Julio D. Martín

Tachykinins and tachykinin receptors in human uterus

Studies were undertaken to determine the nature of the receptors mediating contractile effects of tachykinins in the uteri of nonpregnant women, and to analyse the expression of preprotachykinins (PPT), tachykinin receptors and the cell‐surface peptidase, neprilysin (NEP), in the myometrium from pregnant and nonpregnant women. The neurokinin B (NKB) precursor PPT‐B was expressed in higher levels in the myometrium from nonpregnant than from pregnant women. Faint expression of PPT‐A mRNA was detectable in the myometrium from nonpregnant but not pregnant women. PPT‐C, the gene encoding the novel tachykinin peptide hemokinin‐1 (HK‐1), was present in trace amounts in the uteri from both pregnant and nonpregnant women. Tachykinin NK2 receptors were more strongly expressed in tissues from nonpregnant than from pregnant women. NK1 receptor mRNA was present in low levels in tissues from both pregnant and nonpregnant women. A low abundance transcript corresponding to the NK3 receptor was present only in tissues from nonpregnant women. The mRNA expression of the tachykinin‐degrading enzyme NEP was lower in tissues from nonpregnant than from pregnant women. Substance P (SP), neurokinin A (NKA) and NKB, in the presence of the peptidase inhibitors thiorphan, captopril and bestatin, produced contractions of myometrium from nonpregnant women. The order of potency was NKA≫SP≥NKB. The potency of NKA was unchanged in the absence of peptidase inhibitors. The tachykinin NK2 receptor‐selective agonist [Lys5MeLeu9Nle10]NKA(4–l0) was approximately equipotent with NKA, but the tachykinin NK1 and NK3 receptor‐selective agonists [Sar9Met(O2)11]SP and [MePhe7]NKB were ineffective in the myometrium from nonpregnant women. The uterotonic effects of [Lys5MeLeu9Nle10]NKA(4–10) were antagonized by the tachykinin NK2 receptor‐selective antagonist SR48968. Neither atropine, nor phentolamine nor tetrodotoxin affected responses to [Lys5MeLeu9Nle10]NKA(4–10). These data are consistent with a role of tachykinins in the regulation of human uterine function, and reinforce the importance of NK2 receptors in the regulation of myometrial contraction.

Application of the Grubbs Ring-Closure Olefin Metathesis in the Synthesis of Trans-Fused Oxacycles

Abstract A highly efficient and flexible route to trans-fused oxacycles is outlined, which is based on the formation of seven-, eight-, and nine-membered oxacycles by ring-closing metathesis (RCM) as the key step.

A concise synthesis of ortho-condensed oxane-oxene, oxepene, oxocene and oxonene ring systems

Abstract An efficient strategy for the synthesis of trans -fused oxabicyclic systems involving thioannulation followed by a Ramberg-Backlund olefination as the key step is described.

Synthesis and biological studies of flexible brevetoxin/ciguatoxin models with marked conformational preference

Abstract A comparison of the more active polyether toxins which are selective activators of voltage-sensitive sodium channels (VSSC), indicate that these molecules are mostly flat, with a hinge part around the middle of the molecules and a large curvature at one of the ends. Assuming that the receptor is topographically complementary to the active molecules, from the result reported here we could conclude, that the specific requirements of the receptor region can be achieved by synthetic polyether models based on exclusive participation of oxane/oxepane moieties. A new convergent approach to give oxepene rings via double reduction of methyl diacetals is explored. In searching for biological models to further characterize Na+ channels, our studies show that different voltage-dependent Na+ channels are expressed in the rat uterus and activated by brevetoxin-B. However, selected compound models synthesized in this work, failed to inhibit or activate Na+ channel function.

Structure and absolute configurations of Dictyota sp. diterpenes

Eight diterpenes belonging to the dolostane carbon skeleton have been isolated from the Canary Island brown alga Dictyola sp. The structures including absolute configuration of these diterpenes were secured by X-ray analysis of the triol derivative 7 followed by chemical interconversions.

Ortho-Condensed oxane/polyoxygenated macrorings by ruthenium-catalyzed ring closing metathesis

Abstract A highly efficient and flexible route to trans -fused oxane/macrocyclic polyethers is outlined, which is based on the formation of 15-, 18-, and 21-membered oxacycles by ring-closing metathesis (RCM) as the key step.

Two new polyhalogenated monoterpenes from the red alga Plocamium cartilagineum

Abstract The structures and absolute configurations of two new halogenated alicyclic monoterpenes isolated from the ether extract of the red alga Plocamium cartilagineum (Linn) Dixon were determined as: 1 R ,2 S ,4 S ,5 R -5-chloro-2- E -chlorovinyl-1,4-dibromo-1,5-dimethylcyclohexane and 1 S ,2 S ,4 R ,5 S -2-bromo-1- E -bromovinyl-4,5-dichloro-1,5-dimethylcyclohexane, respectively.

A facile synthesis of an oxatricyclic trans-syn-trans-substituted oxepanyl framework

Abstract The regio- and stereochemistry of iodine-promoted transannular ring expansion of cyclic trans -1,2-epoxy-5(E)-ene systems is used to synthesise trans , syn , trans -substituted oxepanyl subunits.

Marine natural products of the Atlantic zone. Part VI. Base-catalysed rearrangement of taondiol

The base-catalysed isomerisation of taondiol (1; R1= R2= H), an aromatic terpenoid containing the 1H-naphtho[2,1-a]xanthen skeleton recently isolated from the marine alga Taonia atomaria(Dyctiotaceae), into its C-6a methyl epimer (2) has been studied. A free-radical mechanism is proposed for the reaction. Base-catalysed methyl inversion at C-6a was also carried out on 2-deoxy-9,11-dimethyltaondiol (21; R = H), prepared by condensation of (13R)-labda-8(20),14-dien-13-ol (18) with trimethylhydroquinone (19) and subsequent cyclisation.

Structure of 6-chloro-10-oxabicyclo[5.2.1]decane-2,3-diol

C 9 H 15 ClO 3 cristallise dans P2 1 /a avec a=11,627, b=7,486, c=11,625A, β=109,5°, Z=4 ; affinement jusqua R=0,074. La structure cristalline est stabilisee par des liaisons hydrogene intermoleculaires extensives, avec une interaction specifique entre le groupement hydroxyle (O3H) dune molecule et le groupement (O2H) hydroxyle de lautre, formant des chaines de liaisons hydrogene le long de laxe b