01405nas a2200241   4500008004100000022001400041245012000055210006900175260010600244300001400350490000700364520046500371653002100836653002500857653001900882653001600901653001700917100002900934700002600963700002700989700002101016856012601037       2014                        eng d  a0040-403900aEfforts towards the synthesis of microsporin B: ready access to both the enantiomers of the key amino acid fragment0 aEfforts towards the synthesis of microsporin B ready access to b  aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcAUG  a4777-47790 v553 a<p>Both the isomers methyl-(2S,8R)-2-((tert-butoxycarbonyl)amino)-8-hydroxydecanoate and methyl-(2S,8S)-2-((tert-butoxycarbonyl)amino)-8-hydroxydecanoate of an unusual amino acid residue and the key fragment of microsporin B are prepared. The key steps include cross metathesis and enzymatic kinetic resolution. In addition, a linear tetrapeptide with desired components towards total synthesis is also reported. (C) 2014 Elsevier Ltd. All rights reserved.</p>10aCross metathesis10aEnzymatic resolution10aHDAC inhibitor10aMicrosporin10aTetrapeptide1 aSwaroop, Pandrangi, Siva1 aTripathy, Sibanarayan1 aJachak, Gorakhnath, R.1 aReddy, Srinivasa  uhttps://library.ncl.res.in/content/efforts-towards-synthesis-microsporin-b-ready-access-both-enantiomers-key-amino-acid-001263nas a2200217   4500008004100000022001400041245013600055210006900191260007500260300001400335520042400349653001100773653001600784653002300800653001400823653001500837100001800852700002700870700002100897856012700918       2015                        eng d  a1434-193X00aBreaking and making of rings: a method for the preparation of 4-quinolone-3-carboxylic acid amides and the expensive drug ivacaftor0 aBreaking and making of rings a method for the preparation of 4qu  aPOSTFACH 101161, 69451 WEINHEIM, GERMANYbWILEY-V C H VERLAG GMBHcDEC  a7433-74373 a<p>A simple and convenient method to access 4-quinolone-3-carboxylic acid amides from indole-3-acetic acid amides through one-pot oxidative cleavage of the indole ring followed by condensation (Witkop-Winterfeldt type oxidation) was explored. The scope of the method was confirmed with more than 20 examples and was successfully applied to the synthesis of the drug Ivacaftor, the most expensive drug on the market.</p>10aAmides10aDrug design10aFused-ring systems10aOxidation10aOzonolysis1 aVasudevan, N.1 aJachak, Gorakhnath, R.1 aReddy, Srinivasa  uhttps://library.ncl.res.in/content/breaking-and-making-rings-method-preparation-4-quinolone-3-carboxylic-acid-amides-and-001365nas a2200265   4500008004100000022001400041245008700055210006900142260010600211300001400317490000700331520039500338653002500733653002500758653001500783653002100798653002000819100003100839700002700870700002200897700002200919700002200941700002100963856011500984       2015                        eng d  a0040-403900aFirst synthesis of nitrosporeusines, alkaloids with multiple biological activities0 aFirst synthesis of nitrosporeusines alkaloids with multiple biol  aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcMAR  a1252-12540 v563 a<p>Synthesis of nitrosporeusines A and B, thioester-bearing alkaloids from the Arctic Streptomyces nitrosporeus with exceptional biological activity is disclosed for the first time. In addition, we have prepared another biologically important natural product, maleimycin, in optically pure form using a gram-scale enzymatic resolution method. (C) 2015 Elsevier Ltd. All rights reserved.</p>10aEnzymatic resolution10aInfluenza H1N1 virus10aMaleimycin10aMichael reaction10aNitrosporeusine1 aPhilkhana, Satish, Chandra1 aJachak, Gorakhnath, R.1 aGunjal, Vidya, B.1 aDhage, Nagsen, M.1 aBansode, Ajay, H.1 aReddy, Srinivasa  uhttps://library.ncl.res.in/content/first-synthesis-nitrosporeusines-alkaloids-multiple-biological-activities-001731nas a2200289   4500008004100000022001400041245009400055210006900149260007100218300001400289490000600303520071400309653002101023653002101044653002801065653001601093653001901109100002701128700001801155700002101173700002501194700002501219700002201244700002601266700002101292856012801313       2015                        eng d  a1948-587500aSilicon incorporated morpholine antifungals: design, synthesis, and biological evaluation0 aSilicon incorporated morpholine antifungals design synthesis and  a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcNOV  a1111-11160 v63 a<p>Known morpholine class antifungals (fenpropimorph, fenpropidin, and amorolfine) were synthetically modified through silicon incorporation to have 15 sila-analogues. Twelve sila-analogues exhibited potent antifungal activity against different human fungal pathogens such as Candida albicans, Candida glabrata, Candida tropicalis, Cryptococcus neoformans, and Aspergillus niger. Si la-analogue 24 (fenpropimorph analogue) was the best in our hands, which showed superior fungicidal potential than fenpropidin, fenpropimorph, and amorolfine. The mode of action of sila-analogues was similar to morpholines, i.e., inhibition of sterol reductase and sterol isomerase enzymes of ergosterol synthesis pathway.