Yukio Hitotsuyanagi

4-Aza-2,3-dehydro-4-deoxypodophyllotoxins: simple aza-podophyllotoxin analogues possessing potent cytotoxicity.

4-Aza-2,3-dehydro-4-deoxypodophyllotoxin analogues 3a-n were synthesized through quinolines 2a-n. Comparison of their cytotoxicity against P-388 leukemia cells revealed that the steric effects of the ring B substituents on the activity are greater than the electronic effects, while the presence of a methoxy group on the ring E is not essential to exhibit potent cytotoxicity. Analogues 3a and 3b proved to be more than twice as cytotoxic as natural podophyllotoxin (1).

Conformational analysis of antitumor cyclic hexapeptides, RA series

Abstract Conformational analysis of an antitumor cyclic hexapeptide, RA and its analogues isolated from Rubia akane and R.cordifolia was conducted by the spectroscopic and computational chemical methods. A combination of different homo- and heteronuclear two-dimentional NMR techniques at 500MHz have enabled us to perform complete assignment of the 1H and 13C signals of the two conformers A and B of RA-VII in CDCl3. The structures of the three conformers (A, B and C) in DMSO-d6 were also determined by 2D-NMR techniques, temperature effects on NH protons and NOE experiments. Distances deduced from the NMR measurements were used for the refinements by the restrained molecular dynamics calculations using AMBER program. These conformational analysis showed that these conformers were caused by geometrical isomerization and that the predominant conformer A exhibits a typical type II β-turn structure, which is similar to the crystal structure analyzed by the X-ray diffractions. The reduced biological activity of the N-methyl derivative of RA-VII in comparison to RA-VII may be responsible for the more weakly populated conformer A in solution. Further, the presence of a highly strained 14-membered ring was necessary to maintain the typical type II β-turn structure of conformer A, and the ring system and turn structure were considered to play an important role in its antitumor activity.

Quassinoids from Eurycoma longifolia

Three quassinoids, eurycolactone D (1), eurycolactone E (2) and eurycolactone F (3) were isolated from the roots of Eurycoma longifolia Jack. The structures of 1-3 were elucidated by spectroscopic methods, and that of 3 was further confirmed by X-ray crystallography. The known quassinoids, laurycolactone B (4) and eurycomalactone (5) were also identified.

A facile synthesis of the 4-aza-analogs of 1-arylnaphthalene lignans chinensin, justicidin B, and Taiwanin C

Abstract Reaction of anilines 1a-d with tetronic acid ( 2 ) or 1,3-cyclopentanedione ( 3 ) produced anilinolactones 4a-d and anilinocyclopentenone 5a , respectively, which were then condensed with benzaldehydes to yield 4-aza-1-arylnaphthalene lignan analogs 6–19 .

Synthesis of l,l-cycloisodityrosines by copper(II) acetate-DMAP-mediated intramolecular O-arylation of phenols with phenylboronic acids

Two types of cycloisodityrosines, 11 and 13, were synthesized from commercially available chiral tyrosine derivatives through the copper(II) acetate-DMAP-mediated diaryl ether formation of boronotyrosyltyrosines 8 and 10, respectively.

Eurycolactones A–C, novel quassinoids from Eurycoma longifolia

Abstract Three novel quassinoids, eurycolactones A–C ( 1 – 3 ), were isolated from the roots of Eurycoma longifolia Jack. Their structures were elucidated by interpretation of the spectroscopic data.

Synthesis of (−)-4-aza-4-deoxypodophyllotoxin from (−)-podophyllotoxin

Abstract (−)-4-Aza-4-deoxypodophyllotoxin ( 4 ) was synthesized from (−)-podophyllotoxin ( 1 ) through C-ring cleavage, Curtius rearrangement and intramolecular N -alkylation. Analogue 4 showed potent cytotoxicity against P388 leukemia cells.

Phytochemical constituents from Cassia alata with inhibition against methicillin-resistant Staphylococcus aureus (MRSA).

The methanolic extract of the leaves of CASSIA ALATA was sequentially partitioned in increasing polarity to afford the hexane, chloroform, butanol and residual extract. Crude extracts were evaluated against MRSA using the agar well diffusion assay. The butanol and chloroform extracts both exhibited inhibition against MRSA with inhibition indexes of 1.03 +/- 0.16 and 0.78 +/- 0.07 at the concentration of 50 mg/mL. The butanol extracts were further purified using silica gel and reverse phase chromatography to afford kaempferol ( 1), kaempferol 3- O-beta-glucopyranoside ( 2), kaempferol 3- O-gentiobioside ( 3) and aloe emodin ( 4). The four constituents showed varying degrees of inhibition against MRSA. Both 1 and 4 exhibited MIC (50) values of 13.0 +/- 1.5 microg/mL and 12.0 +/- 1.5 microg/mL, respectively. The kaempferol glycosides 2 and 3 were less active with MIC (50) values of 83.0 +/- 0.9 microg/mL and 560.0 +/- 1.2 microg/mL, respectively. A free hydroxyl group at C-3 of the flavonol structure is a structural requirement for the inhibition of MRSA.

Structures of new alkaloids sessilifoliamides A–D from Stemona sessilifolia

Abstract Four new Stemona alkaloids, sessilifoliamides A–D ( 1–4 ), were isolated from the roots of Stemona sessilifolia, along with five known alkaloids, stenine ( 5 ), 2-oxostenine ( 6 ), stemoninoamide ( 7 ), tuberostemonone ( 8 ), and neotuberostemonol ( 9 ). The structures and absolute configurations of the new alkaloids were determined by the spectral studies (HRMS, IR, 1H, 13C, and 2D NMR), single-crystal X-ray analyses, and chemical correlations. The absolute configuration of 7 was also determined by the modified Moshers method.

DRUPANGTONINE, A NOVEL ANTILEUKEMIC ALKALOID FROM CEPHALOTAXUS HARRINGTONIA VAR. DRUPACEA

Abstract Drupangtonine ( 1 ), a novel Cephalotaxus alkaloid, has been isolated from Cephalotaxus harringtonia var. drupacea , and its structure has been elucidated based on spectroscopic analyses. Compound 1 strongly inhibits the growth of P-388 leukemia cells.