Fe(II)-Induced Fragmentation Reaction of γ-Hydroperoxy-α,β-enones. Part 1. Synthesis of 13(14→8)-abeo-Steroids

Some steroidal analogues embodying the hitherto unknown 13(14→8)-abeo skeleton have been synthesized by Fe(II)-induced rearrangement (tandem β-fission/reductive alkylation) of 14α-hydroperoxy-7-en-6-ones. The configurational assignment was made by thorough analysis of NMR spectra; the structure of one of the products was unambiguously assessed by X-ray single-crystal analysis.     

trans-6-Aminocyclohept-3-enols, a new designed polyfunctionalized chiral building block for the asymmetric synthesis of 2-substituted-4-hydroxypiperidines

trans-6-Aminocyclohept-3-enols 18 and ent-18 are new designed polyfunctionalized chiral building blocks for piperidine alkaloids synthesis and are prepared in high yields from the enzymatically derived cyclohept-3-ene-1,6-diol monoacetate (-)-8. Efficient highly enantioselective syntheses of cis-4-hydroxypipecolic acid (1) and piperidines 3 and 4, in both enantiomeric forms, are described. [reaction: see text]     

Chemo-enzymatic Synthesis of 6″-O-(3-Arylprop-2-enoyl) Derivatives of the Flavonol Glucoside Isoquercitrin

A chemo-enzymatic approach to some 6″-O-(3-arylprop-2-enoyl) derivatives of the flavonol glucoside isoquercitrin ( 2a ) was explored to overcome the inability to directly introduce these acyl moieties by an enzyme-catalyzed reaction of 2a with the corresponding activated esters. This new approach was based on the regioselective introduction of a methyl malonate residue at the CH₂OH of the sugar moiety by catalysis with the protease subtilisin (→ 22a ). The mixed diester 22a was then subjected to chemoselective hydrolysis of the methoxycarbonyl function by another enzyme, biophine esterase (→ 23 ). Finally, the malonic monoester 23 was reacted in a Knoevenagel-type condensation with benzaldehyde, 4-hydroxybenzaldehyde, or 4-hydroxy-3-methoxybenzaldehyde to afford the target 6″-O-(3-arylprop-2-enoyl) isoquercitrins 2b–d .     

Biomolecular free energy profiles by a shooting/umbrella sampling protocol, "BOLAS"

We develop an efficient technique for computing free energies corresponding to conformational transitions in complex systems by combining a Monte Carlo ensemble of trajectories generated by the shooting algorithm with umbrella sampling. Motivated by the transition path sampling method, our scheme "BOLAS" (named after a cowboy's lasso) preserves microscopic reversibility and leads to the correct equilibrium distribution. This makes possible computation of free energy profiles along complex reaction coordinates for biomolecular systems with a lower systematic error compared to traditional, force-biased umbrella sampling protocols. We demonstrate the validity of BOLAS for a bistable potential, and illustrate the method's scope with an application to the sugar repuckering transition in a solvated deoxyadenosine molecule.     

(S)-(+)-N-acetylphenylglycineboronic acid: a chiral derivatizing agent for Ee determination of 1,2-diols

A new chiral derivatizing agent for ee determination of 1,2-diols via (1)H NMR is described. (S)-(+)-N-acetylphenylglycineboronic acid (1) is synthesized in enantiomerically pure form; its reaction with chiral diols quantitatively yields cyclic boronic esters 5a-g. The latter show a remarkably high diastereodifferentiation of proton NMR signals useful for de determination. [reaction: see text]     

Remote control of enzyme selectivity: the case of stevioside and steviolbioside

The remote control of lipase PS site- and regioselectivity by substrate modification has been observed in the acetylation of stevioside (1) and steviolbioside (2): deglucosylation at position C-19 changed the acylation site of the sophorose moiety linked at C-13. In fact, while esterification of 1 gave mainly the corresponding 6″-O-acetylated derivative, acylation of 2 gave exclusively the 6′-O-monoester. A possible rationale has been suggested, based on the conformational behavior of the substrates in different simulated solvents.     

Dipole moments of (CH3)3MX compounds with bonds between halogens and group IV a elements: evidence for pX → dM bonding

The electric dipole moments of the two series of molecules (CH₃)₃MX with M  C, Si, Ge, Sn and Pb, and X  Cl and Br have been determined. The two carbon compounds show behaviour different from that of the others, and this is interpreted as indicating that p_X → d_M back-bonding is present for the other elements of the series, and it is suggested that the extent of this back-bonding decreases with an increase in the atomic number of M.     

The 1H and 13C nmr spectra of the “onium” salts of dithiacyclophanes

The ¹H and ¹³C nmr spectra of three cyclic sulphonium salts ol dithiacyclophanes have been recorded and compared with those of the open-chain analogue. The ¹H spectra indicate that methylation of the dithiacyclophanes gives a mixture of eonformational isorners with slightly different chemical shifts for the benzylic protons. The ¹³C spectra indicate that the smaller rings adopt an unsymmetrical conformation with respect to the aromatic ring but that in the larger ring studied, the aromatic carbon atoms are magnetically equivalent. The relevance of these results to the reactivity of the aromatic ring is discussed.     

The electronic effect of positively charged substituents on an aromatic ring: a 13cmr and theoretical study

The effects of the substituents -N⁺Me₃, -CH₂N⁺Me₃ and -P⁺Me₃ on the relative ¹³C chemical shifts at meta and para positions accord with the σ_r° values obtained from IR intensities provided the correlation equation of Syrova et al. is used. SCF-MO calculations using a minimal STO-3G basis set suggest that the -N⁺H₃ substituent acts as a weak π-electron donor and the -P⁺H₃ substituent as a π-electron acceptor in accord with the σ_r° constants for the methylated poles. In these calculations, the action of -PH₃⁺ as a π-electron acceptor can be rationalised in terms of an hyperconjugative effect involving the empty π-type group MO, that in -PH₃⁺ is located at a significantly lower energy than in -NH₃⁺. This π-type group MO is formed by suitable combinations of the 3p AO's of P with the 1s AO's of the hydrogens and therefore there is no need to invoke 3d-orbitals participation in -PH₃⁺ to explain this differential behaviour.     

A new approach to (±)-apovincamine

(±)-Apovincamine ($\text{2}$) is synthesized by dehydration of the β-hydroxyrster ($\text{7}$) obtained by alkylation of the aldehyde ($\text{6}$) with metal chloroacetate