Mechanisms of inhibition of aldehyde dehydrogenase by nitroxyl, the active metabolite of the alcohol deterrent agent cyanamide

Nitroxyl, produced in the bioactivation of the alcohol deterrent agent cyanamide, is a potent inhibitor of aldehyde dehydrogenase (AIDH); however, the mechanism of inhibition of AlDH by nitroxyl has not been described previously. Nitroxyl is also generated from Angeli's salt (Na2N2O3) at physiological pH, and, indeed, Angeli's salt inhibited yeast AlDH in a time- and concentration-dependent manner, with IC50 values under anaerobic conditions with and without NAD+ of 1.3 and 1.8 microM, respectively. Benzaldehyde, a substrate for AlDH, competitively blocked the inhibition of this enzyme by nitroxyl in the presence of NAD+, but not in its absence, in accord with the ordered mechanism of this reaction. The sulfhydryl reagents dithiothreitol (5 mM) and reduced glutathione (10 mM) completely blocked the inhibition of AlDH by Angeli's salt. These thiols were also able to partially restore activity to the nitroxyl-inhibited enzyme, the extent of reactivation being dependent on the pH at which the inactivation occurred. This pH dependency indicates the formation of two inhibited forms of the enzyme, with an irreversible form predominant at pH 7.5 and below, and a reversible form predominant at pH 8.5 and above. The reversible form of the inhibited enzyme is postulated to be an intra-subunit disulfide, while the irreversible form is postulated to be a sulfinamide. Both forms of the inhibited enzyme are derived via a common N-hydroxysulfenamide intermediate produced by the addition of nitroxyl to active site cysteine thiol(s).     

Substitution effect of purine nucleosides on diisobutylaluminum hybride reduction

It is reported that the diisobutylaluminum hydride (DIBALH) reduction of inosine and adenosine derivatives (1a and 1d) causes cleavage of the ribose moiety to give the corresponding 9-ribitylhypoxanthine (2a) and 9-ribityladenine (2d), respectively. The substitution effect of purine nucleosides on the reduction was investigated. O6-alkylinosine derivatives (1b and 1c) were reduced in good yields like 1a. Introduction of methyl group into the N6-position of adenosine (1d), however, greatly reduced the reactivity toward DIBALH. The reduction of 7-deazainosine (3a) and 7-deazaadenosine (3b) hardly proceeded. These results suggest that oxygenophilicity of aluminum atom facilitates coordination of DIBALH to the 7-ring nitrogen atom and accelerate a cleavage of the ribose.     

Forskolin derivatives. I. Synthesis, and cardiovascular and adenylate cyclase-stimulating activities of water-soluble forskolins

Water-soluble forskolin and 7-deacetylforskolin derivatives with an aminoacetyl, a 3-aminopropionyl, or a 4-aminobutyryl group at the 6- or 7-position were prepared, and their positive inotropic as well as vasodilative activities were evaluated in anesthetized dogs. 7-Deacetylforskolin (2) and 7-deacetyl-1-silylforskolin (6) were converted to the corresponding 7-chloroacylderivatives (3, 7, 10), which were reacted with amines to obtain 7-aminoacyl-7-deacetylforskolins (4a-f, 9a, b, 11). The 7-acyl substituents migrated to the 6-position with sodium hydroxide in acetonitrile-water to afford 6-aminoacyl-7-deacetylforskolins (12a-f). The 7-position of 12a, d-f was selectively acetylated with acetyl chloride to obtain the corresponding 6-aminoacylforskolins (13a-d). Among the 6-aminoacylforskolins, 6-(3-dimethylaminopropionyl)forskolin (13b) and 6-(4-dimethylaminobutyryl)forskolin (13d) exhibited potent positive inotropic and vasodilative activities comparable to those of forskolin (1). The activities of 13b and 13d were approximately ten times more potent than those of 7-aminoacyl- and 6-aminoacyl-7-deacetylforskolins (4a-f, 9a, 12a-c, f). 6-Dimethylaminoacetylforskolin (13a) and 6-(3-diethylaminopropionyl)forskolin (13c) were less potent than 1. The effects of the soluble forskolins on adenylate cyclase activity were also examined in vitro. 6-Aminoacylforskolins (13a-d) exhibited potent adenylate cyclase-stimulating activity, comparable to that of 1.     

