Human calcitonin. Structure of calcitonin M and D

Human calcitonin M and its dimer calcitonin D, two highly active peptides isolated from C cell tumours, were subjected to sequence studies using chemical and enzymatic methods. For calcitonin M, containing 32 amino acid residues, the following structure was derived: Though the disulphide bridge between position 1 and 7, and the C-terminal proline amide of human calcitonin M are the same as in porcine α-thyrocalcitonin, many amino acid residues - 18 in all - are different throughout the molecule. Arginine and tryptophan are absent; on the other hand, lysine and isoleucine are to be found at position 18 and 27 respectively. Methionine changes its place from position 25 to 8 adjacent to the disulphide bridge. Experimental evidence indicates that calcitonin D represents the antiparallel dimeer of calcitonin M.     

Human calcitonin. V. Synthesis and characterization of the protected calcitonin M-(1-10)-decapeptide

The present report describes in detail the synthesis and characterisation of the protected Calcitonin M decapeptide 1–10, , a key intermediate in the synthesis of Calcitonin M. I. was obtained from the openchain precursor Boc-Cys (Trt)-Gly-Asn-Leu-Ser (But)-Thr (But)-Cys (Trt)-Met-Leu-Gly-OH (II) by oxidation with iodine in a yield of 70%, after purification by counter-current distribution. II was prepared by fragment coupling of the sequences 1–4 and 5–10. The free calcitonin M (1–10)-decapeptide, obtained from I by removal of the protecting groups by acidolysis, has no hypocalcaemic activity and does not inhibit specific binding of calcitonin M to its antibodies in rabbit serum.     

Human calcitonin. I. Isolation and characterization

Two highly active calcitonin peptides, M with 32 amino acids, and D a dimer of M, were isolated from a large human mediastinal C cell tumour. D can easily be transformed into M by the action of 1N ammonia; D and M afford two different sulphoxides, but all four peptides yield the same product upon oxidation with performic acid. Both D and M have a potency of about 120 MRC units/mg dry weight; their sulphoxides, by contrast, are almost inactive. Tryptic digestion of M produces an N-terminal octadecapeptide (Tr_I) and a C-terminal tetradecapeptide (Tr_II), the latter being also obtained from D. Amino acid analysis and other analytical data are presented. The structure of the human calcitonin peptides D and M is thus very different from that of porcine α-thyrocalcitonin.     

Fluoro-containing Heterocycles. IV. Synthesis of Benzimidazole Derivatives

2-Mercapto-5,6-difluorobenzimidazole reacts with aliphatic and alicyclic ketones in acetic acid in the presence of catalytic amount of sulfuric acid to afford fluorinated derivatives of 2,3-disubstituted benz[4,5]imidazo[2,1-b][1,3]thiazoles. Reaction with aromatic -haloketones occurs in another way: to furnish 2-phenylacylthio-5,6-difluorobenzimidazoles that in the system acetic anhydride-pyridine undergo cyclization into the corresponding fluorinated derivatives of benz[4,5]imidazo[2,1-b][1,3]thiazoles.     

Polyarylates. IV. Synthesis of block copolymers via two-step interfacial polycondensation

A new method for preparing block copolyarylates via two-step interfacial polycondensation is proposed. First, oligomers with acid chloride end groups were obtained from interfacial polycondensation with a mole ratio of bisphenol A to diacid chloride(s) less than I. In the second step, two reaction systems containing various oligomers were mixed thoroughly and more bisphenolate was charged into this mixture. The synthesis of the block copolyarylates was justified from the viewpoint of statistics, and of differences in molecular weight between oligomers and block copolymers. These block copolyarylates could be differentiated from polyarylates through crystal-line behavior and solubility in m-cresol analyses.     

Synthesis based on β-phenylethylamines. IV. Synthesis and antiarrhythmic activity of substituted phenylalkylamines and N-benzyltetrahydroisoquinolines

A number of N-benzyltetrahydroisoquinolines forming analogues of sendaverine have been synthesized. Results on the pharmacological activity of the compounds synthesized are presented. Institute of Chemistry of Plant Substances, Academy of Sciences of the Uzbekistan Republic, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 404–409, May–June, 1993.     

Studies on Agarofurans IV. The Synthesis of 4-Substitutioned Agarofurans

A new synthetic route for α-agarofuran(1b) is described. Several agarofuran derivatives were synthesized in similar way. Derivative 1d was also synthesized in a novel way, in which the substitution at C-4 was performed quantitatively. An ideal condition for cyclization of diol 7 to agarofuran (1) was found.     

Synthesis of Isodehydroilludin M

Isodehydroilludin M was synthesized from carbonyl ylid 1,3-dipolar cycloaddition product that was further elaborated with an unusual PCC-mediated double oxidation reaction.     

Synthesis of oxirnes. IV. 2-pyridinealdoxime methiodides from 2-picoline methiodides

The Ortoleva-King-Krohnke sequence was used to prepare substituted 2-pyridinealdoxime methiodides. The methodology was extended to prepare three analogs in which two molecules of 5-hydroxy-2-pyridinealdoxime methiodide were coupled through the 5-position with dihalides.     

Fused 1,2-dithioles. IV. Synthesis and reactions of 1,2-dithiole s-oxides

1,2-Dithiolopyrrolones and their heterologues of type 1 are resonance stabilized systems displaying a high dipole moment. Upon oxidation with organic peracids compounds 2 , 5 , 15a, 16a, 20a and 25a gave the corresponding S(2)-oxides and, depending on substituents, in some cases the S(2)- and S(1)-dioxides. The S(2)-monoxides showed a proclivity to disproportionation and were easily reduced to dithioles with symme trical dimethylhydrazine. From S(2)-oxides and several primary amines bicyclic isothiazole-S-oxides were obtained (S/N-exchange reaction). From the N-unsubstituted isothiazole S-oxide 10e the N-hydroxyisothiazole 9d was synthesized by an aza-Pummerer-type rearrangement. The assumption is made that S(2)-oxides may be biologically important as active metabolites of pyrrothines and analogues of type 1 in their action as antibacterials and antimycobacterials.     

Napthyridines. IV. Synthesis of benzo[f]-1,7-naphthyridines

Benzo[f]-1,7-naphthyridines have been synthesized from 3-nitrolepidine ( 3 ) by a sequence involving monobromination of the methyl group of 3 , oxidation of the bromomethyl group to the carboxyladehyde group by Franzen's trimethylamine N-oxide procedure, and conversion of the resultant 3-nitro-1-quinoline-carboxaldehyde ( 6 ) to the benzo[f]-1,7-naphthyridine by the Borsche modification of the Friedlander cyclization.