Kunihiko Mohri

Biomimetic total synthesis of (+/-)-8-oxoerymelanthine.

Erymelanthine 1 and 8-oxoerymelanthine 2 are unique erythrina alkaloids containing a pyridine ring. We synthesized (+/-)-8-oxoerymelanthine 2 in 2.0% overall yield using the following key reactions. The characteristic 6-5-6-6-membered ring system was constructed by the stereoselective intermolecular Diels-Alder reaction. Oxidative cleavage of the aromatic D-ring was conducted chemo- and regioselectively by ozonolysis in the presence of BF(3)-etherate. This cleavage site is identical to the site cleaved during the biosynthesis of erymelanthine 1. Nitrogen incorporation was achieved by aminolysis. Conversion of the D-ring pyridone to the corresponding pyridine was efficiently accomplished by palladium-catalyzed reduction of aryl triflate 21. This is not only the first total synthesis of (+/-)-8-oxoerymelanthine 2 (where the D-ring is pyridine) but also, more importantly, a biomimetic total synthesis of an erythrinan D-aza alkaloid.

Facile synthesis and in vitro properties of 1-alkyl- and 1-alkyl-N-propargyl-1,2,3,4-tetrahydroisoquinoline derivatives on PC12 cells

The synthesis of several 1-alkyl-1,2,3,4-tetrahydroisoquinolines, which may play an important role in Parkinsons disease, has been achieved by modified Pictet-Spengler cyclization of the formyliminium ion. The direct cytotoxicity and preventative effects towards MPP(+)-mediated death of PC12 cells were estimated. The cytotoxicities of 1-alkyl-TIQs were apoptotic and depended on their lipophilic properties. Conversely, introducing the N-propargyl substituent reduced cytotoxicity. 1-Methyl-, 1-methyl-N-propargyl- and 1-cyclopropyl-TIQ partially inhibited MPP(+)-induced cell death, whereas relatively large alkyl substituents at the first position did not enhance the viability of PC12 cells. In summary, our findings suggest a crucial role for the N-propargyl functional group for the effective reduction of cytotoxicity, and show the importance of size and lipophilicity of substituents at the 1-position of 1-alkyl-TIQs.

Ring transformation of dimethoxybenzenes to heterocycles by ozonolysis

Dimethoxybenzene derivatives, which have a hydroxyalkyl or an aminoalkyl side-chain, were oxidized with ozone and transformed to heterocycles by ring closure reaction of the oxidative products.

An efficient and convenient synthesis of 4,5,6,7-tetrahydrothieno〔3,2-c〕pyridines by a modified Pictet-Spengler reaction via a formyliminium ion intermediate

A synthesis of N-formyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridines (5) was achieved in a highly efficient manner via trifluoroacetic acid catalyzed cyclization of formyliminium ion (4), which was produced by imination of 2-(2-thienyl)ethylamine (1) and a carbonyl compound (2) using titanium(IV) tetraisopropoxide followed by formylation with acetic-formic anhydride in a one-pot procedure. This modified Pictet-Spengler reaction provides a convenient method for preparing 4,5,6,7-tetahydrothieno[3,2-c]pyridines (6) possessing various substituents at C-4.

Synthesis of 11b-Hydroxy Erythrina Alkaloid, Erythrartine, and Its O-Acetate (Erythrascine?)

Oxidation of an erythrinan akaloid erysotramidine (4) with CAN in AcOH-MeCN gave, in moderate yield, the 11β-acetoxy derivative (5b), which was transformed into erythrartine (8). Its O-acetate (O-acetylerythrartine) was not identical with erythrascine in the 1 H-nmr spectra, presenting an ambiguity on the reported structure of erythrascine

Stereoselective methoxylation at the 11β-position of the erythrinan skeleton: total synthesis of (±)-erythristemine

Treatment of cis-erythrinan-8-one or 1,7-cyclo-cis :erythrinan-8-one with ceric ammonium nitrate in methanol gave the appreciable yields of the corresponding 11β-methoxy compounds; these were converted into the natural 11-oxygenated erythrinan alkaloid, erythristemine, in high yield.