Inhibition of in vitro lipid peroxidation by stable steroidic nitroxyl radicals

4',4'-dimethylspiro (5 alpha-cholestane-3,2'-oxazolidin)-3'-yloxy (IK-1) and 7 alpha,12 alpha-dihydroxy-4',-4'-dimethylspiro (5 beta-cholan-24-oic-3,2'-oxazolidin)-3'-yloxy acid (IK-2), two stable steroidic nitroxyl radicals, were newly synthesized and tested as possible inhibitors of lipid peroxidation, induced by Fenton's reagent in both rat liver microsomes and egg phosphatidylcholine liposomes. The inhibitory activity, evaluated through the formation of thiobarbituric acid reactive substances (TBARS) and the conjugated diene, was compared with that of alpha-tocopherol and 2,2,6,6-tetramethylpiperidine-1-yloxy (TEMPO). In each model system IK-1 and IK-2 exhibited an IC50 of 8 microM and reduced the formation of TBARS and conjugated diene, showing IK-1 a potency comparable to alpha-tocopherol and higher than TEMPO. Moreover IK-1 and, to a lesser extent IK-2, reduced the lipid peroxidation induced in the microsomes by the water-soluble azo-initiator 2,2'-Azobis (2-methylpropionamidine) dihydrochloride (AMPH), indicating the IK-1 and IK-2 ability as chain-breaking antioxidants. The hydroxylamine 4',4'-dimethylspiro (5 alpha-cholestane-3,2'-oxazolidin)-3'-hydroxide (IK-3), obtained by chemical reduction of IK-1, was completely inactive as an inhibitor of lipid peroxidation in heat pre-treated microsomes and in liposomes. However in microsomes it was active since it was oxidized to the corresponding nitroxyl radical IK-1.     

The embryonic central nervous system lineages of Drosophila melanogaster. I. Neuroblast lineages derived from the ventral half of the neuroectoderm

Central nervous system development in Drosophila starts with the delamination from the neuroectoderm of about 30 neuroblasts (NBs) per hemisegment. Understanding the mechanisms leading to the specification of the individual NBs and their progeny requires the identification of their lineages. Here we describe 17 embryonic NB lineages derived from the ventral half of the neuroectoderm and we assign these lineages to identified medial and intermediate NBs. The lineages are composed of interneurons (NB 1-2, NB 2-1, MP2, NB 4-1, NB 5-1, NB 5-3, NB 6-1, NB 6-2, and NB 7-2), interneurons and motoneurons (NB 3-1, NB 3-2, NB 4-2, NB 5-2, NB 7-1, and NB 7-3), or interneurons, motoneurons, and glial cells (NB 1-1 and NB 2-2). NB 1-1, NB 2-2, and NB 3-1 form segment-specific lineages. Neuroectodermal progenitors forming NB 2-1, NB 5-1, and NB 7-3 divide while still in the ectoderm to give rise to an additional epidermoblast. Expression of segmentation genes is not lineal in the clones of NB 1-2 and NB 7-3 (engrailed), NB 1-1, NB 4-2, and NB 7-1 (even-skipped), and NB 7-1 (gooseberry-proximal). The timing of delamination for individual NBs as well as the number of their progeny is not strictly invariant. The 17 NBs produce about 200 neurons and only three glial cells, corresponding to about 70% of the estimated total number of neurons and 10% of the glial cells per thoracic and abdominal hemisegment. Previously identified neural cell types were linked to particular lineages and we introduce a systematic terminology for the ventral nerve cord neurons. The wild-type clones provide a foundation for the analysis of mutants, expression patterns, and experimental manipulations.     

Neutrophil-specific antigen NB1 inhibits neutrophil-endothelial cell interactions

