The structure of 3[beta],20[alpha]-bis(dimethylamino)pregn-5-en-18-ol

Abstract. C25H44N20 , M r= 388.6, orthorhombic, P21212 I, a = 6.185 (2), b = 18.123 (2), c = 20.852 (2) A, U= 2337.2 A 3, Z = 4, D x = 1.104 Mg m -a, 2(Cu Ka) = 1.5418 A,/~ = 0.47 mm -~, F(000) = 864, T= 293 K. Final R - 0.038 for 1791 reflections with I >_ 3a(I). Rings A and C are in chair conformation. Ring B is in an 8fl,9a-half-chair conformation. Ring D adopts a conformation in between 13fl,14a-half-chair and 13t-envelope. There is a quasitrans fusion of rings A and B, whilst ring systems B/C and C/D are trans fused about the bonds C(8)-C(9)and C(13)-C(14).

Catalytic Asymmetric Synthesis of alpha,beta-Disubstituted alpha,gamma-Diaminophosphonic Acid Precursors by Michael Addition of alpha-Substituted Nitrophosphonates to Nitroolefins

Michael additions of alpha-substituted nitrophosphonates to various nitroolefins are shown to proceed with high diastereo- and enantioselectivity when catalyzed by a quinine-derived thiourea-tertiary amine bifunctional catalyst and generate alpha,gamma-diaminophosphonic acid precursors with contiguous quaternary and tertiary stereocenters.

Catalytic Aldol-Cyclization Cascade of 3-Isothiocyanato Oxindoles with alpha-Ketophosphonates for the Enantioselective Synthesis of beta-Amino-alpha-hydroxyphosphonates

A cascade aldol cyclization reaction between 3-isothiocyanato oxindoles and alpha-ketophosphonates has been developed for the synthesis of beta-amino-alpha-hydroxyphosphonate derivatives. Catalyzed by a quinine-based tertiary amino-thiourea derivative, this reaction delivers 2-thioxooxazolidinyl phosphonates based on a spirooxindole scaffold bearing two contiguous quaternary stereogenic centers in high yields with excellent diastereo- (up to >20:1 dr) and enantioselectivities (up to >99:1 er).

Expanding the Peptide beta-Turn in alpha gamma Hybrid Sequences: 12 Atom Hydrogen Bonded Helical and Hairpin Turns

Hybrid peptide segments containing contiguous alpha and gamma amino acid residues can form C-12 hydrogen bonded turns which may be considered as backbone expanded analogues of C-10 beta-turns) found in alpha alpha segments. Exploration of the regular hydrogen bonded conformations accessible for hybrid alpha gamma sequences is facilitated by the use of a stereochemically constrained gamma amino acid residue gabapentin (1-aminomethylcyclohexaneacetic acid, Gpn), in which the two torsion angles about C-gamma-C-beta (theta(1)) and C-beta-C-alpha (theta(2)) are predominantly restricted to gauche conformations. The crystal structures of the octapeptides Boc-Gpn-Aib-Gpn-Aib-Gpn-Aib-Gpn-Aib-OMe (1) and Boc-Leu-Phe-Val-Aib-Gpn-Leu-Phe-Val-OMe (2) reveal two distinct conformations for the Aib-Gpn segment. Peptide 1 forms a continuous helix over the Aib(2)-Aib(6) segment, while the peptide 2 forms beta-hairpin structure stabilized by four cross-strand hydrogen bonds with the Aib-Gpn segment forming a nonhelical C-12 turn. The robustness of the helix in peptide 1 in solution is demonstrated by NMR methods. Peptide 2 is conformationally fragile in solution with evidence of beta-hairpin conformations being obtained in methanol. Theoretical calculations permit delineation of the various C-12 hydrogen bonded structures which are energetically feasible in alpha gamma and gamma alpha sequences.

Direct conversion of 13-beta-alkylgonatetraenes into 13-beta-alkylgon-4-en-3-ones

Birch reduction of 8,9-didehydroestradiol-17 beta 3-methyl ether 1 or 9(11)-didehydroestradiol-17 beta 3-methyl ether 2 followed by acid hydrolysis results in a mixture of 19-nortestosterone 8 and 19-nor-9 beta, 10 alpha-testosterone 9 in varying amounts. However, reduction of their acetates with sodium or lithium, tert-butyl alcohol in liquid ammonia and in the presence of aniline affords exclusively 19-nortestosterone. Similarly, 18a-homo-19-nortestosterone 12 is prepared from the acetate of 18a-homoestradiol-17 beta 3-methyl ether, 10.

