We present the application of several homo-and heteronuclear 1D-and 2D-NMR techniques to assign the 'H-NMR chemical shifts of the dominant conformation of didemnin B (2; three different conformations in (D,)DMSO solution in the ratio 8:l:l) and its conformational analysis, as well as the solution conformation of didemnin A (1). The conformations were refined by restrained molecular-dynamics calculations using the GROMOS program and by MOMO, a novel personal-computer-based interactive molecular-graphics and molecular-mechanics package, using experimental distances (via a H.. .H pseudo potential function) as restraints.The solution structures of 1 and 2 obtained by GROMOS and MOMO calculations were compared with each other and related to the recently solved crystal structure of 2. Focusing on the main conformer, the two kinds of the distance-restrained conformational calculations for 2 yielded a 'solution structure' close to the crystal structure. Almost all of the 40 restrained H...H distances coincided (within the estimated standard deviations) with those observed in the crystal structure. One more hydrogen bond was detected in solution involving the lactoyl OH group (disordered in the crystal structure) and the dimethyltyrosine (Me2TyrS) carbonyl 0-atom. The macrocyclic ring system in the modeled solution structure of 1 exhibited a topology close to those of the solution and crystal structures of 2. The main difference between 1 and 2 could be traced back to a significant change in the y angle of the N-methyl-o-leucine (MeLeu7) residue. In 1, the N-methyl moiety of MeLeu7 points inward within the macrocyclic ring toward the 1st and Hip region. We also tested the suitability of structures obtained from NMR data as 'search fragments' in the 'Patterson search approach of crystal-structure analysis. It proved possible to resolve the crystal structure of 2 aposteriori with the Patterson search program PATSEE, in this way.Introduction. -Didemnin A (1) and B (2); Fig. I belong to a new class of highly active antiviral cytotoxic depsipeptides which were isolated from a Caribbean tunicate of the family Didemnidae (Trididemnum genus), A first structural characterization was performed by degradative and some spectroscopic studies [l] [2]. The total synthesis of the didemnins [3] [4], the crystal structure of didemnin B (2) [5], and the assignment of all 'Hand 13C-NMR signals of didemnin A (1) in solution [6] have been published recently. The interesting spectrum of biological activities of the didemnins (discussed below) has prompted further research on their structural features in the solid state and in solution. A detailed knowledge of the conformations in different environments is required to understand the difference in the activity between didemnin A (1) and B (2).These cyclic depsipeptides are of great interest because of their effective inhibition of the replication of DNA and RNA viruses in vitro [2]. They are reported to be highly active in vim against P388 leukemia and B16 melanoma and potent inhibitors of the L...
(4u), x = c1 (4b). x = B r (4c), X = OAc (4d), X = OCH3 ( 4~1 , x = OH (3) reacts with a variety of compounds containing acidic hydrogen to form the ring-opened keto derivatives ( 4 ) . For instance, passage of gaseous hydrogen chloride into a solution of (3) immediately gives rise to (4a) [81, while gaseous hydrogen bromide affords (4bjr9l. A solution of (3) and acetic acid form the acetate (4c) r6al. (3) and methanol react to (4d) [91, which interestingly can also be prepared from ( 2 ) by debromination with a zinc-copper couple in methanol. (3) and water form (4e) [91, also obtainable in high yield directly from (2) by treatment with a zinc-copper couple in tetrahydrofuran-water (4 : 1 viv) at room temperature. (3) and D20 give rise to (4f); IH-NMR in dimethylformamide: -t = 8.95 (6H/br. s), T = 8.7 (6H/s). Generally, ring-opening of (3) is markedly accelerated by ZnBr2. The compounds ( 4 ) were identified by N M R spectroscopy and, when known, by comparison with authentic material.
Cyclopentddienylmeta1Icarbonyln~trosyl-carbenkomplexe C~H~MO(CO)(NO)C(R)C~H~ (1 ac, R = OCH3, OCzHs, N(CH3)z) reagieren mit Fe(C0)S bei UV-Bestrahlung unter ubertrdgung von ,,C(R)C&s" zu den Carbenkomplexen (C0)4FeC(R)C,jHs (3a-c). -Durch Ablnderung des bisher gebrauchlichen Syntheseverfahrens fur acyclische Ubergangsmetallcarbonyl-Carbenkomplexe -AusschluR von Wasser und Reaktionstemperaturen zwischen 0" und -60" -gelang es, auch auf diese Weise Verbindungen des Typs (C0)4FeC(OCzHs)R
HCyclopentadienyl-dicarbonyl-nitrosyle des Chroms, Molybdanq und Wolframs C5H5M(CO)2-NO (M -Cr, Mo, W) (la-c) addieren in Athcr aquimolare Mengen Phenyllithium. Die sich dabei bildenden Acylmetallate lassen sich durch Alkylierung mit Oxoniunitetrafluoroboraten (4d, e) zu den freien Carben-Koniplexen umsctzen. IR-, 'H-NMR-und massenspektroskopische Untersuchungen der stabilen, sublimierbaren, diamagnetischen CarbenKomplexe 5 zeigen, da13 der nucleophile Angriff von LiC6H5 nur an einer der beiden COGruppen stattfindet und das a-Donor/x-Akzeptor-Verhaltnis der verschiedenen CarbenLiganden sich charakteristisch auf die iibrigen am Zentralmetall gebundenen Liganden auswirkt. Durch Belichtung lassen sich die Carben-Liganden der Komplexe 5 auf Eisenpentacarbongl unter Bildung der entsprechenden (C0)4Fe-carben-Komplexe ubertragen. In der Reihe der Ubergangsmetall-carben-Komplexe substi tuierter Metallcarbonylez-4) sollte die Umsetzung der Cyclopcntadienyl-dicarbonyl-nitrosyle des Chroms, Molybdiins und Wolframs mit Organolithium-Verbindungen die Frage klaren, wo der 1) XXXI. Mitteil.: E. 0. Fischer und V. Kiener, J. organomet. Chem. 27, C 56 (1971).2 ) E. 0. Fiscfier und A. Maasbdl, Chem. Ber. 100, 2445 (1967).
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