Neutrophil-specific antigen NB1 is located on a 58 to 64 kd glycosyl phosphatidylinositol-linked plasma membrane glycoprotein. NB1 antigen can be detected on neutrophils from 97% of healthy volunteers, and NB1 antigen is expressed on subpopulations of neutrophils. Neutrophil subpopulations with varying functions have been described, and we hypothesize that NB1 antigen may play an important role in neutrophil function. We compared the function of NB1-positive and NB1-negative neutrophils obtained from several persons. There were no differences in the adhesion of NB1-positive and NB1-negative neutrophils incubated in C5a, N-formyl-Met-Leu-Phe (FMLP), phorbol myristate acetate (PMA), or buffer to type IV collagen, fibronectin, laminin, or polystyrene. However, the adherence to human umbilical vein endothelial cells (HUVEC) monolayers of unstimulated NB1-positive neutrophils was less than to NB1-negative neutrophils (20.0% +/- 4.2% vs 31.7% +/- 5.8%; p < 0.01). When neutrophils were stimulated with C5a, PMA, or FMLP, no differences were found in the adhesion of NB1-positive and NB1-negative cells to the same surfaces. When NB1-positive neutrophils were incubated with rabbit polyclonal anti-NB1 Fab fragments, their adherence to HUVEC was increased (32.9% +/- 10.1% vs 18.3% +/- 5.0%; p < 0.05). Fab fragments prepared from normal rabbit serum had no effect on neutrophil adherence to HUVEC. The chemotaxis of NB1-positive neutrophils to FMLP through nitrocellulose was significantly greater than that of NB1-negative neutrophils (p = 0.03), but there was no difference in chemotaxis to FMLP through polycarbonate membranes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Structure-activity relationships of the 7-substituents of 5,4'-diamino-6,8,3'-trifluoroflavone, a potent antitumor agent

Recently, we reported that 5,4'-diamino-6,8,3'-trifluoroflavone (1b) exhibits potent antitumor activity against certain types of human cancer cell lines both in vitro and in vivo. Since the antiproliferative activity of 5,4'-diaminoflavone (1a), the lead compound of 1b, was modulated by the addition of apigenin, we hypothesized that the 7-position is important for the interaction with a putative target molecule. On the basis of this hypothesis, the structure-activity relationships of the substituents at the 7-position of 1b were explored. As a result, 7-methyl (7a), 7-hydroxymethyl (7l), 7-(acyloxy)methyl (9a,c,e,g,j), and 7-aminomethyl (12f) derivatives were found to exhibit comparable or superior antitumor activity to compound 1b against MCF-7 cells both in vitro and in vivo (po administration). In particular, compounds 9e,g,j, and 12f were sufficiently water-soluble as compared with 1b which hardly solubilizes in water. A lipophilic 7-(hexanoyloxy)methyl derivative (9c) was also found to exhibit strong antitumor activity especially in vivo. Since the modes of action and the target molecule(s) are unknown, a mechanistic study will be important in the future.     

Following the Wrong Footsteps: Fixation Effects of Pictorial Examples in a Design Problem-Solving Task.

Two experiments examined possible negative transfer in nonexperts from the use of pictorial examples in a laboratory design problem-solving situation. In Experiment 1, 89 participants were instructed to "think aloud" and were assigned to 1 of 3 conditions: (a) control (standard instructions), (b) fixation (inclusion of a problematic example, describing its problematic elements), or (c) defixation (inclusion of a problematic example, with instructions to avoid using problematic elements). Negative transfer due to examples was measured both quantitatively and qualitatively through verbal protocols. Verbal protocols (N = 176) were analyzed for participants' reasons for reference to the examples. In Experiment 2, fixation to examples was evaluated in nonverbalizing participants (N = 60). Results of both experiments suggest that (a) although participants consulted the problem instructions, they tended to follow the examples even when they included inappropriate elements and (b) the fixation effects can be diminished with the use of defixating instructions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Equivalence of alternate forms of six psychometric measures during repeated testing.

Analysis of scores obtained by 80 army enlisted men on the 1st 7 forms of the 6 repetitive psychometric measures developed by L. Moran and R. Mefferd (see record 1960-02367-001) indicates that (a) different forms measure the same factors, (b) the Forms * S Groups interaction effects were significant, and (c) there was an unexpected practice effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Use of organic cosmotropic solutes to crystallize flexible proteins: application to T7 RNA polymerase and its complex with the inhibitor T7 lysozyme