</p>10aAntifungal drugs10aCandida albicans10aergosterol biosynthesis10amorpholines10asila-analogues1 aJachak, Gorakhnath, R.1 aRamesh, Remya1 aSant, Duhita, G.1 aJorwekar, Shweta, U.1 aJadhav, Manjusha, R.1 aTupe, Santosh, G.1 aDeshpande, Mukund, V.1 aReddy, Srinivasa  uhttps://library.ncl.res.in/content/silicon-incorporated-morpholine-antifungals-design-synthesis-and-biological-evaluation-001353nas a2200205   4500008004100000022001400041245010200055210006900157260007100226300001400297490000700311520055800318100001800876700002700894700002500921700002600946700002400972700002100996856013001017       2016                        eng d  a1523-706000aTotal synthesis of the marine natural product solomonamide B necessitates stereochemical revision0 aTotal synthesis of the marine natural product solomonamide B nec  a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcJUL  a3178-31810 v183 a<p>The first total synthesis of the proposed structure of solomonamide B has been achieved. However, the H-1 and C-13 NMR spectral data of the synthesized compound was not exactly matching with that of the natural solomonamide B. This prompted us to revise the originally proposed structure, in particular, the stereochemistry of the nonpeptide part, which was confirmed by its total synthesis. During the course of the synthesis, we have developed an interesting hydroxy group directed Wacker oxidation of internal olefins in a macrocyclic setting.</p>1 aKashinath, K.1 aJachak, Gorakhnath, R.1 aAthawale, Paresh, R.1 aMarelli, Udaya, Kiran1 aGonnade, Rajesh, G.1 aReddy, Srinivasa  uhttps://library.ncl.res.in/content/total-synthesis-marine-natural-product-solomonamide-b-necessitates-stereochemical-revision02000nas a2200193   4500008004100000245011000041210006900151260000800220300001100228490000800239520128500247100003101532700002701563700002701590700002101617700001801638700002101656856012901677       2017                        eng d00aIdentification of new anti-inflammatory agents based on nitrosporeusine natural products of marine origin0 aIdentification of new antiinflammatory agents based on nitrospor  cJUL  a89-1090 v1353 aNitrosporeusines A and B are two recently isolated marine natural products with novel skeleton and exceptional biological profile. Interesting antiviral activity of nitrosporeusines and promising potential in curing various diseases, evident from positive data from various animal models, led us to investigate their anti-inflammatory potential. Accordingly, we planned and synthesized nitrosporeusines A and B in racemic as well as enantiopure forms. The natural product synthesis was followed by preparation of several analogues, and all the synthesized compounds were evaluated for in vitro and in vivo anti-inflammatory potential. Among them, compounds 25, 29 and 40 significantly reduced levels of nitric oxide (NO), reactive oxygen species (ROS) and pro-inflammatory cytokines. In addition, these compounds suppressed several pro-inflammatory mediators including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF -kappa B), and thereby can be emerged as potent anti-inflammatory compounds. Furthermore, all possible isomers of lead compound 25 were synthesized, characterized and profiled in same set of assays and found that one of the enantiomer (-)-25a was superior among them. (C) 2017 Elsevier Masson SAS. All rights reserved.1 aPhilkhana, Satish, Chandra1 aVerma, Abhishek, Kumar1 aJachak, Gorakhnath, R.1 aHazra, Bibhabasu1 aBasu, Anirban1 aReddy, Srinivasa  uhttps://library.ncl.res.in/content/identification-new-anti-inflammatory-agents-based-nitrosporeusine-natural-products-marine02161nas a2200193   4500008004100000022001400041245013700055210006900192260000800261490000700269520141000276100002701686700002701713700002701740700003101767700002101798700001801819856013001837       2018                        eng d  a1935-273500a Nitrosporeusine analogue ameliorates Chandipura virus induced inflammatory response in CNS via NF kappa b inactivation in microglia0 aNitrosporeusine analogue ameliorates Chandipura virus induced in  cJUL0 v123 aChandipura Virus (CHPV), a negative-stranded RNA virus belonging to the Rhabdoviridae family, has been previously reported to bring neuronal apoptosis by activating several factors leading to neurodegeneration. Following virus infection