Humilisin E: Strategy for the Synthesis and Access to the Functionalized Bicyclic Core.

Humilisin E is a diterpenoid possessing a rare epoxidized cyclononene trans-fused with a bicyclo[3.2.0]heptane core. We have identified the P atropisomer of the corresponding cyclononadiene as a potential biosynthetic/synthetic precursor to humilisin E and reported two different strategies for the stereocontrolled synthesis of the appropriately functionalized bicyclic cores of humilisin E. The first route involves a Stork epoxynitrile cyclization via a Mg alkoxide, and the second, more stereoselective approach utilizes the Wolff rearrangement as the key step.

Photoactive Yellow Protein Chromophore Photoisomerizes around a Single Bond if the Double Bond Is Locked.

Photoactivation in the Photoactive Yellow Protein, a bacterial blue-light photoreceptor, proceeds via photoisomerization of the double C═C bond in the covalently attached chromophore. Quantum chemistry calculations, however, have suggested that in addition to double-bond photoisomerization, the isolated chromophore and many of its analogues can isomerize around a single C-C bond as well. Whereas double-bond photoisomerization has been observed with X-ray crystallography, experimental evidence of single-bond photoisomerization is currently lacking. Therefore, we have synthesized a chromophore analogue, in which the formal double bond is covalently locked in a cyclopentenone ring, and carried out transient absorption spectroscopy experiments in combination with nonadiabatic molecular dynamics simulations to reveal that the locked chromophore isomerizes around the single bond upon photoactivation. Our work thus provides experimental evidence of single-bond photoisomerization in a photoactive yellow protein chromophore analogue and suggests that photoisomerization is not restricted to the double bonds in conjugated systems. This insight may be useful for designing light-driven molecular switches or motors.

Disseminated histoplasmosis.

Disseminated histoplasmosis is a relentlessly progressive granulomatous disease which can mimic many other granulomatous diseases including tuberculosis. A 48-year-old male was referred to us with 11 months history of multiple subcutaneous swellings and ulcerations over the upper and lower limbs and fever for 2 months. He was evaluated outside for several months and received anti tubercular drugs for about 2 years in the past for a granulomatous infection of bone and soft tissue identified by various biopsies, without any improvement. When he was evaluated and fresh biopsies were taken, they were stained for fungus and disseminated histoplasmosis was detected. This case confirms the importance of considering fungal infections as a possibility while treating disseminated granulomatous infections, even in immune-competent patients, especially if response to treatment is inadequate.