We have crystallized, using several approaches that may be of general interest, T7 RNA polymerase (T7RP) and the T7 RNA polymerase-T7 lysozyme complex (T7RPL) in forms suitable for structure determination by X-ray crystallography. A series of polyhydric alcohols, sugars, amino and methylamino acids, compounds known to stabilize protein structure, were found to be critical for both crystallization and subsequent improvement of the crystal's diffraction resolution. Moreover, optimal crystallogenesis was achieved through an unconventional "reverse" vapor diffusion sitting drop method that is suitable for proteins that are insoluble at low ionic strength.T7RP has been crystallized in an orthorhombic form (I), space group P222, with cell parameters a=220 A, b=205 A, c=67 A and a monoclinic form (II), space group P21, with cell parameters a=229 A, b=205 A, c=70 A, beta=106 degrees. Crystal form I diffracts X-rays to 3.5 A and form II to 6.0 A. Three and six copies of the polymerase are predicted to be in the asymmetric unit forms I and II, respectively. Three monoclinic crystal forms of the T7RPL complex have been obtained in space group C2. Form I has cell parameters a=320 A, b=93 A, c=229 A, beta=129 degrees, form II has parameters a=293 A, b=93 A, c=68 A, beta=93 degrees, and form III has parameters a=270 A, b=93 A, c=63 A, beta=103 degrees. Crystal form I diffracts synchrotron wiggler radiation to 3.2 A and form III to 2.8 A. Calculations of crystal density imply three or four copies of the complex in form I and one copy in the asymmetric unit of forms II and III.     

Synthesis and calcium channel modulating effects of isopropyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(thienyl)-5-pyridinecarboxylates

A group of racemic isopropyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(thienyl)-5-pyridinecarboxylates++ + 7a-f were prepared using a modified Hantzsch reaction that involved the condensation of a thienylcarboxaldehyde 4a-f with isopropyl 3-aminocrotonate 5 and nitroacetone 6. In vitro calcium channel antagonist activities were determined using a guinea pig ileum longitudinal smooth muscle (GPILSM) assay. Compounds 7a-f exhibited weaker calcium channel antagonist activity (IC50 = 10(-5) to 10(-7) M range) than the reference drug nifedipine (IC50 = 1.43 x 10(-8) M). The point of attachment of the C-4 thienyl ring system was a determinant of antagonist activity [3-thienyl (7b) > 2-thienyl (7a)]. A 5-substituent in the 2-thienyl moiety influenced antagonist activity where the potency order was 5-bromo-2-thienyl 7f > or = 5-methyl-2-thienyl 7c > 2-thienyl 7a. Although the 5-methyl-2-thienyl 7c and 3-methyl-2-thienyl 7d isomers are equipotent antagonists, the 5-bromo-2-thienyl compound 7f appears to be marginally more active than the 4-bromo-2-thienyl isomer 7e. The 2-thienyl compound 7a, unlike the 3-thienyl isomer 7b, exhibited an agonist effect on GPILSM in the absence of the muscarinic agonist carbachol. Effects of the 2-thienyl 7a and 3-thienyl 7b isomers on the magnitude of calcium current were determined in guinea pig ventricular myocytes with voltage clamp techniques. Results showed that 2-thienyl 7a inhibited calcium current (antagonist) when voltage steps were made from a potential of -40 mV. However, when voltage steps were made from -60 mV, 7a enhanced calcium current (agonist). The 3-thienyl isomer 7b had little, if any, effect on calcium current.     

Current results of the treatment of cervical metastatic lymph nodes by concurrent hyperfractionation of carboplatin and irradiation

The results of the treatment of metastatic neck nodes is evaluated after a mean follow-up of 24 months (maximum 45 months). Fifty-seven patients with epidermoid carcinoma of the head and neck were treated according to a hyperfractionated chemoradiation schedule including two fractions a day. Each fraction consisted of 10 mg carboplatin + 115 cGy. Two fractions were given each day, five days a week, for a total dose of 700 mg carboplatin + 8050 cGy. Whenever possible, surgical salvage was performed if treated nodes persisted or recurred. Ten patients presented with N0, 8 with N1, 7 with N2a, 4 with N2b, 7 with N2c, and 21 with N3. The classification of the primary tumor was: 3 Tx, 6 T2, 9 T3 and 39 T4. One hundred and eleven nodes were treated (62 with a diameter of 1-3 cm, 26 with a diameter of 3-6 cm and 23 with a diameter over 6 cm). Actuarial node controls were: 100% for N0, 97% for nodes 1-3 cm, 87% for nodes 3-6 cm, 95% for nodes over 6 cm and 97% for the whole group. The actuarial local-regional control was 71% and the disease-free survival was 60%. These results include 5 surgical salvages (11% of N+), 2 of which recurred again (40%), while another 3 (60%) did not recur.     

