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Biomedical subjects

F Sarabia

Publications and source records attributed to F Sarabia.

9 recordsLinked to original sources
PubMed2002

Novel chemistry of alpha-tosyloxy ketones: applications to the solution- and solid-phase synthesis of privileged heterocycle and enediyne libraries.

New synthetic technologies for the preparation and elaboration of alpha-tosyloxy ketones in solution- and on solid-phase are described. Both olefins and ketones serve as precursors to these relatively stable chemical entities: olefins via a novel one-pot epoxidation, arylsulfonic acid displacement, and oxidation sequence, and ketones by direct exposure to arylsulfonic acids in the presence of diacetoxy iodobenzene. Reaction of these substrates with O-, S-, or N-centered nucleophiles leads to incorporation of the nucleophile with concomitant expulsion of the sulfonate, while exposure to bis-functional nucleophiles furnishes annulated heterocyclic systems. In addition, the reactions of carbon-centered nucleophiles with alpha-tosylyloxy ketones are also explored. The collated data for all these nucleophiles provide compelling evidence for the proposal that different reaction pathways are followed when alpha-tosyloxy ketones are engaged by "hard" versus "soft" nucleophiles. The accessibility and site-selectivity of the chemistry demonstrated herein offer the promise of an expanded use for this moiety in solid-phase library construction, in particular, and in the field of organic synthesis, in general.

Alkynes↗
PubMed2001

Bone mass after long-term euthyroidism in former hyperthyroid women treated with (131)I influence of menopausal status.

The objective of this study was to assess bone mineral density (BMD) and bone markers in former hyperthyroid females after long-term euthyroidism (>4 yr) following (131)I therapy, as well as the potential influence of the timing of menopause. Twenty-six females ages 57 +/- 8 yr previously diagnosed with hyperthyroidism and treated with (131)I who were euthyroid for a minimum of the last 4 yr (10 +/- 5 yr) were studied. Eighteen patients (69%) were on levothyroxine (LT(4)) replacement therapy for 9 +/- 4 yr. BMD (g/cm(2) and Z-score) was measured by dual X-ray absorptiometry in the lumbar spine, femoral neck, and Ward's triangle. BMD (Z-score) was lower than the normal reference values for the Spanish population in all sites (lumbar spine: -0.65 +/- 1.13; femoral neck: -0.47 +/- 0.95; Ward's triangle: -0.37 +/- 0.88). No differences were found between BMD values according to the etiology of the hyperthyroidism or current LT(4) therapy. Current postmenopausal patients (n = 21) showed lower BMD than current premenopausal patients in the lumbar spine and femoral neck (p < 0.05). Those women who were postmenopausal at the time of the (131)I therapy (n = 15) also had lower lumbar spine BMD than premenopausal patients (p = 0.01), while no significant difference in BMD was seen according to the menopausal status when hyperthyroidism was diagnosed. Former hyperthyroid patients after long-term euthyroidism following (131)I therapy showed reduced BMD at the lumbar spine and proximal femur. Menopausal women showed a greater reduction in bone density. The menopausal status at the time of diagnosis did not seem to have long-term effects in bone density; nevertheless, an early therapeutic intervention in premenopause is suggested to reduce bone loss.

Absorptiometry, Photon↗
PubMed1999

Total synthesis of epothilone E and related side-chain modified analogues via a Stille coupling based strategy.

A Stille coupling strategy has been utilized to complete a total synthesis of epothilone E from vinyl iodide 7 and thiazole-stannane 8h. The central core fragment 7 and its trans-isomer 11 were prepared from triene 15 using ring-closing metathesis (RCM), and were subsequently coupled to a variety of alternative stannanes to provide a library of epothilone analogues 18a-o and 19a-o. The Stille coupling approach was then used to prepare epothilone B analogues from the key macrolactone intermediate 24 which was itself synthesized by a macrolactonization based strategy.

Chromatography, Thin Layer↗
PubMed1998

Synthesis and biological properties of C12,13-cyclopropyl-epothilone A and related epothilones.

BACKGROUND: The epothilones are natural substances that are potently cytotoxic, having an almost identical mode of action to Taxoltrade mark as tubulin-polymerization and microtubule-stabilizing agents. The development of detailed structure-activity relationships for these compounds and the further elucidation of their mechanism of action is of high priority. RESULTS: The chemical synthesis of the C12,13-cyclopropyl analog of epothilone A and its C12,13-trans-diastereoisomer has been accomplished. These compounds and several other epothilone analogs have been screened for their ability to induce tubulin polymerization and death of a number of tumor cells. Several interesting structure-activity trends within this family of compounds were identified. CONCLUSIONS: The results of the biological tests conducted in this study have demonstrated that, although a number of positions on the epothilone skeleton are amenable to modification without significant loss of biological activity, the replacement of the epoxide moiety of epothilone A with a cyclopropyl group leads to total loss of activity.

Animals↗
PubMed1997

Synthesis of epothilones A and B in solid and solution phase.

Epothilones A and B, two compounds that have been recently isolated from myxobacterium Sorangium cellulosum strain 90, have generated intense interest among chemists, biologists and clinicians owing to the structural complexity, unusual mechanism of interaction with microtubules and anticancer potential of these molecules. Like taxol, they exhibit cytotoxicity against tumour cells by inducing microtubule assembly and stabilization, even in taxol-resistant cell lines. Following the structural elucidation of these molecules by X-ray crystallography in 1996, several syntheses of epothilones A and B have been reported, indicative of the potential importance of these molecules in the cancer field. Here we report the first solid-phase synthesis of epothilone A, the total synthesis of epothilone B, and the generation of a small epothilone library. The solid-phase synthesis applied here to epothilone A could open up new possibilities in natural-product synthesis and, together with solution-phase synthesis of other epothilones, paves the way for the generation of large combinatorial libraries of these important molecules for biological screening.

Antineoplastic Agents↗
PubMed1990

[Serum osteocalcin and bone turnover in hyperthyroidism].

In hyperthyroidism an increased bone turnover may appear, essentially due to a higher bone resorption. In order to evaluate this complication we have measured the serum levels of Osteocalcin (BGP) in 41 patients, mean age 43 +/- 18 (+/- SD) years. BGP is a protein synthesized by osteoblasts which may be employed as an specific and non-aggressive marker of bone turnover. Serum BGP was significantly increased in these patients with respect to normals (6.2 +/- 4.2 vs 3.7 +/- 1.3 ng/ml). The total group was divided according to BGP values higher and lower than 3.7 ng/ml, emerging two groups with BGP 7.9 +/- 3.8 (n = 30) y 2.2 +/- 1.2 ng/ml (n = 11), respectively. There were not differences between these two groups regarding to thyroid hormones or other data of mineral metabolism. In the total group, only serum BGP and T3 were correlated. Our results suggest the existence of a double effect of hyperthyroidism on bone, as well as a temporal dissociation between thyroid synthesis and bone metabolism.

Adult↗
PubMed1980

Computerized tomographic evidence of cerebral atrophy in heavy drinkers.

Of 50 heavy drinkers referred for nonalcoholic psychiatric problems, 56% had computerized tomographic evidence of cerebral atrophy. This contrasted with a rate of 6% in patients with schizophrenia and affective illnesses who had taken psychotropic drugs for at least ten years. Further, the severity of atrophy was greater in the group of heavy drinkers. The results support a role for computerized tomography in assessment of patients with chronic alcoholic problems.

Adult↗