Formal total synthesis of (−)-hamigeran B from a chemo-enzymatically prepared building block with quaternary chiral center

A formal total synthesis of (?)-hamigeran B was achieved in 17 steps from commercially available ethyl 2-oxocyclopentanecarboxylate. Carbonyl reductase-catalyzed asymmetric reduction and the subsequent chemical transformations furnished an enantiomerically pure synthetic intermediate, (R)-5-formyl-2-isopropyl-5-methylcyclopent-1-en-1-yl trifluoromethylsulfonate. Suzuki-Miyaura coupling with Gao's arylboronate [2-(2-formyl-3-methoxy-5-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane], under PdCl₂(dppf)?CH₂Cl₂ catalysis, and the subsequent cyclization by way of intramolecular reductive SmI₂-mediated 1,2-diol formation provided a tricyclic skeleton with a tetrasubstituted double bond between C-1 and C-9b. Upon hydrogenation of this double bond, the proper stereochemistry of the remaining chiral centers was established. Exclusive addition of the hydrogen atom from the β-face occurred, owing to the shielding of the α-face with a bulky TBS protective group on the C-4 alcohol. The hydrogenation products were transformed into Clive's synthetic precursor for (?)-hamigeran B.     

Synthesis,characterization, X-ray structure and preliminary in vitro antitumor activity of the nitrosyl complex fac-[RuCl3(NO)(dppf)], dppf = 1,1′-bis(diphenylphosphine)ferrocene

The reaction of RuCl₃NO · 2H₂O with stoichiometric amount of dppf, 1,1′-bis(diphenylphosphino)ferrocene, afforded the new neutral nitrosyl complex fac-[RuCl₃(NO)(dppf)] which was characterized by spectroscopical, electrochemical and X-ray crystallography techniques as well as elemental analysis. The ν_NO band in the IR spectrum is at 1860 cm⁻¹ (CH₂Cl₂ solution) and in the cyclic voltammogram an irreversible wave was observed at −1.35 V, both are characteristics of a nitrosonium (NO⁺) character for the coordinated NO. Additionally, preliminary in vitro antitumor activity against the MDA-MB-231 breast tumor cell line was carried out for the new complex. The initial results indicated an important activity for fac-[RuCl₃(NO)(dppf)] (IC₅₀ = 10 ± 3 μM ). The complex has a higher cytotoxicity than the precursor complex RuCl₃NO · 2H₂O, the free dppf ligand as well as the reference metallodrug cisplatin.     

Synthesis and structural characterisation of novel platinum-based drug candidates with extended functionality by incorporation of bis(diphenylphosphino)ferrocene units as metal chelators

Among the metal-based anticancer drugs, cisplatin (cis-diaminedichloroplatinum(II)) is the most widely used species in therapy. Despite its clinical success, cisplatin still suffers in generating resistance, as well as being highly toxic due to poor selectivity between healthy and sick cells. By molecular design it ought to be possible to generate new cis-platinum compounds with increased selectivity and improved cellular behaviour. In this paper, we report a synthetic pathway for construction of derivatives of 1,1′-bis(diphenylphosphino)-ferrocene, together with their corresponding cis-platinum compounds with the aim testing them for their interaction capacity with respect to various DNA models. We also report a synthetic route for a nucleoside-based cis-platinum compound containing a bidentate ferrocenylphosphine derivative connected through a succinamic-based linker to the 5-position of the heterocyclic moiety of uridine. Our preliminary kinetic investigation of 5-{N-[1-[1′,2-bis(diphenylphosphino)ferrocenyl]ethyl]-N′-[prop-2-yn-3-yl]succinamide} uridinedichloroplatinum(II) showed that this compound reacted faster with the phosphorothioate containing oligonucleotides d(T₆p(S)T₆), with an observed first-order rate constant k_obs=(1.4±0.1)×10⁻⁴ s⁻¹, compared with the G-N7 target in d(T₇GGT₇), for which the observed first-order rate constant is k_obs=(7.2±0.5)×10⁻⁴ s⁻¹.     