Resurfacing of the donor defect after wrap-around toe transfer with a free lateral forearm flap

BACKGROUND: One-week proton pump inhibitor-based triple therapies are very popular in the US despite limited US data documenting efficacy. We assessed 1-week proton pump inhibitor triple therapies for Helicobacter pylori, and compared them to dual antibiotic therapies (to assess benefit of omeprazole) and to omeprazole-amoxycillin (to assess benefit of clarithromycin) in a large, randomized, US multicentre study. METHODS: Healthy subjects who were H. pylori-positive by rapid serological test and 13C-urea breath test were randomly assigned to (i) omeprazole (O) 20 mg b.d. + amoxycillin (A) 1 g t.d.s. for 14 days (OA); (ii) A 1 g b.d. + clarithromycin (C) 500 mg b.d. for 7 days (AC); (iii) C 250 mg b.d. + metronidazole (M) 500 mg b.d. for 7 days (CM); (iv) O 20 mg b.d. + C 250 mg b.d. + M 500 mg b.d. for 7 days (MOC); or (v) O 20 mg b.d. + C 500 mg b.d. + A 1 g b.d. for 7 days (OAC). Repeat breath tests were done at 6 weeks to assess H. pylori status. RESULTS: Three hundred and two H. pylori-positive subjects at 25 centres received medication. Intention-to-treat cure rate was significantly higher for OAC (82%) than for MOC (67%), CM (59%), AC (18%) or OA (58%), Per-protocol cure rates were 85% for OAC and 75% for MOC. Discontinuation of therapy due to a side-effect occurred in 0-3% of each study group. CONCLUSIONS: One-week twice-daily triple therapy with omeprazole, amoxycillin and clarithromycin provides the best rate of eradication of the five regimens studied. However, treatment in the US for 7 days may be unable to achieve eradication rates of > or = 90% with proton pump inhibitor-based triple therapy.     

Referential Communication by Chimpanzees (Pan troglodytes).

Two experiments were conducted to assess the referential function of chimpanzee (Pan troglodytes) gestures to obtain food. The chimpanzees received 1 trial per condition. In Experiment 1 (N = 101), in full view of the chimpanzee, a banana was placed on top of 1 of 2 inverted buckets or was hidden underneath 1 of the buckets. In Experiment 2 (N = 35), 4 conditions were presented in constant order: (a) no food, no observer; (b) no food, observer present; (c) food present, no observer; and (d) food present, observer present. Gestures and visual orienting were used socially and referentially. The capacity for nonverbal reference may predate the Hominidae-Pongidae split, and the development of nonverbal reference may be independent of human species-specific adaptations for speech. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Exonuclease enhances hybridization efficiency: improved direct cycle sequencing and point mutation detection

The title compounds (6-9) were prepared and evaluated for serotonin 5-HT4 agonistic activity in in vitro tests. Introducing a propyl or allyl group at the 3-position of benzamide caused only a slight enhancement of agonistic activity. Construction of the benzo[b]furan skeleton and 2,3-dihydrobenzo[b]furan skeleton caused a significant enhancement of the activity. 4-amino-N-[2-(1-azabicyclo[3.3.0]octan-5-yl)ethyl]-5-chloro- 2-methylbenzo[b]furan-7-carboxamide (7b) hemifumarate was as potent as cisapride. 4-Amino-N-[2-(1-azabicyclo[3.3.0]octan-5-yl)ethyl]-5-chloro- 2,3-dihydro-2-methylbenzo[b]furan-7-carboxamide (8a) hemifumarate, 4-amino-N-[2-(1-azabicyclo[3.3.0]octan-5-yl)ethyl]-5-chloro- 2,3-dihydro-2-ethylbenzo[b]furan-7-carboxamide (8c) hemifumarate, and 4-amino-N-[2-(1-azabicyclo[3.3.0]octan-5-yl)ethyl]-5-chloro- 2,3-dimethylbenzo[b]furan-7-carboxamide (8d) hemifumarate were more potent than cisapride. Furthermore, 8a hemifumarate was free from dopamine D1, D2, serotonin 5-HT1, 5-HT2 and muscarine M1, M2 receptor binding activity in the in in vitro tests. On the other hand, construction of the indole skeleton caused a remarkable decrease in activity.     

