The significance of histidines in "thyrotropin-releasing" hormone (TRH)

The syntheses and biological activities of 4 analogues of the thyrotropin-releasing hormone (TRH) are described. In these analogues the histidine residue has been replaced by L -lysine, L -α,γ-diaminobutyric acid, β-(3-pyrazolyl)-L -alanine, and L-arginine. All analogues exhibited the characteristic biological responses of TRH. For the β-(3-pyrazolyl)-L -alanine analogue as well as for TRH the bioassays suggest an induction of a strong and rapid resynthesis of thyrotropin (TSH) in higher (μg) concentrations.     

Synthesis of thyrotropin-releasing hormone-related peptides using N alpha-tert-butyloxycarbonyl-omega-(N-tert-butyloxycarbonylcarbamoyl)- alpha-amino acids

Application of N alpha,Nca-di-tert-butyloxycarbonylhomoglutamine to synthesis of thyrotropin-releasing hormone (TRH) analogs was examined. The delta-lactam formation from homoglutaminylpeptides took place more easily than gamma-lactam formation from glutaminylpeptides in water or dioxane containing acetic acid. [pHgu1,Nva2]-TRH had dose-dependent antagonistic activity against pentobarbital anesthesia in mice, but almost no binding activity to TRH receptor in rat brain.     

Cyclic peptides of sarcosine. Syntheses and conformation.

A series of cyclic peptides of sarcosine with the general formula c-Sar-n, n=2-8, has been synthesized and conformational studies carried out both in solution and in the solid. The rings are conformationally very homogeneous and contain both cis and trans amide bonds. Their barriers to ring inversion are high; in the smaller rings this is attributed to steric hindrance, caused by the N-methyl-groups, whilst in the larger rings the folding of the chain in helical segments plays an important role.     

Syntheses and photophysical properties of some 5(2)-aryl-2(5)-(4-pyridyl)oxazoles and related oxadiazoles and furans

A number of 5-aryl-2-(4-pyridyl)oxazoles, a 2-aryl-5-(4-pyridyl)oxazole, the related oxadiazole and furan, several 2-(4-pyridyl)cycloalkano[d]oxazoles, and many of their quaternary salts were prepared. No single standard synthesis was effective for preparation of more than a few of the 25 free bases described; methods often unique to a base were employed. Minor variations in structure sometimes produced large differences in absorption and emission wavelengths, as well as in the magnitude of the extinction coefficient. The salts are of interest as laser dyes, scintillation fluors, biological stains, and shifters for luminescent solar concentrators.     

Syntheses of (±)-pyrenophorin and (±)-colletallol

Pyrenophorin $\text{1}$ and colletallol $\text{3}$ were synthesized in their racemic forms from the corresponding hydroxycarboxylic acids $\text{9}$ and $\text{14}$ via stereoselective formation of the requisite trans double bonds after macrocyclization.     

Syntheses and properties of related polyoxadiazoles and polytriazoles

New aromatic poly-1,2,4-triazoles and poly-1,3,4-oxadiazoles are studied as thermally stable membrane materials. Various groups were introduced onto the pendant phenyl groups of poly-1,2,4-triazoles. Glass transition temperature, degradation temperature, and cold crystallization behavior were studied as a function of these groups. Cold crystallization appeared to be highly sensitive to macromolecular regularity. The solubility of poly-1,3,4-oxadiazoles was highly improved upon incorporation of 5-t-butylisophthalic, 1,1,3-trimethyl-3-phenylindane, 4,4′-(2,2′-diphenyl) hexafluoro propane, and diphenyl ether groups into the polymeric main chain, whereas the high glass transition temperatures and degradation temperatures typical for aromatic poly-1,3,4-oxadiazoles were maintained. © 1994 John Wiley & Sons, Inc.     

Syntheses of a stable tristibine and of related antimony compounds with the 2,6-dimesitylphenyl (Dmp) substituent

DmpSbBr₂ (Dmp = 2,6-Mes₂C₆H₃) (1) is obtained by the reaction of DmpMgBr with SbCl₃. The reaction of 1 with KI in ethanol gives DmpSbI₂ (2). Dmp(Ph)SbBr (3) is prepared from DmpMgBr and PhSbCl₂. Compound 1 or 3 react with LiAlH₄ to form DmpSbH₂ (4) or Dmp(Ph)SbH (5). Compound 4 reacts with MeI in presence of DBU to give Dmp(Me)SbH (6). DmpSb(SbMe₂)₂ (7) is obtained from 4 and Me₄Sb₂. Elimination of hydrogen from 6 gives [Dmp(Me)Sb]₂ (8). Hydrolysis of 3 gives Dmp(Ph)SbOH (9). The molecular structures of 1-3, 5, 8 and 9 were determined by X-ray diffraction on single crystals.     

