Divergent Synthesis of Novel Cylindrocyclophanes that Inhibit Methicillin-Resistant Staphylococcus aureus (MRSA).

The cylindrocyclophanes are a family of macrocyclic natural products reported to exhibit antibacterial activity. Little is known about the structural basis of this activity due to the challenges associated with their synthesis or isolation. We hypothesised that structural modification of the cylindrocyclophane scaffold could streamline their synthesis without significant loss of activity.

Semi-syntheses of the 11-hydroxyrotenoids sumatrol and villosinol.

We describe semi-syntheses of the 11-hydroxyrotenoids sumatrol (1) and villosinol (2), starting from rotenone (5), using an oxime-directed C11-H functionalisation approach. Thus, rotenone (5) was converted into rotenone oxime (6), which gave dimeric palladacycle 7 following reaction with Na2PdCl4·3H2O. Controlled, divergent, oxidation of palladacycle 7 with either Pb(OAc)4 or K2Cr2O7 afforded the 11-acetoxylated intermediates 9 and 13, respectively, which were transformed into sumatrol (1) and villosinol (2).

Stereocontrolled semi-syntheses of deguelin and tephrosin.

We describe stereocontrolled semi-syntheses of deguelin and tephrosin, anti-cancer rotenoids isolated from Tephrosia vogelii. Firstly, we present a new two-step transformation of rotenone into rot-2'-enonic acid via a zinc-mediated ring opening of rotenone hydrobromide. Secondly, following conversion of rot-2'-enonic acid into deguelin, a chromium-mediated hydroxylation provides tephrosin as a single diastereoisomer.

Carbenoid-mediated nucleophilic "hydrolysis" of 2-(dichloromethylidene)-1,1,3,3-tetramethylindane with DMSO participation, affording access to one-sidedly overcrowded ketone and bromoalkene descendants(§).

2-(Dichloromethylidene)-1,1,3,3-tetramethylindane was "hydrolyzed" by solid KOH in DMSO as the solvent at ≥100 °C through an initial chlorine particle transfer to give a Cl,K-carbenoid. This short-lived intermediate disclosed its occurrence through a reversible proton transfer which competed with an oxygen transfer from DMSO that created dimethyl sulfide. The presumably resultant transitory ketene incorporated KOH to afford the potassium salt of 1,1,3,3-tetramethylindan-2-carboxylic acid (the product of a formal hydrolysis).

Organometallic cages as vehicles for intracellular release of photosensitizers.

Water-soluble metalla-cages were used to deliver hydrophobic porphin molecules to cancer cells. After internalization, the photosensitizer was photoactivated, significantly increasing the cytotoxicity in cells. During the transport, the photosensitizer remains nonreactive to light, offering a new strategy to tackle overall photosensitization, a limitation often encountered in photodynamic therapy.

Carbenoid chain reactions through proton, deuteron, or bromine transfer from unactivated 1-bromo-1-alkenes to organolithium compounds.

The deceptively simple vinylic substitution reactions Alk2C=CA-Br + RLi --> Alk2C=CA-R + LiBr (A = H, D, or Br) occur via an alkylidenecarbenoid chain mechanism (three steps) without transition metal catalysis. 2-(Bromomethylidene)-1,1,3,3-tetramethylindan (Alk2C=CH-Br, 2a) is deprotonated (step 1) by phenyllithium (PhLi) to give the Br,Li-alkylidenecarbenoid Alk2C=CLi-Br (3). In the ensuing chain cycle, 3 and PhLi (step 2) form the observable alkenyllithium intermediate Alk2C=CLi-Ph that characterizes the carbenoid mechanism in Et2O and is able to propagate the chain (step 3) through deprotonation of 2a, furnishing carbenoid 3 and the product Alk2C=CH-Ph.

Carbenoid chain reactions: substitutions by organolithium compounds at unactivated 1-chloro-1-alkenes.

The deceptively simple "cross-coupling" reactions Alk(2)C=CA-Cl + RLi --> Alk(2)C=CA-R + LiCl (A = H, D, or Cl) occur via an alkylidenecarbenoid chain mechanism in three steps without a transition metal catalyst. In the initiating step 1, the sterically shielded 2-(chloromethylidene)-1,1,3,3-tetramethylindans 2a-c (Alk(2)C=CA-Cl) generate a Cl,Li-alkylidenecarbenoid (Alk(2)C=CLi-Cl, 6) through the transfer of atom A to RLi (methyllithium, n-butyllithium, or aryllithium). The chain cycle consists of the following two steps: (i) A fast vinylic substitution reaction of these RLi at carbenoid 6 (step 2) with formation of the chain carrier Alk(2)C=CLi-R (8), and (ii) a rate-limiting transfer of atom A (step 3) from reagent 2 to the chain carrier 8 with formation of the product Alk(2)C=CA-R (4) and with regeneration of carbenoid 6.

Acute bilateral carpal tunnel syndrome associated with human parvovirus B19 infection.

Human parvovirus B19 has been described as a causative agent of erythema infectiosum (a disease common in children), aplastic crisis in patients with hemolytic disorders, and arthralgias and arthritis. Joint involvement may be a prominent clinical feature of parvovirus B19 infection and may last for several weeks. We describe three cases of acute bilateral carpal tunnel syndrome associated with parvovirus B19 infection as evidenced by serological data and, in one case, by detection of parvovirus B19 DNA in blood with use of PCR.

Intra-hisian 2:1 atrioventricular block secondary to Lyme disease.

We describe a case of Lyme carditis with intra-hisian 2:1 atrioventricular (AV) block documented by electrophysiological study. To our knowledge, only two cases of AV block at the level of the His bundle has been described in the literature. Sinus rhythm was restored after 4 days of i.