A novel entry to the synthesis of diazoacetates is disclosed. A variety of diazoacetates were synthesized from the corresponding bromoacetates by treatment with N,N'-ditosylhydrazine in moderate to high yields. Ease of operation with the stable crystalline reagent as well as a short reaction time offer a useful alternative to the conventional methods.

The steroidal neurotoxin (-)-batrachotoxin functions as a potent agonist of voltage-gated sodium ion channels (Nas). Here we report concise asymmetric syntheses of the natural (-) and non-natural (+) antipodes of batrachotoxin, as well both enantiomers of a C-20 benzoate-modified derivative. Electrophysiological characterization of these molecules against Na subtypes establishes the non-natural toxin enantiomer as a reversible antagonist of channel function, markedly different in activity from (-)-batrachotoxin. Protein mutagenesis experiments implicate a shared binding side for the enantiomers in the inner pore cavity of Na These findings motivate and enable subsequent studies aimed at revealing how small molecules that target the channel inner pore modulate Na dynamics.

A straightforward synthesis of ecteinascidin 743 was accomplished from readily available l-glutamic acid as a single chiral source. Our novel synthesis features a concise and convergent approach for construction of the B-ring, consisting of a sequence involving a stereoselective Heck reaction between a diazonium salt and an enamide, oxidative cleavage of the resulting alkene, and intramolecular ortho substitution of the phenol by an aldehyde.

A novel synthetic route to (+)-manzamine A was developed. It highlights an amazingly efficient construction of a highly strained 15-membered ring across a cyclohexenone ring with the aim of installing the requisite functionalities in a completely stereocontrolled manner. Other key features include a stereoselective Diels-Alder reaction of an optically active butenolide, construction of the 15-membered ring by intramolecular Mitsunobu reaction of a nosyl amide, [3,3]-sigmatropic rearrangement of allyl cyanate for stereoselective introduction of nitrogen functionality at a sterically congested position, and a ring-closing metathesis in the presence of labile functional groups.

Azo compounds Q 0160 N,N'-Ditosylhydrazine: A Convenient Reagent for Facile Synthesis of Diazoacetates. -A general method for the preparation of a large variety of racemic and chiral diazoacetates is developed. -(TOMA, T.; SHIMOKAWA, J.; FUKUYAMA*, T.; Org. Lett. 9 (2007) 16, 3195-3197; Grad. Sch. Pharm. Sci., Univ. Tokyo, Bunkyo, Tokyo 113, Japan; Eng.) -R. Steudel 49-082