Recombinant wild-type human IGF-1 and a C-region mutant in which residues 28-37 have been replaced by a 4-glycine bridge (4-Gly IGF-1) were secreted and purified from yeast. An IGF-1 analogue in which residues 29-41 of the C-region have been deleted (mini IGF-1) was created by site-directed mutagenesis and also expressed. All three proteins adopted the insulin-fold as determined by circular dichroism. The significantly raised expression levels of mini IGF-1 allowed the recording of two-dimensional NMR spectra. The affinity of 4-Gly IGF-1 for the IGF-1 receptor was approximately 100-fold lower than that of wild-type IGF-1 and the affinity for the insulin receptor was approximately 10-fold lower. Mini IGF-1 showed no affinity for either receptor. Not only does the C-region of IGF-1 contribute directly to the free energy of binding to the IGF-1 receptor, but also the absence of flexibility in this region eliminates binding altogether. As postulated for the binding of insulin to its own receptor, it is proposed that binding of IGF-1 to the IGF-1 receptor also involves a conformational change in which the C-terminal B-region residues detach from the body of the molecule to expose the underlying A-region residues.

AbstractThe X‐ray crystal structures of 2,11‐bis(di‐R‐phosphinomethyl)benzo[c]phenanthrenes (R = Ph, t‐Bu) are reported. Both ligands have the same conformation and the substitution of a Ph by a t‐Bu group does not cause significant changes in the tetracyclic aromatic unit which shows the same distortions as the parent hydrocarbon. The conformations and structural features of the two ligands and 18 complexes containing these ligands as well as of one compound with a ligand with Et substituents are compared. It is pointed out that (1) the conformations of the free ligands differ significantly from those of their complexes, (2) in all the complexes characterized to date, these ligands act as chelating agents, and (3) the ligands adopt two different conformations in the complexes, one of them appearing to be more flexible than the other.

Obtention de produits de C-nitrosation (methylamide d'acide N-R nitroformohydroximoyl formimidique (A)) et de C,N-dinitrosation ([methyl nitroso] amide d'acide formohydroximoyl N-R formimidique (B)); A est instable et se decompose en dimethylaminomethyl-5 furannemethanol-2 et en oxime de dihydro-5,6 methylamino-3 thiazine-1,4one-2 (C). Etude RX des composes B et C (R=[dimethylaminomethyl-5 furfurylthio]-2 ethyl)

Mr=364.9 , orthorhombic, P21212~, a-- 31.04 (6), b= 19.21 (4), c= 6.57 (3)/k, V= 3888.2/k 3, Z=8, D x=1.25Mgm -3, 2(CuKa--)= 1.54051/k, /~= 1.796 mm -~, F(000)= 1552, T= 293 K. Final R = 0.075 for 3766 observed reflexions. The absolute configuration was determined as RR. There are two crystallographically independent molecules which have different conformations in the propyl chain. Both molecules adopt a conformation intermediate between 'perpendicular-trans' and 'planar-trans'. Introduction. The crystal studied was that of one of the four isomers present in the adrenoceptor-blocking drug labetalol hydrochloride (Brittain, Drew & Levy, 1982). The single enantiomer ((a) 2°'5°c-29.2 °(MeOH, 5.1 g dm-3)) (Hartley, Lunts, Collins, Hallett, Clifton & Wicks, 1982) was shown to be >99% isomerically pure as determined by GLC (Munro, Hunt, Rowe & Evans, 1978). This compound crystallizes in at least two polymorphs, and the one studied here (I) had a melting point of 468-469 K. The structure analysis has shown the absolute configuration to be RR.

