A one-step synthesis of a deuterated paclitaxel analogue: 10-deacetoxy-(10alpha-2H)paclitaxel.

10-Deacetoxy-(10alpha-2H)paclitaxel was prepared in one step via the samarium diiodide mediated deoxygenation of paclitaxel in the presence of D2O.

The scarlet letter: Reichstein's Substance S. A comparison of the angiostatic properties of 5 alpha-tetrahydro S and 5 beta-tetrahydro S.

5 beta-Tetrahydro-Reichstein's Substance S (3 alpha, 5 beta-THS) from different sources yielded variable bioassay activity in the chick chorio-allantoic membrane assay system. Physical characterization showed impure products. Synthesis of this compound by two different routes yielded active and inactive 3 alpha, 5 beta-THS.

Inhibition of angiogenesis by suramin.

In this study, we have determined the ability of suramin to inhibit angiogenesis in the chick chorioallantoic membrane. Suramin alone showed significant angiostatic activity in a dose-related manner. Suramin also potentiated the activity of the angiostatic steroids, cortisol-21-phosphate, 17 alpha-hydroxyprogesterone, tetrahydrocortisol, and tetrahydrocortexolone.

Structure-function relationship of 3-phosphoglycerate analogues with platelet aggregation and thromboxane A2 formation.

We have studied the effects of 2,3-diphosphoglycerate (2,3-DPG), 3-phosphoglycerate (3-PG), 3-phosphoglyceraldehyde (3-PGA), 2-phosphoglycerate (2-PG) and beta-glycerol phosphate (beta-GP) on platelet aggregation and on thromboxane B2 (TXB2) formation. The results show that 2,3-DPG, 3-PG, and 3-PGA inhibited platelet aggregation and TXB2 formation induced by norepinephrine, ADP, epinephrine, and collagen; but they also induced platelet aggregation and TXB2 formation in the presence of subthreshold concentrations of Na arachidonate. 2-PG and beta-GP were inactive.

The combined effects of 2,3-DPG and Na-arachidonate on platelet aggregation and on TXA2 formation.

We have investigated the effects of 2,3-DPG on platelet aggregation in the presence of suboptimal concentrations of Na-Arachidonate by using the two cuvette transfer experiments of Hamberg, Svensson and Samuelsson (3). The results show that 2,3-DPG enhanced or induced platelet aggregation in the presence of suboptimal concentrations of Na-Arachidonate. Imidazole, a TXA2 synthetase inhibitor, and Lasix, when added inhibited 2,3-DPG effects on platelet aggregation, suggesting that 2,3-DPG may act either on cyclooxygenase or on TXA2 synthetase of prostaglandin synthesis.

Ethynylestradiol-17 beta D-ring glucuronide conjugates are potent cholestatic agents in the rat.

17 alpha-Ethynylestradiol-17 beta (beta-D-glucuronide) [EE217 beta (beta G)], a metabolite of 17 alpha-ethynylestradiol (EE2) identified in urine of women taking EE2 in oral contraceptives, and its synthetic anomer, 17 alpha-ethynylestradiol-17 beta (alpha-D-glucuronide), [EE217 beta (alpha G)], were administered intravenously to female rats in order to determine their effects on bile flow. Both agents induced an immediate, profound and dose-dependent decrease in bile flow which returned to control levels within 1-8 hr. The logarithm of the dose vs the cholestatic response curves for the two anomers were not parallel.

Synthesis and characterization of the anomeric pair of 17 beta-glucuronides of ethynylestradiol.

The alpha- and beta-anomers of the 17 beta-D-glucuronide conjugate of ethynylestradiol were synthesized by the SnCl4-promoted reaction between beta-acetoxy GAM and the t-17 beta-hydroxyl group of EE2-3-acetate. The conjugates were resolved by crystallization and HPLC. Positive identification was established by u.

Ethynyl cleavage of 17 alpha-ethynylestradiol in the rhesus monkey.

17 alpha-Ethynylestradiol (EE2)[20,21-14C] and [9,11-3H] were administered by intragastric intubation to three adult female rhesus monkeys. Quantification of the tritium isotope indicated that the peak plasma radioactivity (3.4-6.

A new and improved synthesis of 19-iodocholesterol 3-acetate.

19-Iodocholesterol 3-acetate (VI) was synthesized in a single step by iodo group substitution for hydroxyl using either one of two different reagents: (1) carbodiimidonium methiodide (VIII) or (2) triphenyl-phosphine/N-iodosuccinimide (IX). The yields were as satisfactory as those obtained from the two step iodide replacement of a 19-hydroxy group via the 19-tosyloxy group. The principal intermediate, 19-hydroxy cholesterol 3-acetate (V), was derived in appreciable quantities, and relatively inexpensively, through the Pb (OCOCH3) 4 photolytic oxidation of the bromohydrin of cholesterol 3-acetate (III) to the epoxide (IV) thence Zn reduction to the 19-hydroxy compound.

The use of tetrahydrocortisone-3-beta-D-glucuronide in the measurement of urinary 17-hydroxycorticosteroids.

THE 3-G was added to H2O and 56 urines, and the recovered THE was measured by the Porter-Silber method. The recovery from H2O was quantitative (98 +/- 2%), but highly variables from urine, ranging from 35 to 100%. The necessity of the proper standard in analysis of urinary steroid glucuronides was demonstrated.