Syntheses of vinca alkaloids and related compounds. 104. A concise synthesis of (-)-vincapusine

beta-Iodo-enamines with an eburnane skeleton (5a and 5c) were obtained with the aid of iodine from compounds 2a and 2c and were then transformed into hydroxyl lactams (6a and 6c) with CuSO4.5H2O in a mixture of DMF and water. Lactams (6a and 6c) were reduced selectively with BH3.SMe2 to result in the first synthesis of (-)-vincapusine (4a) as well as its natural 14-decarbomethoxy analogue (4c).     

Syntheses of polycyclic-1,4-dithiines and related heterocycles

Reactions of dihalogenoquinones or dihalogenoquinoxalines with thioamides gave the corresponding 1,4-dithiines in high yields. Many of polycyclic 1,4-dithiin derivatives can be synthesized by the reactions of dihalogenoheterocycles with thioamides, and they are useful as pigments and functional materials for electro-optical applications. Some of heteroaromatic-1,4-dithiins formed an intermolecular charge-transfer (CT) complex with a π-acceptor such as TCNQ, and they are useful as π-donors for CT complex.     

Total Syntheses of (-)-Papuamine and (-)-Haliclonadiamine

The pentacyclic marine alkaloids (-)-papuamine (1) and (-)-haliclonadiamine (2) have been prepared by total synthesis. The synthesis began with (-)-8, which was converted into diester 20 by way of bis-mesylate 17, dinitrile 18, and diacid 19. Dieckmann cyclization of 20 provided keto ester 21, which was transformed into acetal 22. After hydrolysis of the acetal, ketone 25 was subjected to reductive amination with 1,3-propanediamine and sodium triacetoxyborohydride to obtain diamines 26 and 27 as a 71:29 mixture of diastereomers, favoring the symmetrical isomer having the papuamine relative configuration. After transformation of the diamines to their t-Boc derivatives, the benzyl ethers were cleaved and the resulting diol was oxidized to dialdehyde 30. Application of the Seyferth procedure for conversion of aldehydes to alkynes gave a mixture of diynes 31 and 32. After removal of the t-Boc protecting groups from 31, diamino diyne 15 was treated with tributylstannane and azoisobutyronitrile to obtain the bis-vinylstannane 34. Treatment of this compound with Pd(II) and Cu(I) in the presence of air produced (-)-papuamine (1). (-)-Haliclonadiamine (2) was obtained from the unsymmetrical isomer, 32. The NMR spectra of the synthetic alkaloids were identical to those of authentic samples of the natural alkaloids.     

Syntheses of (-)-pelletierine and (-)-homopipecolic acid

Enantiomeric syntheses of (-)-homopipecolic acid and (-)-pelletierine have been achieved by chiral resolution of tropanol followed by Baeyer-Villiger oxidation. The methodology provides a practical route for the synthesis of optically pure piperidines.     

An efficient synthesis of thyrotropin releasing hormone (TRH)

A convenient and simple synthesis of L -pyroglutamyl-L -histidyl-L -prolinamide is described. Two pathways using the solid phase technique have led to the pure tripeptide.     

Synthesis of peptides related to immunoglobulin E (IgE) and the examination of their pharmacological activity

Five kinds of oligopeptides H-Asp-Ser-Asp-OH (1), H-Asp-Gly-Lys-OH (2), H-Ser-Asp-Gly-Lys-OH (3), H-Asp-Ser-Asp-Gly-Lys-OH (4), and H-Ala-Asp-Ser-Asp-Gly-Lys-OH (5) related to immunoglobulin E (IgE) were synthesized by the conventional solution method with the objective of obtaining a new type of antiallergic agent. Their pharmacological activity was examined by measuring the inhibition of the production of IgE and relaxation of the smooth muscle contraction of rabbit aorta. H-Ala-Asp-Ser-Asp-Gly-Lys-OH (5) displayed potent inhibition against the production of IgE antibody (69.6%) and relaxation against the contraction of rabbit aorta.     

Syntheses of bis(imino)thietans

The reactions of sulfonyliminothiirans ($\text{1}$) with isonitriles and those of ketenimines with arylsulfonyl isothiocyanates yield the title compounds $\text{2}$. In contrast, benzoyl isothiocyanate undergoes a Diels-Alder reaction with ketenimines to give 1,3,5-oxadiazine-4-thiones ($\text{3}$).