Synthesis, structures and some reactions of Ru(CCCCFc)(PP)Cp (PP = dppm, dppe) and related compounds

The compounds Ru(CCCCFc)(PP)Cp [PP = dppe (1), dppm (2)], have been obtained from reactions between RuCl(PP)Cp and FcCCCCSiMe₃ in the presence of KF (1) or HCCCCFc and K[PF₆] (2), both with added dbu. The dppe complex reacts with Co₂(CO)₆(L₂) [L₂ = (CO)₂, dppm] to give 3, 4 in which the Co₂(CO)₄(L₂) group is attached to the outer CC triple bond. The PPh₃ analogue of 3 (5) has also been characterised. In contrast, tetracyanoethene reacts to give two isomeric complexes 6 and 7, in which the cyano-olefin has added to either CC triple bond. The reaction of RuCl(dppe)Cp with HCCCCFc, carried out in a thf/NEt₃ mixture in the presence of Na[BPh₄], gave [Ru{CCC(NEt₃)CHFc}(dppe)Cp]BPh₄ (8), probably formed by addition of the amine to an (unobserved) intermediate butatrienylidene [Ru(CCCCHFc)(dppe)Cp]⁺. The reaction of I₂ with 8 proceeds via an unusual migration of the alkynyl group to the Cp ring to give [RuI(dppe){η-C₅H₄CCC(NEt₃)CHFc}]I₃ (9). Single-crystal X-ray structural determinations of 1, 2 and 4-9 are reported.     

Kinetics of complex formation between palladium(II) acetate and bis(diphenylphosphino)ferrocene

The kinetics of complex formation between palladium(II) acetate, and 1,1’-bis(diphenylphosphino)ferrocene, dppf, in two different deuterated solvents CDCl₃ and DMSO-d₆ were investigated using ³¹P NMR spectroscopy. The mole ratio and the ³¹P-chemical shifts in DMSO-d₆ solution revealed the formation of an intermediate, which is gradually converted into the more stable [Pd(dppf)OAc)₂] species with a dppf acting as a chelate ligand. In the chloroform solution however, the interaction of metal ion and the ligand resulted directly in the formation of [Pd(dppf)OAc)₂] species with a chelating dppf. The rate constant for the complexation reaction was evaluated from computer fitting of the corresponding integration-time data.     

Acylpyrazolone ligands: Synthesis, structures, metal coordination chemistry and applications

This review summarizes the literature on 4-acyl-5-pyrazolone ligands, their synthesis, characterization and coordination chemistry toward main group, transition, lanthanide and actinide metals and relevant applications of their metal complexes.     

Synthesis and structural characterization of a diiron propanedithiolate complex [( μ -PDT)Fe2(CO)5]2[(η 5-Ph2PC5H4)2Fe] containing a bidentate phosphine ligand 1,1′-bis(diphenylphosphino)ferrocene

The reaction of (μ-PDT)Fe₂(CO)₆ (PDT?=?SCH₂CH₂CH₂S) with 1,1′-bis(diphenylphosphino)ferrocene in the presence of the decarbonylating agent Me₃NO·2H₂O afforded [(μ-PDT)Fe₂(CO)₅]₂[(η ⁵-Ph₂PC₅H₄)₂Fe] (1) in 80% yield. The new complex 1 was characterized by elemental analysis, IR, and ¹H-(³¹P-, ¹³C-) NMR spectroscopies. The structure of 1 was determined by single crystal X-ray diffraction analysis; the molecule is centrosymmetric and two cyclopentadienyl (Cp) rings reside in a staggered conformation.     

Syntheses and Crystal Structures of Polynuclear Cu(I) Complexes Containing the 1,1′-Bis-(diphenylphosphino)-ferrocene Ligand

Summary.  The reaction between [Cu(NCMe)₄][PF₆] and 1,1′-bis-(diphenylphosphino)-ferrocene (dppf) in several ratios, solvents, and conditions led to the synthesis and structural characterization of the Cu(I) complexes [Cu(dppf)(Odppf)][PF₆] (1), [(dppf)Cu(μ-dppf)Cu(dppf)][PF₆]₂ (2), and [(dppf)Cu(μ-Cl)₂Cu(dppf)] (3). Although 1 and the cation in 2 were known, the first was structurally characterized for the first time, exhibiting a significant asymmetry in the coordination sphere of Cu(I) owing to the presence of oxygen. In 2, the PF₆ ⁻ anion led to an interesting crystal packing with large open channels containing water. Finally, DFT calculations on a model of 3 showed that its HOMO exhibits, besides Fe, a significant Cu and Cl character, which is reflected in its electrochemical properties. Received July 14, 2000. Accepted July 21, 2000