14R)-epimer (KD=4.8,nM) is greater than that of the (14S)-epimer (KD=11,nM), it is only marginally so. Therefore, little affinity would be lost through a non-stereoselective synthesis of the C(14)-center. Further studies are in progress to explore reduced structural complexity at the C(14)-center. [source] rac -9-Ethyl-12a-hydroxytetradecahydrotriphenylene-1,5(2H,4bH)-dione: stabilization of a new isomer of a functionalized perhydrotriphenylene through a tandem Michael addition,aldol reactionACTA CRYSTALLOGRAPHICA SECTION C, Issue 6 2008Luis Arturo García The title compound, C20H30O3, is a new functionalized perhydrotriphenylene derivative formed via a tandem Michael addition,aldol reaction. The structural study reveals that the system of fused rings approximates a C2 point symmetry, with trans,cis,cis ring junctions, while highly symmetric all- trans perhydrotriphenylene, previously characterized, approximates a D3 symmetry. The perhydrotriphenylene nucleus of the title compound corresponds to the third stable stereoisomer isolated for this polycyclic system. Considering that the Cs isomer was obtained recently through a similar tandem reaction, a general strategy is proposed which may help to obtain other stable stereoisomers of perhydrotriphenylene. [source] 20-Hydroxyimino-5,-pregna-9(11),16-dien-3,-yl acetate and 17-oxo-5,-androst-9(11)-en-3,-yl acetateACTA CRYSTALLOGRAPHICA SECTION C, Issue 12 2000Héctor Novoa de Armas In the title compounds, C23H33NO3 and C21H30O3, respectively, the ester linkage in ring A is equatorial. In these steroids, the six-membered rings A and B have chair conformations, but ring C can be better described as a half-chair. The five-membered ring D adopts a 14,-envelop conformation. The A/B, B/C and C/D ring junctions are trans. [source] | ||||||||||