of the central nervous system, microglia, the ontogenetic and functional equivalents of macrophages in somatic tissues gets activated and starts secreting chemokines, thereby recruiting peripheral leukocytes into the brain parenchyma. In the present study, we have systemically examined the effect of CHPV on microglia and the activation of cellular signalling pathways leading to chemokine expression upon CHPV infection. Protein and mRNA expression profiles of chemokine genes revealed that CHPV infection strongly induces the expression of CXC chemokine ligand 10 (CXCL10) and CC chemokine ligand 5 (CCL5) in microglia. CHPV infection triggered the activation of signalling pathways mediated by mitogen-activated protein kinases, including p38, JNK 1 and 2, and nuclear factor kappa B (NF-kappaB). CHPV-induced expression of CXCL10 and CCL5 was achieved by the activation of p38 and NF-kappaB pathways. Considering the important role of inflammation in neurodegeneration, we have targeted NF-kappaB using a newly synthesised natural product nitrosporeusine analogue and showed incapability of microglial supernatant of inducing apoptosis in neurons after treatment.1 aVerma, Abhishek, Kumar1 aWaghmare, Trushnal, S.1 aJachak, Gorakhnath, R.1 aPhilkhana, Satish, Chandra1 aReddy, Srinivasa1 aBasu, Anirban  uhttps://library.ncl.res.in/content/nitrosporeusine-analogue-ameliorates-chandipura-virus-induced-inflammatory-response-cns-nf01773nas a2200217   4500008004100000022001400041245014900055210006900204260000800273300001400281490000700295520096500302100002701267700002501294700001901319700002701338700002101365700002201386700002101408856012601429       2018                        eng d  a1477-052000aTotal synthesis of the potent anti-inflammatory natural product solomonamide A along with structural revision and biological activity evaluation0 aTotal synthesis of the potent antiinflammatory natural product s  cDEC  a9138-91420 v163 aHerein, we report the total synthesis of solomonamide A along with its structural revision for the first time. The natural product possesses very potent anti-inflammatory activity, and it contains a macrocyclic peptide having four consecutive stereocenters on an unnatural amino acid component. The key features in the present synthesis include the application of an Evans aldol reaction, ligand-free Heck macrocyclization and chemoselective oxidations. The challenging task of fixing the stereochemistry of OH at the C5-position was accomplished with the help of DFT calculations, applying a quantum-mechanical (QM)/NMR combined approach. Biological evaluation in a mouse paw edema model revealed that a low dose (0.3 mg kg(-1)) of the synthesized solomonamide A showed 74% reduction at 6 h, which was comparable to a high dose (10 mg kg(-1)) standard drug dexamethasone effect (75% at 6 h). Thus, we further confirmed the revised structure of solomonamide A.1 aJachak, Gorakhnath, R.1 aAthawale, Paresh, R.1 aAgarwal, Heena1 aBarthwal, Manoj, Kumar1 aLauro, Gianluigi1 aBifulco, Giuseppe1 aReddy, Srinivasa  uhttps://library.ncl.res.in/content/total-synthesis-potent-anti-inflammatory-natural-product-solomonamide-along-structural01405nas a2200229   4500008004100000022001400041245006500055210006500120260000800185520069100193653001600884653001800900653001700918653001600935653002000951100002700971700002500998700002101023700001801044700002101062856009201083       2019                        eng d  a1861-472800aAccess to a stereoisomer library of solomonamide macrocycles0 aAccess to a stereoisomer library of solomonamide macrocycles  cOCT3 a<p>In an attempt towards understanding stereo-structure activity relationships (SSARs), we have prepared eight possible stereoisomers of solomonamide macrocycles, in particular, by changing the stereochemical pattern of non-peptide fragment AHMOA. Here, we have demonstrated different ways to construct three contiguous chiral centers present in solomonamide B macrocycle using substrate/reagent-controlled methods. These methods involve Brown crotylation, NHK reaction and Evans aldol addition as key steps to synthesize key non-peptide fragment. Further, these non-peptide fragments were converted to their corresponding macrocycles via ligand-free intramolecular Heck reaction.</p>
