Conformation of a biologically active C-terminal hexapeptide analog of the pheromone biosynthesis activating neuropeptide by NMR spectroscopy.

The solution conformation of a biologically active C-terminal hexapeptide analog of the pheromone biosynthesis activating neuropeptide Tyr-D-Phe-Ser-Pro-Arg-Leu-NH2 has been studied by NMR spectroscopy. A beta-turn conformation was identified from the NOE connectivities observed for the peptide in a mixed solvent of water and DMSO, indicating that this is the biologically active conformation of the peptide. This study also suggests that the use of such an aqueous-like solvent mixture allows the observation of a preferred conformation for small linear peptides in the presence of conformational averaging.

Structure of 3-methyl-1,2,3,4,5,6-hexahydro-1,6-methano-3-benzazocinium hydrogen oxalate.

C13H18N+.C2HO4-, Mr = 277.3, orthorhombic, P2(1)2(1)2(1), a = 5.752 (1), b = 15.502 (2), c = 15.910 (2) A, V = 1418.6 (6) A3, Z = 4, Dx = 1.298 g cm-3, Mo K alpha (lambda = 0.71069 A), mu = 1.01 cm-1, F(000) = 592, T = 295 K. Final R = 0.035, wR = 0.042 for 1003 reflections with I greater than 3 sigma(I). The compound is an ammonium hydrogen oxalate. Both O atoms of the ionized carboxyl group act as acceptors in the formation of two hydrogen bonds: (a) an N--H...O bond linking the cation and anion with N...O and H...O distances of 2.722 (4) and 1.78 (5) A and (b) a strong O--H...O bond linking a chain of oxalate ions along a with O...O and H...O distances of 2.578 (4) and 1.59 (6) A. The relative stereochemistry of the heterocyclic and aromatic rings in the cation is similar to that in morphine.

Structure of 5-hydroxy-5-phenyl-7-azatricyclo[7.4.0.02,7]trideca-2,9(1), 10,12-tetraen-8-one by the consistent electron density approach.

C18H15NO2, Mr = 277.3, monoclinic, P21/n, a = 7.408 (2), b = 22.311 (7), c = 8.613 (2) A, beta = 103.53 (3) degrees, V = 1384 (1) A3, Z = 4, Dx = 1.33 g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 0.94 cm-1, F(000) = 594, T = 293 K, 2229 unique diffractometer data, 963 with I greater than 3 sigma(I), R = 0.050. Structure solution was by the consistent electron density approach which combines the concepts of the OMIT map and density modification procedures. The benzolactam portion of the molecule is highly planar; most bond lengths and angles have typical values.

Synthesis and pharmacological activity of 6-aryl-2-azabicyclo[4.2.1]nonanes.

A series of 6-phenyl-, 6-(m-methoxyphenyl)-, and 6-(m-hydroxyphenyl)-2-azabicyclo[4.2.1]nonanes was synthesized by a sequence involving alkylation of an appropriate 2-arylcyclopentanone with an aminoalkyl substituent. Subsequent ring closure at the other alpha position on the cyclopentanone ring and Wolff-Kishner reduction afforded the title compound. Several derivatives of these materials showed activity in an antinociceptive assay comparable to codeine. Most analogues were either inactive or toxic.

Synthesis and pharmacological properties of 1,2,3,4,5,6-hexahydro-1,6-methano-2-benzazocines.

1,2,3,4,5,6-Hexahydro-1,6-methano-2-benzazocine, 2'-methoxy-1,2,3,4,5,6-hexahydro-1,6-methano-2-benzazocine, and N-alkyl derivatives of 2'-hydroxy-1,2,3,4,5,6-hexahydro-1,6-methano-2-benzazocine have been synthesized in order to evaluate their analgesic activities. These compounds show only slight antinociceptive activities in the mouse hot-plate assay.

Synthesis and pharmacological activity of 2,3,4,5,-tetrahydro-1,5-methano-1H-3-benzazepines.

2,3,4,5-Tetrahydro-1,5-methano-1H-3benzazepine (4) has been synthesized from 2,3-dioxobenzonorbornene. Oxidative cleavage of the diketone to cis-1,3-indandicarboxylic acid, followed by closure to the corresponding amhydride, conversion to the imide, and lithium aluminum hydride reduction, gave 4. Compound 4 and its N-derivatives show no analgesic activity in the mouse hot-plate assay and little antagonist activity in a tail-flick assay.

Synthesis and analgetic activity of 1,2,3,4,5,6-hexahydro-1,6-methano-3-benzozocines.

1,2,3,4,5,6-Hexahydro-1,6-methano-3-benzazocine (1) has been synthesized via a four-step sequence from benzo-norbornadiene. This compound and its N-methyl derivative are more active than codeine in the mouse hot-plate antinociceptive assay and will not suppor morphine dependence in Rhesus monkeys.

Structural factors influencing the biodegradation of imides.

Comparative studies on the biodegradability of amides and imides are presented. Low-molecular-weight imides of varying chain lengths (4, 6, 7, 8, 18, and 20 carbons) were biodegrable. N-alkyl substitution of amides and imides resulted in non-biodegrable derivatives when the amide portion was greater than two carbons in length. N-alkyl-substituted derivatives of acetamide or diacetamide, however, were biodegrable. Several soil isolates, including Aspergillus niger and species of Flavobacterium and Alcaligenes, were capable of growth with imides as sole N or C sources.

NMR-studies of triiodothyropropionic acid in ethanol-HCl.

The barrier to rotation in the N-acetyl methyl ester of the thyroxine was found to be 8.6 kcal mol-1. Previous experiments determining the barrier to rotation in triiodothyropropionic acid in HCl-ethanol were shown to be in error.

Sex pheromone of the queen butterfly: chemistry.

Two major components in the "hairpencil" secretion of the male of the queen butterfly (Danaus gilippus berenice) have been identified. One, a crystalline ketone (2,3-dihydro-7-methyl-1H-pyrrolizin-1-one), is known from another danaid butterfly. The other, a viscous terpenoid alcohol (trans, trans-3,7-dimethyldeca-2,6-dien-1,10-diol), is new; its structure is confirmed by an unambiguous synthesis.