Total synthesis of cryptophycin-24 (Arenastatin A) amenable to structural modifications in the C16 side chain.

Two efficient protocols for the synthesis of tert-butyl (5S,6R,2E, 7E)-5-[(tert-butyldimethylsilyl)oxy]-6-methyl-8-phenyl-2, 7-octadienoate, a major component of the cryptophycins, are reported. The first utilized the Noyori reduction and Frater alkylation of methyl 5-benzyloxy-3-oxopentanoate to set two stereogenic centers, which became the C16 hydroxyl and C1' methyl of the cryptophycins. The second approach started from 3-p-methoxybenzyloxypropanal and a crotyl borane reagent derived from (-)-alpha-pinene to set both stereocenters in a single step and provided the dephenyl analogue, tert-butyl (5S,6R,2E)-5-[(tert-butyldimethylsilyl)oxy]-6-methyl-2, 7-octadienoate, in five steps. This compound was readily converted to the 8-phenyl compound via Heck coupling. The silanyloxy esters were efficiently deprotected and coupled to the C2-C10 amino acid fragment to provide desepoxyarenastatin A and its dephenyl analogue. The terminal olefin of the latter was further elaborated via Heck coupling. Epoxidation provided cryptophycin-24 (arenastatin A).

Synthesis and evaluation of paclitaxel C7 derivatives: solution phase synthesis of combinatorial libraries.

A novel and efficient two-step, automated solution phase synthesis of a 26-membered combinatorial chemistry library of paclitaxel C7 esters was accomplished using the HP 7686 Solution Phase Synthesizer. Results of combinatorial synthesis, purification, analysis, and biological evaluation are described.

Intraocular pressure in leprosy patients without clinically apparent anterior segment pathology.

A widely prevalent notion is that intraocular pressures are generally lower in leprosy patients than in normal individuals. Applanation intraocular pressures were recorded in one hundred sixty-six leprosy patients who had no clinically visible anterior segment pathology and in one hundred and eleven healthy controls. Mean (SD) intraocular pressures in leprosy patients (13.6 (3.0) mm Hg) did not differ significantly from that of controls (13.1 (2.7) mm Hg). Eyes of only 1.5% of the leprosy patients had pressures of 7 mm Hg or less. Correlation coefficients (r) between age, sex and intraocular pressures were not statistically significant both in leprosy patients and in controls. No statistically significant differences in mean intraocular pressures were noted when leprosy patients were grouped according to the Ridley and Jopling classification. Duration of disease also did not affect the intraocular pressures. Neither did smear positivity or differing bacterial indices. This study questions the widely held belief that low intraocular pressures are a common feature in leprosy and contends that in the era of MDT where ocular complications associated with low intraocular pressures are thought to be less, the occurrence of low intraocular pressure may not be as common a phenomenon as it is believed to be.