Structural characterization of folded and extended conformations in peptides containing gamma amino acids with proteinogenic side chains: crystal structures of gamma(n), (alpha gamma)(n) and gamma gamma delta gamma sequences

The crystal structures of nine peptides containing gamma(4)Val and gamma(4)Leu are described. The short sequences Boc-gamma(4)(R)Val](2)-OMe 1, Boc-gamma(4)(R)Val](3)-NHMe 2 and Boc-gamma(4)(S)Val-gamma(4)(R)Val-OMe 3 adopt extended apolar, sheet like structures. The tetrapeptide Boc-gamma(4)(R)Val](4)-OMe 4 adopts an extended conformation, in contrast to the folded C-14 helical structure determined previously for Boc-gamma(4)(R)Leu](4)-OMe. The hybrid alpha gamma sequence Boc-Ala-gamma(4)(R)Leu](2)-OMe 5 adopts an S-shaped structure devoid of intramolecular hydrogen bonds, with both alpha residues adopting local helical conformations. In sharp contrast, the tetrapeptides Boc-Aib-gamma(4)(S)Leu](2)-OMe 6 and Boc-Leu-gamma(4)(R)Leu](2)-OMe 7 adopt folded structures stabilized by two successive C-12 hydrogen bonds. gamma(4)Val residues have also been incorporated into the strand segments of a crystalline octapeptide, Boc-Leu-gamma(4)(R)Val-Val-(D)Pro-Gly-Leu-gamma(4)(R)Val-Val-OMe 8. The gamma gamma delta gamma tetrapeptide containing gamma(4)Val and delta(5)Leu residues adopts an extended sheet like structure. The hydrogen bonding pattern at gamma residues corresponds to an apolar sheet, while a polar sheet is observed at the lone delta residue. The transition between folded and extended structures at gamma residues involves a change of the torsion angle from the gauche to the trans conformation about the C-beta-C-alpha bond.

Conformational Choices for the Stereochemically Constrained gamma-Amino Acid Residue Gabapentin: Theoretical Studies and Correlation With Experimental Results

Gabapentin (1-aminomethylcyclohexaneacetic acid, Gpn) is an achiral, conformationally constrained gamma amino acid residue. A survey of available crystal structures of Gpn peptides reveals that the torsion angles about the C-gamma-C-beta (theta(1)) and C-beta-C-alpha(theta(2)) bonds are overwhelmingly limited to gauche, gauche (g(+)g(+)/g(-)g(-)) conformations. The Gpn residue forms C-7 and C-9 hydrogen bonds in which the donor and acceptor atoms come from the flanking peptide units. In combination with alpha amino acid residues alpha gamma and gamma alpha segments can adopt C-12 hydrogen bonded structures. The conformational choices available to the Gpn residue have been probed using energy calculations, adopting a grid search strategy. Ramachandran phi-psi maps have been constructed for fixed values of theta(1) and theta(2), corresponding to the gauche and trans conformations. The sterically allowed and energetically favorable regions of conformational space have been defined and experimental observations compared. C-7 and C-9 hydrogen bonded conformational families have been identified using a grid search approach in which theta(1) and theta(2) values are varied over a range of +/- 10 degrees about ideal values at 1 degrees intervals. The theoretical analysis together with experimental observations for 59 Gpn residues from 35 crystal structures permits definition of the limited range of conformational possibilities at this gamma amino acid residue. .

Transformation of 16-dehydroprogesterone and 17?-hydroxyprogesterone by Mucor piriformis

