Spirobicyclic System Research Articles

A rare type of sesquiterpene and β-santalol derivatives from Santalum album and their cytotoxic activities.

A rare type of sesquiterpene with a spiro bicyclic system (1) and seven new (2-8) and four known (9-12) β-santalol derivatives were isolated from the heartwood of Santalum album (Santalaceae). The structures of these new compounds were determined by analysis of extensive spectroscopic data. The isolated compounds and derivatives were evaluated for their cytotoxic activity against HL-60 human promyelocytic leukemia cells, A549 human lung adenocarcinoma cells, HSC-2 and HSC-4 human oral squamous cell carcinoma cell lines, and TIG-3 normal human diploid fibroblasts. cis-β-Santalol (9) and β-santaldiol (10) induced apoptotic cell death in HL-60 cells.

Anomalous Regioselective Four‐Member Multicomponent Biginelli Reaction II: One‐Pot Parallel Synthesis of Spiro Heterobicyclic Aliphatic Rings.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Anomalous regioselective four-member multicomponent Biginelli reaction II: one-pot parallel synthesis of spiro heterobicyclic aliphatic rings.

In a previous preliminary study, we found that a cyclic five-member ring beta-keto ester (lactone) reacts with one molecule of urea and two of aldehyde to give a new family of spiro heterobicyclic aliphatic rings in good yields with no traces of the expected dihydropyrimidine (Biginelli) products. The reaction is driven by a regiospecific condensation of two molecules of aldehyde with urea and beta-keto-gamma-lactone to afford only products harboring substitutions exclusively in a syn configuration (Byk, G.; Gottlieb, H. E.; Herscovici, J.; Mirkin, F. J. Comb. Chem. 2000, 2, 732-735). In the present work ((a) Presented in part at ISCT Combitech, October 15, 2002, Israel, and Eurocombi-2, Copenhagen 2003 (oral and poster presentation). (b) Also in American Peptide Society Symposium, Boston, 2003 (poster presentation). (c) Abstract in Biopolymers 2003, 71 (3), 354-355), we report a large and exciting extension of this new reaction utilizing parallel organic synthesis arrays, as demonstrated by the use of chiral beta-keto-gamma-lactams, derived from natural amino acids, instead of tetronic acid (beta-keto-gamma-lactone) and the potential of the spirobicyclic products for generating "libraries from libraries". Interestingly, we note an unusual and important anisotropy effect induced by perpendicular interactions between rigid pi systems and different groups placed at the alpha position of the obtained spirobicyclic system. Stereo/regioselectivity of the aldehyde condensation is driven by the nature of the substitutions on the starting beta-keto-gamma-lactam. Aromatic aldehydes can be used as starting reagents with good yields; however, when aliphatic aldehydes are used, the desired products are obtained in poor yields, as observed in the classical Biginelli reaction. The possible reasons for these poor yields are addressed and clarify, to some extent, the complexity of the Biginelli multicomponent reaction mechanism and, in particular, the mechanism of the present reaction. Finally, we have investigated and proposed a mechanism for this new reaction by intercepting several intermediates.

Organolead(IV) derivatives of oxophosphorus ligands.: X-ray structures of monomeric R 2Pb[(OPPh 2) 2N] 2 (R=Me, Ph) and tetrameric [Me 3Pb(O 2PPh 2)] 4

