Ischemic ARF is accompanied by marked alterations in the expression of key enzymes of the nitric oxide pathway, indicative for deficiency of constitutive NOS activity. l-Arg supplementation reduces O2- generation and significantly improves the expression of nitric oxide signaling proteins as well as the recovery phase of ischemic ARF.
Background:L-Arginine (L-Arg), a substrate of nitric oxide synthases, improves renal function in ischemic acute renal failure (iARF). We evaluated whether L-Arg improves renal morphology and cell survival in the course of iARF. Methods and Results: iARF was induced in rats by bilateral clamping of renal arteries for 45 min. L-Arg was applied intraperitoneally during clamping, and orally during 14 days of follow-up. Morphology and cell survival of renal cortical and medullar tissue was analyzed on days 1, 3, 7, and 14 of follow-up, using toluidine blue staining and immunohistochemistry of perfusion-fixated tissue, and Western blot analysis of tissue homogenate. Renal tubular injury showed typical features of necrosis and was most severe on days 1 and 3 after clamping, predominantly in S3 segments, with almost complete recovery by day 14. Enhanced medullar monocyte infiltration, determined by ED-1 expression as well as by immunohistochemistry, and enhanced expression of proliferating cell nuclear antigen (PCNA), indicative of proliferation and regeneration, accompanied these morphological changes. Compared to controls, L-Arg had no impact on renal morphology, ED-1, and PCNA expression. Furthermore, expression of markers of apoptosis Bcl-2, Bax, and cleaved caspase-3 was only slightly increased in iARF rats, compared to sham-operated animals, and was also not influenced by L-Arg. Conclusion: Despite its repeatedly reported positive impact on renal function as also shown in our model, L-Arg does not alter cell death and proliferation in the course of iARF in our model. Thus, different mechanisms have to be considered, in particular improved intrarenal hemodynamics.
Starting from 1-[(tert-butoxy)carbonyl]piperidine-4-carboxylic acid and 2-bromoaniline, the spiro[indole-3,4'-piperidin]-2-one system was obtained in three high-yielding steps: anilide formation, N(1)-protection, and intramolecular cyclization under Pd catalysis as the key reaction. The preparation of the corresponding 2bromoanilide was studied. In extension, the same sequence was developed with 4-methyl-and 4-nitro-2bromoaniline. In the key step, the NO 2 group led to a rather diminished yield. The transformation of the protected spiro[indole-3,4'-piperidin]-2-one to the corresponding unprotected dihydroindoles is discussed.
Abstra~t--Total syrlthescs of corynarithe alkaloids including eighc possible stcreoisomcrs of isosilsirikincs alone with corvrrantheine a n d hirsuteine according t o two different approaches n r e describcd, thcrehy UnambigUoUSly solved the pending problcms on thc stercoctlenlistry of these alkaloids. 1XNEIIAL ISFOIlMI\TIOKThe corynanthe-typc :alkaloids are of particular intcrest to the synchetic ctiemisl.for various reasons. First of all they rcprrsent a quite inrge subgroup of Lhc indolc alkaioids which additionally is o i special interest from the biogenetic point of uiew,l-" as they are very early located in the bioeenetic sequcnce lschcmc 1). Compounds like geissoschizine I and ajmalicine 2 still very nicely r e i l c c t thc combirratioi> o r tryplaminc o r tryptophan with thc terpcnoid C-10 unit secologanin (3). A mare detailed discussion on the relationship between the con-Piguration and conformation of crucial biogcnetic precursors a n d the design of key intermediates f o r this synthetic P~O ,~E C I . as well as the stereoselcctivity a n d ster~ospecificity of their decisive transformations will bc postponed, howcvcr, Lo a later stage after the outcosle o f these processes has been revealed. Z 1 6 -E p i -2 -i s o s i t s i r i k i n e -----9 OH 6 B z unknown---------------------10SuTCice it to say that at the beginning of synthetic efforts in this direction no stercoselcctive method was available to solve this problcm in the quinolixidine S C T~C S . In the meantime particularly owing to synthetic efforts aiming at gcisso-schizine4-" this situation has been changed completely as very efficient and reliable ter:hniqucs have been developed particularly by 0verman7 hhile the methylene-lactam rearrangement of 12 to i S developed particularly by our l l a n n o v e r groupn provcd to be "cry uscfui in this field8.= (Scheme 2 ) . Recently, an efficient methode.lo for construction of thc stcreoisomer 14 has bcen established by HETEROCYCLES, Vol 30, No. 2, 1990combination of two interesting reactions which are enamide photocyclization and climiilation-addition reaction of furopyridone by the Kobe group." Additionally.the Kobe group has very recently established the useful olcfinic isomerlzation from the stable E-isomer 14 even to the unstablc i s o m e r 1 3 though the Hannover group had alrcady reported" one-way isomerization of the unstable Z-oiefin 13a to thc stable E-olcfin 1 4 . Thus the importance of thc two lactams 1 3 and 14 a s key and versatile intermediates in the synthesis of target alkaloids has become clear.it is assumed that thc ethylidene-lactams having Eor %-conIiguration at the cxocyclic double bond would be converted into the rcspective Zor E-counterparts.upon olefinic isomeriration and additional epimerization at the C-3 position from B to u (13-15 and 14-1 6 ) would furnish two sets of isomeric lactams depending on the configurations at C -3 and C -1 9 , thereby providing the possibility to synthesize all eight stereoisomcrs of isositsirikines with rcspcct to C -3 , 1 5 , 16. and 1 9 fro...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.