Yoshiki Hamada

Reissert compound studies: the first pyridine reissert compound

Treatment of pyridine with trimethylsilyl cyanide, benzoyl chloride, and aluminium chloride in methylene chloride gave 1-benzoly-2-cyano-1,2-dihydropyridine, providing the first example of a pyridine Reissert compound; several 3-substituted pyridines have also been converted to Reissert compounds.

Syntheses of (−)-Tripterifordin and (−)-Neotripterifordin from Stevioside

We report short syntheses of (-)-tripterifordin and (-)-neotripterifordin, potent inhibitors of HIV replication, from stevioside, a natural sweetener used worldwide. The key transformations are reduction at C13 through the formation of a tertiary chloride and subsequent three-step lactonization including a selective iodination at C20 by the photoreaction of the C19-alcohol. The title compounds were reliably obtained from stevioside in 9 and 11 steps (with 5-7 isolation steps), respectively. Additionally, the related lactone-containing ent-kaurenes, doianoterpenes A and B, and two more natural products were synthesized.

REDUCTION OF HETEROAROMATIC N-OXIDES WITH CARBON DISULFIDE AND ITS REGIOSELECTIVITY

Naphtho[2,1 -b][1,5]naphthyridine 7,11 -dioxide was prepared and deoxygenation of the N-oxide groups with carbon d isu l f ide^SJ was reported. Of the two N-oxide groups, the 11 -oxide was reduced with a 32% yield, whereas the 7-oxide remained unreacted. Molecular orbital calculations were then applied to rationalize the regioselectivity of CS2 reduction of the known heteroaromatic N-oxides. The calculation result revealed that the electrophilic attack of CS2 on the oxygen atom initiates the reaction. Subsequently, the reaction proceeds via a cyclic intermediate. When more than one intermediate is possible, the reaction through the more stable intermediate is preferred. Introduction Various polycyclic and heteroaromatic compounds exhibit mutagenicity and carcinogenicity. For example, benz[a]anthracene(1) and benzo[a]pyrene(2) derivatives are biologically oxidized or reduced and exhibit carcinogenicity, both in vitro and in vivo. On the other hand, some acridine derivatives are known as antileukemic agents(3). We oxidized and reduced naphtho[2,1-b][1,5]naphthyridine (7,11-diazabenzo[a]anthracene) 1_ in connection with the biological interest. Catalytic hydrogenation has been extensively used for the deoxygenation of heteroaromatic N-oxides. Otherwise, trivalent phosphorous compounds are useful reductants with superior selectivity(4). Furthermore, it is known that CS2 is also a mild reductant of the N-oxide group. The selectivity of CS2 is higher than the trivalent phosphorous compounds and it can react only on apositionally limited oxygen atom(5-7). We also have an interest in this selectivity of CS2and synthesized naphtho[2,1 -b][1,5]naphthyridine 7,11 -dioxide 2.having two N-oxide groups in the molecule. We then heated the compound 2_with CS2 in DMF-CH2CI2 mixed solvent and exclusively obtained the 11-deoxy compound 3.. Furthermore, we tried to explain the reaction selectivity using molecular orbital calculations and confirmed that the reaction is initiated by the electrophilic attack of CS2 on the N-oxide group, since the electron density of the oxygen atom has a relation to the reactivity. The reaction must then proceed via a cyclic intermediate as proposed by Seidl(5).