Hydroxymethyl Side Chain Research Articles

Serine and d‐serine position‐1 substituted angiotensin II analogues Synthesis using new 2,3,5,6‐tetrafluorophenyl active esters and biological activities

[Ser1]- (32), [D-Ser1]-(29), [Ser1, Leu8]-(31), and [D-Ser1, Leu8] angiotensin II (30) were synthesized by a repetitive method in solution using new protected amino acid 2,3,5,6- tetrafluorophenyl active esters. 32 and 29 were agonists, and 31 and 30 were specific antagonists to angiotensin II (AII) receptors determined by the rabbit aortic strip (RAS) and rat blood pressure (RBP) assays. It was found that the hydroxymethyl side chains of serine and D-serine in position-1 has an important influence on the agonistic activity of the analogues. The pressor activities of 32 and 29 were 129 and 314%, respectively, as potent as AII. On the other hand, 31 and 30 were effective in antagonizing the AII-induced contraction of RAS and rise in RBP.

An application of polyalcohols prepared from diols. I. Elastic polymers with functional groups prepared by chemical modifications

An elastic polymer with hydroxymethyl side chains, which contains some crosslinked structure, has been prepared by treating its prepolymer with maleic anhydride and styrene in the presence of an initiator. Its mechanical properties were varied largely by the molar ratio of the hydroxyl group:maleic anhydride:styrene. A typical example of the polymer showed elongation 69%, tensile strength 0.85 kgf/mm2, and Young's modulus 9.4 kgf/mm2. Some other modifications are also examined.

Novel polyalcohols with hydroxymethyl side chains from base-catalyzed polycondensation of diols

Reaction en presence de phenylate de potassium ou d'oxyde de naphtyl-2 potassium. Le decanediol-1,10 donne un polymere soluble meme dans la pyridine et le methanol

Studies of peptide antibiotics

Gramicidin S (GS) analogs, [D-Ser4,4']-GS and its precursor [O-benzyl-D-Ser4,4']-GS, were synthesized by the conventional method in order to evaluate the role of the hydroxymethyl side chains in D-Ser at 4,4' positions on the biological activity. Another analog [L-Orn(delta-Boc)2,2',delta Ala4,D-Ser4']-GS was prepared from [D-Ser4,4']-GS by t-butyloxycarbonylation and successive dehydration using dicyclohexylcarbodiimide-CuCl as dehydrating reagent. The delta Ala residue was asymmetrically hydrogenated to D-Ala in the presence of Pd-black. On the microbial assays, [O-benzyl-D-Ser4,4']-GS showed high antimicrobial activity as natural GS, but [D-Ser4,4']-GS showed low activity; the structure-activity relationships of the analogs were discussed.

Dehydration of nigeran crystals: Crystal structure and morphological aspects

The crystal structure of anhydrous nigeran, poly[(1 → 3)-α- d-maltose], obtained from Penicillium crustosum has been determined by a combined electron diffraction. X-ray diffraction and packing analysis. The electron diffraction pattern from solution-grown single crystals shows some (h k I) reflections in the baseplane pattern. The polymer crystallizes with two chains passing through the cell of dimensions: a = 17.76, b = 6.0 and c = 14.62 A ̊ (fiber repeat). The space group is P2 12 12 1. The glycosidic torsion angles of this poly(disaccharide) were determined using an iteration process. The results are analyzed on the basis of the effect of side-group orientations on backbone conformation, and are compared with those obtained from a survey of relevant linear and cyclic oligosaccharides.The crystallographic reliability index was R e = 0.25 and R x = 0.30 when the model was tested against electron and X-ray diffraction data, respectively. The poly(disaccharide) chain is a 2-fold helix stabilized by an intrachain hydrogen bond between contiguous α-(1 → 4) residues. The hydroxymethyl side-chains are in the gauche-gauche form. Two such chains pack with anti-parallel polarity and the 2-fold screw axis coincides with the macromolecular axis. A network of hydrogen bonds holds the chains together in the crystal. In the condensed state, the nigeran chains are more or less extended depending on the state of hydration. The two extremes correspond to the “dry” and “wet” crystal forms. The transition between the two conformations takes place reversibly in the crystalline state. This is observed on solution-grown crystals, as well as in vivo where nigeran is found to occur in crystalline domains. Such a transition is analyzed in terms of the conformational flexibility of the backbone and in terms of the affine deformation concept. Morphological and textural transformations occurring as a result of drying are suggested to have important consequences on the subsequent microbiology such as enzymic digestion.

Metabolism of 3-(hydroxymethyl)-8-methoxychromone in the rat. I. Absorption, tissue distribution and excretion.

1. Two 14C-labelled preparations of 3-(hydroxymethyl)-8-methoxychromone were used to study the absorption, tissue distribution and excretion of isotope after oral administration to rats (20 mg/kg). 2. 14C, presumably from the labelled hydroxymethyl side-chain, was eliminated extensively as 14CO2. This excretion was triphasic; kinetic constants were calculated for each phase. 3. The major excretion route was via the kidney although significant quantities of isotope were excreted with the faeces. Isotope did not accumulate in tissues.

The structure of chitin

A new structure is proposed for the polysaccharide chitin, [C 8H 13O 5N] n. X-ray diffraction fibre photographs of lobster tendon reveal a well-defined orthorhombic lattice with the space group P2 12 12 1 and cell dimensions of a = 4.69 A ̊ , b = 19.13 A ̊ , and c = 10.43 A ̊ (fibre repeat). It is suggested that the unit cell contains two polysaccharide chains running in opposite directions and four asymmetric N-acetyl-glucosamine units which gives a density in close agreement with the observed experimental value of 1.42 g/ml. The structure was arrived at by a trial and error method, with the aid of an optical diffractometer for testing the diffraction patterns of the various possibilities suggested by stereochemical considerations. The structure finally arrived at, is in good agreement with infra-red absorption data, and has no short contacts. The chains are separated by a distance of 4.69 Å perpendicular to the “plane” of the sugar rings and consequently the NH and CO groups in the neighbouring aminoacetyl side chains are hydrogen bonded, the plane of the amide groups in the “trans” configuration being almost perpendicular to the fibre axis. The hydroxymethyl side chains containing a hydroxyl group are also hydrogen bonded, the OH of one being linked to the oxygen of a similar group from a neighbouring chain running in the opposite direction. The short hydroxyl group is intrahydrogen bonded to the oxygen of the amide group in the same asymmetric unit. The calculated intensities for the proposed set of coordinates are in fairly good agreement with observed X-ray intensities visually estimated from fibre photographs.