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Mixed 1,2,4,5-tetraoxanes possessing simple spirocycloalkane and spirocholic acid-derived substituents were prepared and shown to have significantly higher in vitro antimalarial activity than bis-substituted tetraoxanes. Out of 41 synthesized tetraoxanes, 12 were in vitro more potent against Plasmodium falciparum chloroquine-resistant W2 clone than artemisinin, and the most potent one was 2.4 times as active as arteether. In addition, 9 compounds exhibit higher activity than chloroquine against P. falciparum chloroquine-susceptible D6 clone. Cytotoxicity was assessed for most active compounds against the Vero cell line, showing a cytotoxicity/antimalarial potency ratio of 1/(1400-9500). For the first time, tetraoxanes were screened against Mycobacterium tuberculosis with MICs as low as 4.73 μM against H37Rv strain. Mixed tetraoxanes were synthesized in a simple procedure from cholic acid methyl esters by direct coupling of steroidal gem-dihydroperoxide to simple ketones and further transformed into corresponding acids and amides.

The hydrosilylation reaction enables the production of silicon polymers. Platinum-carbene complexes are reported that catalyze the hydrosilylation reaction of alkenes with remarkable efficiency and exquisite selectivity and avoid the formation of platinum colloids. By-products, typically encountered with previous catalytic systems, are suppressed with these platinum derivatives.

C20H46.40N12O15.70Pr, triclinic, P (1) over bar (No. 2), a = 10.329(2) Angstrom, b = 10.725(3) Angstrom, c = 15.635(4) Angstrom, alpha = 107.05(2)degrees, beta = 90.43(2)degrees, gamma = 93.35(2)degrees, V = 1652.5 Angstrom(3), Z = 2, R-gt(F) = 0.050, wR(ref)(F-2) = 0.149, T = 293 K.

C20H43.50N10O15.50Pr, triclinic, P (1) over bar (No. 2), a = 10.013(2) Angstrom, b = 10.735(2) Angstrom, c = 15.577(4) Angstrom, alpha = 106.72(2)degrees, beta = 90.20(2)degrees, gamma = 93.29(2)degrees, V = 1600.6 Angstrom(3), Z = 2, R-gt(F) = 0.042, wR(ref)(F-2) = 0.113, T = 293 K.

Substituted gramines, in the presence of iotaBuOK, react with acrolein and beta-keto-phosphonates, via a novel sequence involving a multicomponent condensation followed by an anionic polycyclisation cascade, to afford in excellent overall yields, highly functionalised tetracyclic structures akin to the middle core of the manzamines. In this unique process, Lip to eight elementary transformations take place with remarkably high chemo- and stereocontrol. (C) 2002 Elsevier Science Ltd. All rights reserved.

The conjugate addition of nitromethane to enoates prepared from D-(+)-mannitol, substituted at the alpha-position by a methyl or a benzyl group, was investigated. While excellent syn-selectivity (d.e. >90%) was obtained from a-benzyl enoates (used as a mixture of epimers, E/Z=1.8:1), for alpha-methyl enoates the selectivity depended on the stereochemistry of the double bond in the acceptor (d.e. >90% for the (Z)-enoate and 50% for the (E)-enoate). In all cases, a mixture of epimers was formed at the newly generated stereocenter at the a-position. The epimeric syn-adducts were transformed into the corresponding pure alpha,beta,gamma-trisubstituted gamma-butyrolactones by cyclization in acid medium followed by epimerization of the stereocenter at the a-position in DBU/CH2Cl2. When enoates derived from L-tartaric acid were used as acceptors, syn-selective conjugate additions were also observed (d.e. >90% for the (Z)-isomer and 50% for the (E)-isomer). The configuration at the newly generated stereogenic centers were assigned based on X-ray analyses, H-1-H-1 coupling constants and NOE experiments in NMR spectroscopy. (C) 2002 Elsevier Science Ltd. All rights reserved.

Ozonolysis of the Delta(8(14))-unsaturated steroids 1a,b afforded, instead of the expected 8,14-dioxo-8,14-seco derivatives 2a,b two stereoisomeric Delta(7)-unsaturated ozonides 3a,b and 4a,b.

