Jaume Vilarrasa

A fast procedure for the reduction of azides and nitro compounds based on the reducing ability of Sn(SR)3-species

Abstract Tin(II) complexes prepared by treatment of SnCl 2 or Sn(SR) 2 with appropriate amounts of RSH and Et 3 N appear to be the best reducing agents for azides (to amines) reported so far. These tin(II) complexes also reduce primary and secondary aliphatic nitro compounds to oximes, usually within minutes at r.t. or hours in cold, and tertiary aliphatic as well as aromatic nitro compounds to afford the corresponding hydroxylamines. In general, azides react more rapidly than nitro substituents, whereas carbonyl groups, sulphoxides, sulphones, nitriles, and esters are practically unreactive under the same conditions. Some mechanistic details of the reaction of Sn(SPh) 3 - with azides and nitro compounds have also been elucidated.

New synthetic tricks. Triphenylphosphine-mediated amide formation from carboxylic acids and azides

Abstract Equimolar amounts of carboxylic acids, aryl or alkyl azides, and Ph3P in refluxing benzene (hexane, toluene) afford amides in good yields. Insolubility of zwitterions Ph3P+-NH(CH2)nCOO-, arising from μ-azido acids and Ph3P, limits the utilization of the method for lactame formation.

Control of neurotransmitter release by an internal gel matrix in synaptic vesicles

Neurotransmitters are stored in synaptic vesicles, where they have been assumed to be in free solution. Here we report that in Torpedo synaptic vesicles, only 5% of the total acetylcholine (ACh) or ATP content is free, and that the rest is adsorbed to an intravesicular proteoglycan matrix. This matrix, which controls ACh and ATP release by an ion-exchange mechanism, behaves like a smart gel. That is, it releases neurotransmitter and changes its volume when challenged with small ionic concentration change. Immunodetection analysis revealed that the synaptic vesicle proteoglycan SV2 is the core of the intravesicular matrix and is responsible for immobilization and release of ACh and ATP. We suggest that in the early steps of vesicle fusion, this internal matrix regulates the availability of free diffusible ACh and ATP, and thus serves to modulate the quantity of transmitter released.

Asymmetric acetate aldol reactions in connection with an enantioselective total synthesis of macrolactin A

Abstract Asymmetric aldol-like reactions of cinnamaldehyde, dienal 3 (fragment C7-C12 of macrolactin A), and dienal 4 (fragment C15-C24) with (i) chiral acetylthiazolidinethione-derived enolates, (ii) chiral boron enolates, and (iii) silyl enolates in the presence of chiral titanium-2,2′-dinaphthol complexes are compared. Use of the thiazolidinethione auxiliary and TiCl 4 shows practical advantages; e.g., C5-C12 fragment 7 has been isolated enantiomerically pure in 74% yield.

Evaluation of the anti-HIV activity of statins

Recent data suggest that statins block HIV-1 replication, which may have important implications for an alternative treatment for AIDS. We tested different statins in cell culture against HIV and conducted a pilot study in HIV-positive patients receiving simvastatin. No anti-HIV activity was detected at subtoxic concentrations and simvastatin did not induce a significant change in the mean viral load or CD4 cell count in study patients. We caution on the use of statins as antiretroviral agents.

Cleavage of tert-butyldimethylsilyl ethers by chloride ion

A general method for the selective cleavage of tert-butyldimethylsilyl ethers in the presence of tert-butyldiphenylsilyl ones has been established using a combination of H2O and a concentrated solution of LiCl in DMF at 90 °C. Since no acids, bases, reducing or oxidizing agents are used, the method seems to be very appropiate for the deprotection of TBDMS ethers in the presence of other sensitive functional groups.

New Synthetic “tricks”. [Et3NH][Sn(SPh3)] and Bu2SnH2, two useful reagents for the reduction of azides to amines

Treatment of Sn(SPh)2 with PhSH and Et3N affords a tin(II) complex, soluble in organic solvents, which is the best reducing agent for azides reported so far. Bu2SnH2, although not so reactive, also shows several advantages with regard to the standard reducing agents for azides, such as its solubility in most solvents or its scarce reactivity with water.

Stereocontrolled Total Synthesis of Amphidinolide X via a Silicon-Tethered Metathesis Reaction

Two esterifications and an RCM to create the challenging trisubstituted C12-C13 double bond were required in the total synthesis of amphidinolide X (1) reported here. Assembling the three fragments in this order, no RCM occurred or the process yielded mainly isomer Z. However, generating the E double bond first, by a new variant of a Si-tethered metathesis (using Schrocks catalyst), and carrying out the esterification and macrolactonization steps later, 1 was obtained exclusively.

One-pot conversion of azides to Boc-protected amines with trimethylphosphine and Boc-ON

Abstract Reaction of azides with trimethylphosphine followed by addition of 2-(tert-butoxycarbonyloxyimino)-2-phenyl-acetonitrile (Boc-ON) at −20 °C and stirring at r.t. for 5 h affords the desired Boc-amines in 87–100% yields. Similar yields are obtained by mixing all components together (azide, Me3P, and Boc-ON) in toluene or THF.

Alternative procedures for the macrolactamisation of ω-Azido Acids

ω-Azido acids, after activation of the carboxyl groups as mixed anhydrides, N3(CH2)nCOOCOAr (Ar = 3,5-dinitrophenyl or 2,4,6-trichlorophenyl), can be converted to macrolactams in good yields by treatment with Bu3P under high-dilution conditions; the presence of 4-dimethylaminopyridine improves slightly the yields. Amides and peptides can be readily obtained by this procedure.