Echocardographic features of papillary fibroelastoma and their consequences and management

Clone CL Brener is the reference organism used in the Trypanosoma cruzi Genome Project. Some biological parameters of CL Brener were determined: (a) the doubling time of epimastigote forms cultured in liver infusion-tryptose (LIT) medium at 28 degrees C is 58 +/- 13 hr; (b) differentiation of epimastigotes to metacyclic trypomastigotes is obtained by incubation in LIT-20% Grace's medium; (c) trypomastigotes infect mammalian cultured cells and perform the complete intracellular cycle at 33 and 37 degrees C; (d) blood forms are highly infective to mice; (e) blood forms are susceptible to nifurtimox and benznidazole. The molecular typing of CL Brener has been determined: (a) isoenzymatic profiles are characteristic of zymodeme ZB; (b) PCR amplification of a 24S alpha ribosomal RNA sequence indicates it belongs to T. cruzi lineage 1; (c) schizodeme, randomly amplified polymorphic DNA (RAPD) and DNA fingerprinting analyses were performed.     

A cluster of basic residues in the carboxyl-terminal tail of the short metabotropic glutamate receptor 1 variants impairs their coupling to phospholipase C

Among phospholipase C-coupled metabotropic glutamate receptors (mGluRs), some have a surprisingly long carboxyl-terminal intracellular domain (mGluR1a, -5a, and -5b), and others have a short one (mGluR1b, -1c, and -1d). All mGluR1 sequences are identical up to 46 residues following the 7th transmembrane domain, followed by 313, 20, 11, and 26 specific residues in mGluR1a, mGluR1b, mGluR1c, and mGluR1d, respectively. Several functional differences have been described between the long isoforms (mGluR1a, -5a, and -5b) and the short ones (mGluR1b, -1c, and -1d). Compared with the long receptors, the short ones induce slower increases in intracellular Ca2+, are activated by higher concentration of agonists, and do not exhibit constitutive, agonist-independent activity. To identify the residues responsible for these functional properties, a series of truncated, chimeric, and mutated receptors were constructed. We found that the deletion of the last 19 carboxyl-terminal residues in mGluR1c changed its properties into those of mGluR1a. Moreover, the exchange of the long carboxyl-terminal domain of mGluR5a with that of mGluR1c generated a chimeric receptor that possessed functional properties similar to those of mGluR1c. Mutagenesis of specific residues within the 19 carboxyl-terminal residues of mGluR1c revealed the importance of a cluster of 4 basic residues in defining the specific properties of this receptor. Since this cluster is part of the sequence common to all mGluR1 variants, we conclude that the long carboxyl-terminal domain of mGluR1a suppresses the inhibitory action of this sequence element.     

Novel (N-ferrocenylmethyl)amines and (N-ferrocenylmethylen)imines derived from vicinal steroid amino alcohols and amines: synthesis, molecular structure, and biological activity

Novel steroidal (N-ferrocenylmethyl)amines with potential biologic activity and of potential interest as chiral ligands for metal complexation were synthesized. The new compounds were screened in vitro for their potential as antimicrobial agents. The synthesis of the new steroidal ferrocenes, including two X-ray crystal structures and biologic assays, are described. The 16-(ferrocenylmethyl)amino-estratrienes 4a-d, 7b, and 10b exhibited outstanding broad antimicrobial activity particularly against mycobacteria and multi-resistant staphylococci. Thus, they can be considered as new lead structures. In contrast, the analogous 3 alpha-(ferrocenylmethyl)amino-cholestanes 12 possessed only weak activity. The reaction of the four isomeric amino alcohols 1a-d (Scheme 1) with ferrocenecarbaldehyde was studied. 1b and 1c with 16/17-trans configuration yielded nearly quantitatively the (E)-Schiff bases 2b and 2c (Scheme 2). In contrast to the trans-compounds, condensation of the cisconfigurated amino alcohols 1a and 1d furnished tautomeric mixtures of the Schiff bases (2a and 2d, respectively) and their corresponding 1,3-oxazolidines (3a and 3d, respectively). The novel (N-ferrocenylmethyl)amines 4a-d were obtained in excellent yields by reduction of the tautomer mixtures and the uniform Schiff bases with sodium borohydride in ethanol. Starting with the 16 beta-hydroxy compound 5a, the synthesis of 16 beta- and 16 alpha-amino-3-methoxy-estra-1,3,5(10)-triene (6b, 9b) is described. The corresponding 16-(N-ferrocenylmethyl)amines 7b and 10b and the 3 alpha-(N-ferrocenylmethyl)amino-cholestanes 12 were synthesized (Scheme 3) for comparison in biologic tests.