Mucor piriformis was used to study the mode of transformation of 16-dehydroprogesterone (I, pregna-4, 16-diene-3, 20-dione) and 17 alpha-hydroxyprogesterone (II, 17 alpha-hydroxypregn-4-ene-3, 20-dione). Biotransformation products formed from I were 14 alpha-hydroxypregna-4, 16-diene-3, 20-dione (Ia), 7 alpha, 14 alpha-dihydroxypregna-4 16-diene-3, 20-dione (Ib), 3 beta, 7 alpha, 14 alpha-trihydroxy-5 alpha-pregn-16-en-20-one (Ic), and 3 alpha, 7 alpha, 14 alpha-trihydroxy-5 alpha-pregn-16-en-20-one (Id). Metabolites Ic and Id appear to be hitherto unknown. Timecourse studies suggested that the transformation is initiated by hydroxylation at the 14 alpha-position (Ia) followed by hydroxylation at the 7 alpha-position (Ib). Microsomes (105,000 g sediment) prepared from 16-dehydroprogesterone-induced cells hydroxylate I to its 14 alpha-hydroxy derivative (Ia) in the presence of NADPH. Incubation of Ia with the organism resulted in the formation of Ib, Ic and Id. Biotransformation products formed from compound II were 17 alpha, 20 alpha-dihydroxypregn-4-en-3-one (IIa), 7 alpha, 17 alpha-dihydroxypregn-4-ene-3, 20-dione (IIb), 6 beta, 17 alpha, 20 alpha-trihydroxypregn-4-en-3-one (IIc) and 11 alpha, 17 alpha, 20 alpha-trihydroxypregn-4-en-3-one (IId). Time-course studies indicated that IIa is the initial product formed, which is further hydroxylated either at the 6 beta or 11 alpha position. Incubation of IIa with the organism resulted in the formation of IIc and IId. Reduction of the 4-en-3-one system and 20-keto group has not been observed before in organisms of the order Mucorales. In addition, M. piriformis has been shown to carry out hydroxylation at the C-6, C-7, C-11 and C-14 positions in the steroid molecules tested.

Transformation of dehydroepiandrosterone and pregnenolone by Mucor piriformis

The mode of transformation of dehydroepiandrosterone (I, 3 beta-hydroxyandrost-5-en-17-one) and pregnenolone (II, 3 beta-hydroxypregn-5-en-20-one) was studied using Mucor piriformis. Biotransformation products formed from I were 3 beta,17 beta-dihydroxyandrost-5-ene (Ia), 3 beta-hydroxyandrost-5-ene-7,17-dione (Ib), 3 beta,17 beta-dihydroxyandrost-5-en-7-one (Ic), 3 beta,7 alpha-dihydroxyandrost-5-en-17-one (Id) and 3 beta,7 alpha,17 beta-trihydroxyandrost-5-ene (Ie). Biotransformation products formed from compound II were 3 beta,7 alpha-dihydroxypregn-5-en-20-one (IIa) and 3 beta,7 alpha,11 alpha-trihydroxypregn-5-en-20-one (IIb). The organism did not carry out isomerization of the 5-en-3 beta-ol to a 4-en-3-one system in the steroid molecules tested. In addition, it failed to carry out 14 alpha-hydroxylation possibly because of the lack of a 4-en-3-one system in I and II, and stereospecific hydroxylation at the C-7 position in I and II.

Manipulation of the Hydration Levels in Minerals of Sodium Cadmium Bisulfate toward the Design of Functional Materials

Several variants of hydrated sodium cadmium bisulfate, Na(2)Cd(2)(SO(4))(3) center dot 3H(2)O, Na(2)Cd(SO(4))(2) center dot 2H(2)O, and Na(2)Cd(SO(4))(2) center dot 4H(2)O have been synthesized, and their thermal properties followed by phase transitions have been invesigated. The formation of these phases depends on the stochiometry and the time taken for crystallization from water. Na(2)Cd(2)(SO(4))(3)center dot 3H(2)O, which crystallizes in the trigonal system, space group P3c, is grown from the aqueous solution in about four weeks. The krohnkite type mineral Na(2)Cd(SO(4))(2) center dot 2H(2)O and the mineral astrakhanite, also known as blodite, Na(2)Cd (SO(4))(2)center dot 4H(2)O, crystallize concomittantly in about 24 weeks. Both these minerals belong to the monoclinic system(space group P2(1)/c). Na(2)Cd(2)(SO(4))(3)center dot 3H(2)O loses water completely when heated to 250 degrees C and transforms to a dehydrated phase (cubic system, space group I (4) over bar 3d) whose structure has been established using ab initio powder diffration techniques. Na(2)Cd(SO(4))(2)center dot 2H(2)O transforms to alpha-Na(2)Cd(SO(4))(2) (space group C2/c) on heating to 150 degrees C which is a known high ionic conductor and remains intact over prolonged periods of exposure to moisture (over six months). However, when alpha-Na(2)Cd(SO(4))(2) is heated to 570 degrees C followed by sudden quenching in liquid nitrogen beta-Na(2)Cd(SO(4))(2) (P2(1)/c) is formed. beta-Na(2)Cd(SO(4))(2) takes up water from the atmosphere and gets converted completely to the krohnkite type mineral in about four weeks. Further, beta-Na(2)Cd(SO(4))(2) has a conductivity behavior comparable to the a-form up to 280 degrees C, the temperature required for the transformation of the beta- to alpha-form. These experiments demonstrate the possibility of utilizing the abundantly available mineral sources as precursors to design materials with special properties.