C25H30O3Si, monoclinic, P12(1)1 (No. 4), a = 9.750(1) Angstrom, b = 7.691(1) Angstrom, c = 16.055(2) Angstrom, beta = 102.99(1)degrees, V = 1173.1 Angstrom(3), Z = 2, R-gt(F) = 0.045, wR(ref)(F-2) = 0.125, T = 293 K.

C25H30O3Si, monoclinic, C1c1 (No. 9), a = 10.385(5) Angstrom, b = 16.748(9) Angstrom, c = 13.381(7) Angstrom, beta = 104.10(2)degrees, V = 2257.2 Angstrom(3), Z = 4, R-gt(F) = 0.027, wR(ref)(F-2) = 0.072, T = 293 K.

Syntheses and host-guest properties of tetrabridged phosphorylated cavitands in their iiii (4i) configurations are described, The tetraphosphonato cavitands 2 and 3, with the four P=O bonds oriented inwards (4i stereoisomer) were prepared in 25% and 53% yields respectively, from the corresponding resort[4]arenes, dichloro(phenyl)phosphane oxide and base. The formation of the 4i stereoisomers is solvent-dependent and is attributable to the capability of an ammonium guest to form an inclusion complex. Only the iiio (3io) stereoisomer of 3 was isolated otherwise, in low yield. These phosphonato cavitands, in their 4i configurations, are particularly efficient extractants for metal ions. The free energies of complexation of 3 with alkali metal and ammonium cations in chloroform solution are in the range from -43.3 (Li+) to -52.4 kJ mol(-1) (CH3NH3+). High binding constants, H-1, P-31 and Cs-133 NMR studies in solution and single-crystal X-ray analysis clearly demonstrated that the aromatic cavity of the host and the four hard donor P=O groups act cooperatively to ensure the encapsulation of the cationic guests. In the solid, the 2 . Cs+ complex showed the Cs' ion inside the aromatic cavity, interacting strongly with the four phosphoryl groups. The 2 . CH3NH3+ complex showed the methyl group of the guest oriented inside the cavity, with the stability of the complex supported by a complex H bond pattern involving H2O molecules and the anion.

The title compound, C19H25NO2, was made in order to confirm the absolute configuration of (R)-3-methyl-2-butylamine obtained from commercially available (R/S)-3-methyl-2-butylamine (racemate) after fractional crystallization of its ammonium salt with the optically pure carboxylic acid derivative, (S)-naproxene.

The crystal structure of the title compound, C11H16N4O2S .H2O, a pancreatic B-cell selective K-ATP channel opener, reveals that that the N-alkylsulfonylguanidine moiety of the drug containing the two guanidine NH groups in the same spatial orientation (in parallel) is closely related to the N-alkylcyanoguanidine moiety of pinacidil in the solid state. The results confirm that the title drug may be considered as a hybrid compound between pinacidil and diazoxide. The crystal packing involves four hydrogen bonds which link the drug and water molecules.

C25H23NO3, orthorhombic, P2(1)2(1)2(1) (No. 19), a = 8.804(3) Angstrom, b = 11.005(4) Angstrom, c = 21.222(8) Angstrom, V = 2056.2 Angstrom (3), Z = 4, R-gt(F) = 0.047, wR(ref)(F-2) = 0.116, T = 293 K.

C16H21NO5, triclinic, P (1) over bar (No. 2), a = 11.1540(7) Angstrom, b = 12.936(1) Angstrom, c = 13.844(1) Angstrom, alpha = 70.540(9)degrees, beta = 65.15(1)degrees, gamma = 73.400(8)degrees, V = 1684.0 Angstrom (3), Z = 4, R-gt(F) = 0.074, wR(ref)(F-2) = 0.229, T = 293 K.

C23H27NO3, monoclinic, C121(No. 5), a = 18.153(6)Angstrom, b = 9.754(3) Angstrom, c = 13.682(5) Angstrom, beta = 121.71(4)degrees, V = 2061.0 Angstrom (3), Z = 4, R-gt(F) = 0.044, wR(ref)(F-2) = 0.101, T = 293 K.