The reaction of R 4− n PbCl n with Na[(OPPh 2) 2N] or K[(OPPh 2)(SPPh 2)N] afforded isolation of Ph 2Pb[(OPPh 2) 2N] 2 ( 1), Ph 2Pb[(OPPh 2)(SPPh 2)N] 2 ( 2), Me 3Pb[(OPPh 2) 2N] ( 3) and Ph 3Pb[(OPPh 2)(SPPh 2)N] ( 4). Attempts to grow crystals of Me 3Pb[(OPPh 2) 2N] ( 3) led to isolation of Me 2Pb[(OPPh 2) 2N] 2 ( 5), as a result of decomposition. Me 3Pb(O 2PPh 2) ( 6) was obtained from Me 3PbCl and Na(O 2PPh 2). The compounds were characterized by IR and multinuclear NMR spectroscopy. The molecular structures of 1, 5 and 6 were determined by single-crystal X-ray diffraction. The crystal of 5 contains two independent molecules in the unit cell. In both compounds the imidodiphosphinato ligands act as monometallic biconnective units, resulting in a spiro-bicyclic system with six-membered PbO 2P 2N rings of distorted boat conformation. The coordination geometry around the metal atom is distorted octahedral, with CPbC angles close to 180° [178.9(2)° for 1; 173.4(3)° and 178.7(4)° for molecules 5a and 5b, respectively]. The crystal of the trimethyllead(IV) phosphinate ( 6) contains discrete tetrameric units, [Me 3Pb(O 2PPh 2)] 4, with bridging phosphinato ligands [range: PbO 2.373(3)–2.402(6) Å, PO 1.495(6)–1.512(6) Å], thus resulting in a sixteen-membered Pb 4O 8P 4 inorganic ring. The coordination geometry at lead atoms is distorted trigonal bipyramidal, with oxygen atoms in trans positions [range: OPbO 174.7(2)–177.6(3)°].

Stereocontrolled preparation of a nonpeptidal (-)-spirobicyclic NK-1 receptor antagonist.

The synthesis of a spirobicyclic NK-1 receptor (Substance-P) antagonist 1 antipode is described. Retrosynthetic analysis reveals an allylic halide A bearing the cyclopropoxy-substituted aryl group and a 2-phenyl-3-piperidone B. The stereochemistry in the spirobicyclic system bearing three chiral centers is initially set via a highly diastereoselective zinc-mediated coupling of the allylic bromide 23 to the optically active ketopiperidine 3. The remaining benzylic asymmetric center is set by a diastereoselective hydroboration followed by cyclization to the spirobicyclic system.

A spirobicyclic complex of Schmidpeter's ligand, bis(tetraphenylimidodiphosphinato)beryllium, Be(OPh2PNPPh2O)2, an inorganic analog of beryllium bis(?-diketonates)

The crystal structure of bis(tetra-phenylimidodiphosphinato)beryllium (as a benzene solvate), Be(OPh2PNPPh2O)2. C6H6, was determined by X-ray diffraction and compared with that of beryllium acetylacetonate, Be(OCMeCHCMeO)2. The imidodiphosphinate is an inorganic spirobicyclic system, Be(OPNPO)2, with tetrahedrally coordinated beryllium. Unlike the planar BeO2C3 rings in the acetylacetonate, the two six-membered BeO2P2N inorganic rings are nonplanar and display a skew boat conformation. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:244–248, 2000

Design, synthesis, and conformational analysis of a novel spiro-bicyclic system as a type II .beta.-turn peptidomimetic

A novel highly constrained spiro-bicyclic system (5) has been developed to mimic the type II β-turn, a secondary structural feature found in many bioactive peptides. This system simultaneously restricts three (Φ 2 , Ψ 2 , and Φ 3 ) of the four torsion angles that characterize the type II β-turn. As a test of the design, the asymmetric synthesis and conformational analysis of derivative 6 starting from (R)-2-allylproline is reported. Temperature dependent NMR chemical shift studies in CDCl 3 suggest that the amide proton of 6 is involved in an intramolecular hydrogen bond.Aso,NOE measurements place this hydrogen under the plane of the bicyclic ring system in proper proximity for this hydrogen bond to form with the acetyl carbonyl oxygen.Modeling studies of 6 produced eight minimum-energy conformations with torsion angles close to those of the classical type II β-turn.A comparison of the minimum-energy conformer of this molecule with the classical type II β-turn gave an RMS fit=0.161 A °