C17H22 N + . C I , M r = 275.82, monoclinic, P21, a = 5.56 (3), b = 9.97 (3), c = 14.41 (5) A, fl = 80.42 (2) ° from diffractometer measurements (Cu K~ radiation), V = 787.8 A a, Z = 2, D c = 1.16 Mg m -Z, F(000) = 320, ~ = 2.023 mm -~, approximate crystal dimensions 0.6 x 0.5 x 0.4 ram. Final R = 0.044 for 2289 observed reflexions. The absolute configuration is confirmed as S. Introduction. The resolution of racemic 1-methyl3-phenylpropylamine has been reported on three occasions by Dutch (van Dijk, Keizer & Moed, 1963), Russian (Potapov, Dem'yanovitch & Terent'ev, 1964), and Czech (Cervinka, Kroupova & Belovsky, 1968) workers. The Dutch and Czech groups attempted to establish the absolute configuration of the (+)enantiomer by degradation to compounds with known absolute configuration but they arrived at opposite conclusions. The Russians, by studying the optical rotatory dispersion curves of (+)-l-methyl-3-phenylpropylamine and its N-benzyl derivative, came to the same conclusion as the Dutch group that the (+)enantiomer has an S configuration. 0567-7408/82/010306-03501.00 In order to provide unequivocal evidence for this assignment the title compound (I) was prepared from (+)-l-methyl-3-phenylisopropylamine, by reductive alkylation with benzaldehyde in the presence of hydrogen and a platinum-on-carbon catalyst, followed by conversion into the hydrochloride. Recrystallization from ether-methylene chloride provided a crystal suitable for X-ray crystallography, m.p. 459-460 .5K, [a]~ ~°c 7 . 4 ° (c 5.7 g d m -3, MeOH). [The change in the sign of rotation occurred on forming the hydrochloride in an analogous manner to that observed in converting (+)-l-methyl-3-phenylisopropylamine {[a] o +2.7 ° (c 9.5 g dm -3 EtOH)} into (-)-l-methyl-3-phenylpropylamine hydrochloride {m.D. 386-387 K, In] D 7 . 2 ° (c 5.8 g dm -3, H20) (van Dijk et al., 1963)}.]

AbstractAusgehend vom Ester (I) wird ein (nichttrennbares) Gemisch der isomeren Säuren (IIa)+(IIb) erhalten; die hieraus zugänglichen (Li‐alanab) Reduktionsprodukte (IIc) bzw. (IId) (trennbares Gemisch) werden mit Peroxydodecansäure zu (Ile) bzw. (IIf) oxidiert, die bei der Thermolyse in Toluol (durch Cyclisierung intermediär gebildeter Sulfensiiure‐Stufen) die gewünschten diastereomeren Thietan‐S Oxide IIIIa)+(IIIb) bzw. (IIIc) + (IIId) (jeweils trennbares Gemisch) liefern.

Benzotropones 6 react with dienophiles 7 to give endo-adducts 8 as shown by PMR. Unlike similar ketones which usually undergo 1,3-acyl shifts or oxadi-π-methane rearrangements, these ethenobenzocycloheptenones 8, on direct or sensitized irradiation, lead to the di-π-methane rearrangement products 1H-benzo[f]cycloprop[cd]-indenones 9. The structures of the latter were elucidated by the use of Eu(FOD)3 and X-ray diffraction. Prolonged irradiation of tetrahydrofluorenone 19 a potential 1,3-acyl shift product of ethenobenzocycloheptenones, gave only dienyl aldehyde 21 in low conversion. These results suggest that the chemical pathway chosen in these reactions is dependent on geometrical and electronic factors.