Experimental study of phase equilibria in the system Cu-Al-Sn

Phase equilibria in the Cu-rich corner of the ternary system Cu-Al-Sn have been re-investigated. Final equilibrium microstructures of 20 ternary alloy compositions near Cu3Al were used to refine the ternary phase diagram. The microstructures were characterized using optical microscopy (OM), x-ray diffraction (XRD), electron probe microanalysis and transmission electron microscopy. Isothermal sections at 853, 845, 833, 818, 808, 803 and 773 K have been composed. Vertical sections have been drawn at 2 and 3 at% Sn, showing beta(1) as a stable phase. Three-phase fields (alpha + beta + beta(1)) and (beta + beta(1) + gamma(1)) result from beta -> alpha + beta(1) eutectoid and beta + gamma(1) -> beta(1) peritectoid reactions forming metastable beta(1) in the binary Cu-Al. With the lowering of temperature from 853 to 818 K, these three-phase fields are shifted to lower Sn concentrations, with simultaneous shrinkage and shifting of (beta + beta(1)) two-phase field. The three-phase field (alpha + beta + gamma(1)) resulting from the binary reaction beta -> alpha + gamma(1) shifts to higher Sn contents, with associated shrinkage of the beta field, with decreasing temperature. With further reduction of temperature, a new ternary invariant reaction beta + beta(1) -> alpha + gamma(1) is observed at similar to 813 K. The beta disappears completely at 803 K, giving rise to the three-phase field (alpha + beta(1) + gamma(1)). Some general guidelines on the role of ternary additions (M) on the stability of the ordered beta(1) phase are obtained by comparing the results of this study with data in the literature on other systems in the systems group Cu-Al-M.

On the SIG-dimension of trees under the L (a)-metric

Let where be a set of points in d-dimensional space with a given metric rho. For a point let r (p) be the distance of p with respect to rho from its nearest neighbor in Let B(p,r (p) ) be the open ball with respect to rho centered at p and having the radius r (p) . We define the sphere-of-influence graph (SIG) of as the intersection graph of the family of sets Given a graph G, a set of points in d-dimensional space with the metric rho is called a d-dimensional SIG-representation of G, if G is isomorphic to the SIG of It is known that the absence of isolated vertices is a necessary and sufficient condition for a graph to have a SIG-representation under the L (a)-metric in some space of finite dimension. The SIG-dimension under the L (a)-metric of a graph G without isolated vertices is defined to be the minimum positive integer d such that G has a d-dimensional SIG-representation under the L (a)-metric. It is denoted by SIG (a)(G). We study the SIG-dimension of trees under the L (a)-metric and almost completely answer an open problem posed by Michael and Quint (Discrete Appl Math 127:447-460, 2003). Let T be a tree with at least two vertices. For each let leaf-degree(v) denote the number of neighbors of v that are leaves. We define the maximum leaf-degree as leaf-degree(x). Let leaf-degree{(v) = alpha}. If |S| = 1, we define beta(T) = alpha(T) - 1. Otherwise define beta(T) = alpha(T). We show that for a tree where beta = beta (T), provided beta is not of the form 2 (k) - 1, for some positive integer k a parts per thousand yen 1. If beta = 2 (k) - 1, then We show that both values are possible.

Fabrication and characterization of poly(methyl methacrylate)/CaCu3Ti4O12 composites

Composites comprising Poly(Methyl Methacrylate) (PMMA) and CaCu3Ti4O12 (CCTO) via melt mixing followed by hot pressing were fabricated. These were characterized using X-ray diffraction, thermo gravimetric, scanning electron microscopy, and Impedance analyzer for their structural, morphology, and dielectric properties. Composites were found to have better thermal stability than that of pure PMMA. The composite, with 38 Vol % of CCTO (in PMMA), exhibited remarkably low dielectric loss at high frequencies and the low frequency relaxation is attributed to the space charge polarization/MWS effect. Theoretical models were employed to rationalize the dielectric behavior of these composites. At higher temperatures, the relaxation peak shifts to higher frequencies, due to the merging of both beta and alpha relaxations into a single dielectric dispersion peak. The AC conductivity in the high frequency region was attributed to the electronic polarization. POLYM. ENG. SCI., 54:551-558, 2014. (c) 2013 Society of Plastics Engineers