北島 満里子

The first enantioselective total synthesis of kopsiyunnanine B, which has a unique folded and complex pentacyclic structure containing six contiguous chiral centers, has been achieved along our originally proposed biosynthetic pathway. The key reaction of this synthesis includes a bioinspired cascade that builds three ring structures and three chiral centers in one step and features the stereoselective reduction of a β-acrylate and oxidation to an oxindole.

The enantioselective total syntheses of (-)-silicine and (-)-20-episilicine, which contain a chiral piperidine with three contiguous chiral centers (D-ring) and a strained seven-membered ring (C-ring) attached to an indole, were achieved. The key steps of these syntheses included a chiral secondary amine-catalyzed formal aza-[3 + 3] cycloaddition reaction and Lewis acid-mediated irreversible ring-closing reaction. In addition, the stereochemistry at C20 was controlled at a later stage in the syntheses.

The first asymmetric total synthesis of the Lycopodium alkaloid senepodine F, which contains a decahydroquinoline ring (AB-ring) and a quinolizidine ring (CD-ring) connected by a methylene tether, has been achieved. The key steps of this synthesis include an organocatalytic asymmetric Diels-Alder reaction, a diastereoselective intramolecular aza-Michael reaction, and an intramolecular SN2 cyclization to construct multisubstituted nitrogen-containing heterocycles. In addition, our total synthesis led to the stereochemical reassignment on the decahydroquinoline ring of senepodine F.

Divergent total syntheses of the hetero-oligomeric iridoid glycosides mainly found in Dipsacus asper were achieved. Thus, loganin (1), which is important as a monomer unit, was efficiently synthesized by stereoselective reductive cyclization using secologanin (2) as a substrate. Sequential condensation reactions of derivatives of 1 and 2 as monomer units led to the first enantioselective total syntheses of the heterooligomers cantleyoside, (E)-aldosecologa-nin, dipsaperine, (3R, 5S)-5-carboxyvincosidic acid 22-loganin ester, and dipsanoside A.

Three new biphenyl ether quinolizidine lactone alkaloids (1–3) and 13 new biphenyl quinolizidine lactone alkaloids (4–16) were isolated from Heimia salicifolia (Lythraceae) together with seven known alkaloids. Their structures were determined by spectroscopic analyses and chemical conversions.

A new cyclopeptide, ophiorrhisine A (1), a new tetrahydroisoquinoline alkaloid, 7',10-dide-O-methylcephaeline (2), two known beta-carboline alkaloids, and four known tetrahydroisoquinoline alkaloids were isolated from Ophiorrhiza nutans (Rubiaceae). Compound 1 is a tetrapeptide possessing a 14-membered paracyclophane ring and a novel N,N,N-trimethyltyrosine residue in the side chain. The stereochemistry at the aryl alkyl ether bond was different from that of other known 14 -membered paracyclophanes. The structure of 2 was established by spectroscopic analysis and semisynthesis.

The in-vitro assessment of antiviral activity against Flu-A, HIV, RS, HSV type-1, HSV type-2, and HCMV provided that ß-carboline scaffold attach to alkyl substituted with oxo, oxy or polyoxy groups can be further developed as antiviral and/or anticancer agents. Screening of the potential cytocidal properties using HL-200 and several other cell-lines was also done.

Mitragyna speciosa Korth., endemic to tropical Southeast Asia, is a species of particular medicinal importance (Jansen and Prast 1988 Raffa et al. 2013). Known as “kratom” in Thailand and “biak-biak” in Malaysia, the leaves have been traditionally used by natives for their opium-like effect and coca-like stimulant ability. A number of Corynanthe-type indole alkaloids have been identified from this plant. Among them, mitragynine (1) and a minor constituent, 7-hydroxymitragynine (2) (Ponglux et al. 1994), are novel opioid agonists having potent analgesic activity and structures that differ from that of morphine (Figure 8.1) (Horie et al. 1995, 2005 Matsumoto et al. 1996a, b, 1997, 2004, 2005a, b, 2006 Takayama 2004 Takayama et al. 2000a, 2002a 2005 Thongpraditchote et al. 1998 Tohda et al. 1997 Tsuchiya et al. 2002 Watanabe et al. 1997, 1999). For this reason, a myriad of chemical studies of Mitragyna alkaloids have been carried out over the years. This chapter covers the syntheses and chemical reactions of Mitragyna alkaloids.