A sequence that is represented frequently in functionally important sites involving protein-DNA interactions is GTG/CAC, suggesting that the trimer may play a role in regulatory processes. The 2.5 A resolution structure of d(CGGTGG)/d(CCACCG), a part of the interior operator (OI, nucleotides +44 to +49) of the gal operon, co-crystallized with spermine, is described herein. The crystal packing arrangement in this structure is unprecedented in a crystal of B-DNA, revealing a close packing of columns of stacked DNA resembling a 5-stranded twisted wire cable. The final structure contains one hexamer duplex, 17 water molecules and 1.5 spermine molecules per crystallographic asymmetric unit. The hexamer exhibits base-pair opening and shearing at T.A resulting in a novel non-Watson-Crick hydrogen-bonding scheme between adenine and thymine in the GTG region. The ability of this sequence to adopt unusual conformations in its GTG region may be a critical factor conferring sequence selectivity on the binding of Gal repressor. In addition, this is the first conclusive example of a crystal structure of spermine with native B-DNA, providing insight into the mechanics of polyamine-DNA binding, as well as possible explanations for the biological action of spermine.
Two analogs of podophyllotoxin, with the same absolute stereochemistry as the natural product, have been synthesized from the cycloadduct between a-hydroxy-a'-phenyl-o-quinodirnethane and the furnarate of S-methyl lactate. After initial attempts to produce the cycloadduct from photochemically generated a-hydroxy-a'-phenyl-o-quinodirnethane failed, a study of the thermal generation and reaction of a-hydroxy-o-quinodirnethane with the fumarate and acrylate of S-methyl lactate was made. A comparison was made of the diastereoselectivity of these cycloaddition reactions to those previously reported, in which the o-quinodirnethane was generated photochemically. The a-hydroxy-o-quinodirnethane was produced both by the known thermolysis of benzocyclobutenol and by therrnolysis of l-hydroxy-l,3-dihydrobenzo[c]thiophene-2,2-dioxide. The diastereorneric excess for the cycloaddition reactions was found to be greater than 95% with modest (ca. 55%) isolated yields of the major cycloadducts. Following these model studies, it was found that a-hydroxy-a'-phenyl-o-quinodirnethane produced thermally from l-hydroxy-3-phenyl-1,3-dihydrobenzo[c]thiophene-2,2-dioxide could be added to the furnarate of S-methyl lactate with high diastereoselectivity and good yield. The product of this reaction was converted to the podophyllotoxin analogs 7 and 17. Utilisant le cycloadduit obtenu par condensation de I'a-hydroxy-a'-phtnyl-o-quinodirnkthane et du fumarate du lactate de S-rnCthyle, on a synthCtisC deux analogues de la podophyllotoxine possCdant la m&rne stCrCochirnie que le produit naturel. I1 n'a pas Ct C possible de produire le cycloadduit B partir de l'a-hydroxy-a'-phenyl-o-quinodimkthane obtenu photochirniquernent; on a donc utilist une rnkthode thermique pour gCnCrer I'a-hydroxy-o-quinodirnCthane et pour rCaliser sa rCaction avec le furnarate du lactate de S-rnCthyle. On a effectuk une cornparaison de la diastkrCosClectivitC de ces rCactions de cycloaddition avec celles rapportCes antkrieurernent, alors que 1'0-quinodirnethane avait CtC gCnerC d'une f a~o n photochirnique. L'-a-hydroxy-oquinodirnkthane a CtC obtenu par la thermolyse connue du benzocyclobutCno1 ainsi que par la therrnolyse du 1-hydroxy-1,3-dihydrobenzo[c]thiophkne-2,2-dioxyde. On a trouvC que l'excks de diastCrCornkres eit plus grand que 95% alors que le rendernent en cycloadduits principaux isolCs n'est que de 55%. A la suite de ces Ctudes rnodkles, on a trouvC que I 'a-hydroxy-a'-phCnyl-o-quinodirnkthane obtenu therrniquernent B partir du l-hydroxy-3-phCnyl-l,3-dihydrobenzo[c]thiophkne-2,2-dioxyde peut &tre addition& au furnarate du lactate de S-rnkthyle avec une excellente diasterkosklectivitC et un excellent rendernent. Le produit de cette rkaction peut &tre transform6 dans les analogues 7 et 17 de la podophyllotoxine.Mots clis : o-quinodirnkthanes, asyrnetrique, Diels-Alder, lactate, podophyllotoxine, lignane.[Traduit par la revue] Introduction The synthesis of aryl tetralin ligans such as dimethyl isolariciresinol or podophyllotoxin requires the stereoselective a...
. 67, 574 (1989).The cycloaddition of a-hydroxy orthoquinodimethane, generated photochemically from 2-methylbenzaldehyde, to the fumarate and acrylate of S-methyl lactate has been found to give a single diastereomer with high asymmetric induction (>95% de). This reaction provides a new and versatile synthetic route to substituted tetralins of high optical purity. A trans stereochemistry between the vicinal hydroxyl and carboxylactyl groups has been established for these cycloadducts. This is in contrast to previous work where cis stereochemistry has always been found for major cycloadducts of a-hydroxy o-QDMs. The high asymmetric induction, unusual diastereoselectivity, and the potential use of these reactions in asymmetric synthesis are discussed. On a observC que la cycloaddition de l'a-hydroxy orthoquinodimCthane, obtenu d'une f a~o n photochimique a partir du mCthyl-2 benzaldkhyde, sur le fumarate et sur l'acrylate du lactate de S-mCthyle conduit a un seul diastCriorntre avec une induction asymktrique Clevte (>95% de). Cette rCaction s'avkre &re une route de synthese nouvelle et versatile vers les tetralines substitubes de puretk optique ClevCe. On a Ctabli que les groupements hydroxyle et carboxylactyle vicinaux de ces cycloadduits sont de stCrCochimie trans. Ce rtsultat est en opposition avec ceux obtenus au cours de travaux antCrieurs alors qu'on a toujours obtenu une stCrCochimie cis pour les cycloadduits principaux des a-hydroxy o-QDM. On discute de I'induction asymktrique tlevte, de la diastCrCostlectivitC inhabituelle et des usages possibles de ces reactions en syntheses asymCtriques.Mots cle's : o-quinodimkthanes, Diels-Alder, asymCtrique, cycloaddition, induction, diastCrCosClective.[Traduit par la revue] Introduction Developing strategies towards the synthesis of enantiomerically pure compounds is one of the goals of modem organic chemistry and the study of asymmetric Diels-Alder reactions exemplifies the pursuit of this goal (1-5). The corresponding study of asymmetric Diels-Alder reactions of orthoquinodimethanes (0-QDMs) has received much less attention although o-QDMs have been extensively utilized as intermediates in non-asymmetric syntheses of chiral molecules (6). The addition of asymmetric control to the cycloaddition reactions of o-QDMs would provide a route to a large number of optically active compounds of interest. While a few examples of the intermolecular addition of chiral o-QDMs to achiral dienophiles have been published (6-9), only one example of a chiral dienophile reacting with an achiral o-QDM has been published (10). A possible reason for the lack of reports of asymmetric DielsAlder reactions of o-QDMs is that high diastereoselectivity in such reactions is often achieved only in the presence of Lewis acid catalysts. Such catalysts are frequently incompatible with the conditions required to generate the transitory and very reactive o-QDMs.Because of our interest in the use of o-QDMs in synthesis we have searched the literature to find chiral dienophiles that give high diastereo...
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