10aCrotylation10aHeck reaction10aInflammation10aMacrocycles10aStereochemistry1 aJachak, Gorakhnath, R.1 aAthawale, Paresh, R.1 aChoudhury, Rahul1 aKashinath, K.1 aReddy, Srinivasa  uhttps://library.ncl.res.in/content/access-stereoisomer-library-solomonamide-macrocycles01129nas a2200241   4500008004100000022001400041245007400055210006900129260000900198300001400207490000900221520036100230653001800591653001500609653002300624653001600647100002700663700002300690700001900713700002800732700002100760856010600781       2021                        eng d  a1434-193X00aSynthesis and biological evaluation of hoshionolactam-based compounds0 aSynthesis and biological evaluation of hoshionolactambased compo  cAPR   a2212-22180 v20213 aIn search of novel antitrypanosomal agents based on hoshinolactam (IC50=3.9 nM), we disclose the synthesis and biological evaluations of 14 different analogues of the natural product using combinations of different acids and lactams. Antitrypanosomal activity assays revealed that the synthesized analogues were less potent than the parent natural product.10aHoshinolactam10aOzonolysis10aParasitic diseases10aTrypanosoma1 aJachak, Gorakhnath, R.1 aElizebath, Drishya1 aShukla, Anurag1 aShanmugam, Dhanasekaran1 aReddy, Srinivasa  uhttps://library.ncl.res.in/content/synthesis-and-biological-evaluation-hoshionolactam-based-compounds01515nas a2200253   4500008004100000022001400041245006700055210006400122260000800186300001500194490000900209520070300218653001600921653003500937653002100972653002900993653002001022100002101042700002701063700002601090700002601116700002101142856009801163       2022                        eng d  a1434-193X00aTotal synthesis of 12, 13-dibenzyl-banistenoside B and analogs0 aTotal synthesis of 12 13dibenzylbanistenoside B and analogs  cMAY  ae2022002220 v20223 a<p>
	Banistenosides A and B possessing a unique ``azepino(1,2-a)tetrahydro-beta-carboline'' carbon framework were isolated from the stem of Banisteriopsis caapi and showed MAO-A inhibition. Herein, we report the total synthesis of dibenzyl derivative of the untouched natural product in the last two decades, Banistenoside B. The key steps involve construction of 6.5.6.7 tetracyclic core using Pictet-Spengler reaction and intramolecular amide coupling. The stereoselective glycation was achieved through Hotha's protocol using gold catalyst, and silver triflate in the late stage of synthesis. The stereochemistry of most of the essential compounds were confirmed by X-ray crystallography.</p>
10aAu-catalyst10aMultiple steps total synthesis10aNatural products10aPictet-Spengler reaction10aWittig reaction1 aPatil, Suhag, S.1 aJachak, Gorakhnath, R.1 aKrishna, Gamidi, Rama1 aArgade, Narshinha, P.1 aReddy, Srinivasa  uhttps://library.ncl.res.in/content/total-synthesis-12-13-dibenzyl-banistenoside-b-and-analogs02381nas a2200241   4500008004100000022001400041245014100055210006900196260000900265300001600274490000700290520150900297100002701806700001801833700001801851700002501869700002101894700002801915700001901943700002701962700002101989856012902010       2023                        eng d  a0022-326300aComprehensive study on solomonamides: total synthesis, stereochemical revision, and SAR studies toward identification of simplified lead0 aComprehensive study on solomonamides total synthesis stereochemi  cDEC   a17088-171330 v883 a<p>
	Solomonamides, a pair of macrocyclic peptide natural products originating from marine sources, have garnered significant attention within the synthetic community owing to their marked anti-inflammatory efficacy and intricate molecular architectures. In this paper, we present a very detailed investigation into solomonamides, including the challenges associated with the total synthesis, the evolution of our synthetic strategies, structural reassignment, synthesis of all possible stereoisomeric macrocycles, biological assessment, structure-activity relationship (SAR) studies, etc. Within the ambit of this total synthesis, diverse strategies for macrocyclization were rigorously explored, encompassing the Friedel-Crafts acylation, cyclization involving the aniline NH2 moiety, macrolactamization utilizing Gly-NH2, and Heck macrocyclization methodologies. In addition, an array of intriguing chemical transformations were devised, including but not limited to photo-Fries rearrangement, Wacker oxidation, ligand-free Heck macrocyclization, oxidative cleavage of indole, synthesis of contiguous stereocenters via substrate/reagent-controlled protocols, and simultaneous making and breaking of olefinic moieties. The findings of this investigation revealed a structurally simplified lead compound. Remarkably, the lead compound, while possessing structural simplification in comparison to the intricate solomonamide counterparts, demonstrates equipotent in vivo anti-inflammatory efficacy.</p>
1 aJachak, Gorakhnath, R.1 aKashinath, K.1 aVasudevan, N.1 aAthawale, Paresh, R.1 aChoudhury, Rahul1 aDange, Santoshkumar, S.1 aAgarwal, Heena1 aBarthwal, Manoj, Kumar1 aReddy, Srinivasa  uhttps://library.ncl.res.in/content/comprehensive-study-solomonamides-total-synthesis-stereochemical-revision-and-sar-studies