01290nas a2200193   4500008004100000022001400041245012900055210006900184260011000253300001400363490000700377520046700384100003100851700002300882700002300905700001700928700002100945856013000966       2013                        eng d  a1359-734500aSynthesis of palmyrolide A and its cis-isomer and mechanistic insight into trans-cis isomerisation of the enamide macrocycle0 aSynthesis of palmyrolide A and its cisisomer and mechanistic ins  aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcMAR  a3342-33440 v493 a<p>Concise and protecting-group free synthesis of ent-palmyrolide A and (-)-cis-palmyrolide A were achieved starting from commercially available (S)-citronellal. The key fragment of palmyrolide A, ``(5S,7S)-7-hydroxy-5,8,8-trimethylnonanamide'', which makes up the most challenging part of the target molecule, was prepared in just three steps. A plausible mechanism for the trans-cis isomerization of the double bond in the macrocycle has been investigated.</p>1 aPhilkhana, Satish, Chandra1 aSeetharamsingh, B.1 aDangat, Yuvraj, B.1 aVanka, Kumar1 aReddy, Srinivasa  uhttps://library.ncl.res.in/content/synthesis-palmyrolide-and-its-cis-isomer-and-mechanistic-insight-trans-cis-isomerisation-001880nas a2200169   4500008004100000245012000041210006900161260000800230300001400238490000700252520122400259100003101483700002101514700002301535700002101558856013101579       2016                        eng d00aSynthesis and biological evaluation of palmyrolide a macrocycles as sodium channel blockers towards neuroprotection0 aSynthesis and biological evaluation of palmyrolide a macrocycles  cAUG  a8457-84730 v143 a<p>Palmyrolide A is a neuroprotective macrolide isolated by Gerwick and coworkers in 2010. This natural product is known to suppress neuronal spontaneous calcium ion oscillations through its voltage-gated sodium channel blocking ability which is of significant interest in CNS drug discovery. Herein, we give a detailed account on total synthesis of (+)-palmyrolide A and synthesis of a focused library of macrocycles around the scaffold, followed by their biological evaluation. Use of the chiral pool approach, Zhu's oxidative homologation, access to unnatural cis-palmyrolide A, preparation of 18 new analogues and identification of macrolides with improved sodium channel blocking activity are the important features of the present paper. As a measure of potency as voltage-gated sodium channel blockers, all the synthesized analogues were profiled for their ability to inhibit the veratridine-stimulated Na+ influx in murine primary neuronal cultures. Four macrocycles were found to be more potent or comparable to that of the natural product (-)-palmyrolide A. The most potent compound from this series 20 was structurally simplified and readily accessible in good quantities for further biological profiling.</p>1 aPhilkhana, Satish, Chandra1 aMehrotra, Suneet1 aMurray, Thomas, F.1 aReddy, Srinivasa  uhttps://library.ncl.res.in/content/synthesis-and-biological-evaluation-palmyrolide-macrocycles-sodium-channel-blockers-towards