C10H)sN4, M r = 192.2, monoclinic, P21/c, a = 7.90(3), b = 11.83 (4), c = 14.23 (8)A, fl = 56.75 (5) ° from diffractometer measurements (Mo/(6 radiation), V = 1112.2 A 3, Z = 4, D r = 1.15 Mg m -3, F(000) = 416, g = 0.042 mm -~, approximate crystal dimensions 0.8 x 0.4 x 0.2 mm. R = 0.068 for 1171 observed reflexions. The structure consists of hydrogen- bonded molecules IN(3)... N'(6) = 2.94 (1) AI. Introduction. The title compound (II) was recrystal- lized from ethyl acetate. Systematic absences indicated space group P21/c. Data were collected for hk0-12 with 0,,, x = 25 ° on a Stoe STADI-2 two-circle diffractometer (graphite-monoch romated Mo K~ radiation). This gave 1694 data of which 1171 unique reflexions with I > 30(I) were used in subsequent calculations. Lorentz and polarization corrections (but none for extinction or absorption) were applied, and the data sealed by a Wilson plot. The structure was solved by direct phasing methods with the SHELX 76 system of programs (Sheldrick, 1976), which was used for all calculations. Complex neutral-atomic scattering fac- tors were taken from International Tables for X-ray Crystallography (1974). Weighted full-matrix least- squares refinement (including constrained isotropic H atoms except H(3)) converged at R = 0.068 for 1171 observed reflexions (R = Y liFo i -iF~IlY IFol); Rw= 0.075 {R w = Y. (I IFol - IF~I I.w,/')/y (IFol.w'/2), w 558/(02(Fo) + 2.2 x 10 -4 F~o)}. A difference map and high temperature factors for the atoms concerned suggest that there is disorder in the H atoms of the two methyl substituents and in the propyl group (C(13), C(14) and attached H atoms). In the final cycle all shifts in parameters were less than their standard deviations. Positional parameters are given in Table 1 and bond distances and angles in Table 2.* A view of the molecule is shown in Fig. 1.

erythro- and threo-2-t-Butylthio-3-vinylnonan-1-ol have been prepared by Claisen rearrangement of the silylketen acetals derived from (E)-non-2-enyl t-butylthioacetate followed by reduction with lithium aluminium hydride. The sulphur function influenced the stereoselectivity of formation of the silylketen acetals which, in turn, determined the ratio of diastereoisomeric products obtained in the rearrangement. Thermolysis of erythro-2-t-butylsulphinyl-3-vinylnonan-l-ol at 140 °C for 5 min gave erythro-1-(hydroxymethyl)-2-vinyloctanesulphenic acid which cyclized spontaneously to a mixture of rel-(1R,2R,3S,4R)- and rel-(1R,2S,3R,4R)-3-hexyl-2-(hydroxymethyl)-4-methylthietan 1-oxide. threo-2-Butylsulphinyl-3-vinylnonan-1-ol under the same conditions gave a mixture of rel-(1R,2R,3R,4R)- and rel-(1R,2S,3S,4R)-3-hexyl-2-(hydroxymethyl)-4-methylthietan 1-oxide. Allocations of configuration to these thietan 1-oxide derivatives based on transition-state considerations have been substantiated by a determination of the crystal structure of the rel-(1R,2S,3R,4R)-isomer and by n.m.r. spectroscopy, which also led to tentative assignments of conformation.

AbstractAus 3‐Ethylthioimidazo(l ,5‐a)pyridin (Ia) entsteht eine Li‐Verbindung (Ib), die mit Benzonitril (II) zu den Folgeprodukten (III) bis (V) führt.

Thermal rearrangement of 1,3-dichloro-6-ethoxycarbonyl-2-thiabicyclo[3, 1, 0]hex-3-ene does not follow the anticipated course, but leads instead to ethyl-2,4-dichloro-5-hydroxy-6-methylbenzoate, whose structure has been confirmed by an X-ray crystal structure determination.

AbstractUntersuchungen an Humulen (I) und seinem 4,5‐Epoxid (II) werden im Zusammenhang mit der Synthese von Naturstoffen beschrieben.

1,4-Addition of sulphur nucleophiles to the diene (12) derived via the pen-2-em (5) from clavulanic acid provides the thiadeoxa analogues (14–15). X-ray analysis of the ester (14) shows the thermodynamically stable isomers to have the same relative stereochemistry as clavulanic acid.

The crystal structure of exo-7-hydroxybicyclo[3.3.1]nonan-3-one (III) and exo-7-methoxybicyclo[3.3.1]nonan-3-one (IV) have been determined. The structure of (III) shows distortions which may be caused either by partial 3,7-hydride transfer or by a disordered arrangement of undistorted dimers in the crystal. The structure of (IV) shows no unexpected distortions.

3-Ethylthioimidazo[1,5-a]pyridine reacts with butyl lithium followed by benzonitrile to give the new 10-π electron system, 1-phenyl-2,3-diazacycl[3,2,2]azine, possibly via 3,5-didehydroimidazo[1,5-a] pyridine.