Xiao-Jiang Hao

Chiral ligands derived from abrine. Part 6: Importance of a bulky N-alkyl group in indole-containing chiral beta-tertiary amino alcohols for controlling enantioselectivity in addition of diethylzinc toward aldehydes

A number of chiral beta-amino alcohols possessing a 3-indolylmethyl group have been synthesized from the alkaloid (S)-abrine and elucidated for potency in the catalytic enantioselective ethylation of PhCHO with Et2Zn. In general, the secondary amines 15a-d bearing a dialkylhydroxymethyl group induced (R)-1-phenyl-1-propanol, whereas 15e-g and 18 bearing a diarylhydroxymethyl group favored the (S)-enantiomer. In contrast, the beta-tertiary amino alcohols 20b d and 21 produced (R)-1-phenyl-1-propanol. regardless of the substituents at the carbon bearing the hydroxy group. Enantiomeric excess of 87.5% was obtained for (R)-1-phenyl-1-propanol using ligand 21 as the promoter. Eleven substituted benzaldehydes and naphth-aldehydes were examined for enantioselective ethylation by using 21 and the chiral alcohols were obtained in 93-97% ee, except for o-BrC6H4CHO and p-Me2NC6H4CHO. Excellent enantioselectivity was also observed in the ethylation of cyclohexanecarboxaldehyde (94.8% ee) and 2-thiophenecarboxaldehyde (94.9% ee) by using catalytic 21. The anti 5/4/4-fused tricyclic TS I was proposed to rationalize the asymmetric induction. The diethylhydroxymethyl and N-2-t-butylethyl groups are believed to enforce the preference for the anti-TS(R) I and it results in high enantioselectivity

Effects of spiramine T on antioxidant enzymatic activities and nitric oxide production in cerebral ischemia-reperfusion gerbils.

Spiramine T, an atisine-type diterpene alkaloid isolated from the Chinese herbal medicine Spiraea japonica var. acuta (Rosaceae), was shown to have neuroprotective effects on cerebral ischemia-reperfusion injury. In this study, the effects of spiramine T on antioxidant enzymes and nitric oxide production were evaluated in gerbils subjected to global forebrain ischemia (10 min) and reperfusion (5 days). Spiramine T (1.0 and 2.0 mg kg(-1) i.p.) markedly reduced the content of lipid peroxide (LPO), increased the glutathione peroxidase (GSH-PX) activity, and inhibited the increase of nitric oxidase (NOS) activity and nitric oxide production in the cortex during ischemia-reperfusion in gerbils. These results suggested that the neuroprotective effects of spiramine T were related to modulation of endogenous antioxidant enzymatic activities and reduction of the formation of nitric oxide.

Four New Styryllactones from Goniothalamus leiocarpus

Four new styryllactones, leiocarpin A (1), 7-epi-goniodiol (2), leiocarpin B (3) and leiocarpin C (4), respectively, were isolated from the stem bark of Goniothalamus leiocarpus. Their structures were elucidated by means of spectral method. The relative configurations of 1, 2 and 3 were determined by X-Ray crystallographic analysis. Compounds 2 and 3 possess antitumor activities.

Chiral ligands derived from Abrine .2. Oxazolidines as promoters for enantioselective addition of diethylzinc toward aromatic aldehydes

A number of indole-containing chiral oxazolidines 2a-i have been synthesized from Abrine readily available from the seeds of Abrus precatorius. Catalysis of these oxazolidines for the addition of diethylzinc toward benzaldehyde was examined. A significant role of the substituent(s) in the catalyst on the degree of asymmetric induction was noted. Moderate enantioselectivity up to 59.8% was recorded. Copyright (C) 1996 Published by Elsevier Science Ltd

Antiplatelet aggregation activity of diterpene alkaloids from Spiraea japonica

Six diterpene alkaloids with an atisine-type C(20)-skeleton isolated from the Chinese herbal medicines Spiraea japonica var. acuta and S. japonica var. ovalifolia, as well as eight derivatives of spiramine C and spiradine F were evaluated for the ability to inhibit aggregation of rabbit platelets induced by arachidonic acid, ADP, and platelet-activating factor (PAF) in vitro. The results showed that 12 of the 14 atisine-type diterpene alkaloids significantly inhibited PAF-induced platelet aggregation in a concentration-dependent manner, but had no effect on ADP- or arachidonic acid-induced aggregation, exhibiting a selective inhibition. It is the first report that C(20)-diterpene alkaloids inhibit PAF-induced platelet aggregation. However, spiramine C1 concentration-dependently inhibited platelet aggregation induced by PAF, ADP and arachidonic acid with IC(50) values of 30.5+/-2.7, 56.8+/-8.4 and 29.9+/-9.9 microM, respectively, suggesting a non-selective antiplatelet aggregation action. The inhibitory effect of spiramine C1 on arachidonic acid was as potent as that of aspirin. Primary studies of the structure-activity relationships for inhibition of PAF-induced aggregation showed that the oxygen substitution at the C-15 position and the presence of an oxazolidine ring in spiramine alkaloids were essential to their antiplatelet aggregation effects. These results suggest that the atisine-type alkaloids isolated from S. japonica are a class of novel antiplatelet aggregation agents.

Chiral ligands derived from abrine. 1. Synthesis of sec- and tert-β-amino alcohols and catalysis for enantioselective addition of diethylzinc toward aromatic aldehydes

A number of indole-containing chiral beta-amino alcohols 3a-d and 9a-e have been synthesized from the alkaloid, Abrine (1) readily available from seeds of Abrus precatorius collected in Yunnan Province of China Catalysis of the synthesized chiral ligands for the addition of diethylzinc toward benzaldehyde was examined. A significant role of the substituent(s) in the catalyst on the degree of asymmetric induction was uncovered. Enantiomeric excess of the product up to 94.2% was recorded.

Chiral ligands derived from Abrine .3. Asymmetric Pictet-Spengler reaction of Abrine methyl ester and synthesis of chiral 1,2,3,4-tetrahydro-beta-carbolines as promoters in addition of diethylzinc toward aromatic aldehydes

Asymmetric Pictet-Spengler reaction of a number of aldehydes with Abrine methyl ester (1) was performed at room temperature to furnish mainly 3 and high ee was obtained in enantioselective addition of Et(2)Zn with PhCHO catalyzed by chiral 1,2,3,4-tetrahydro-beta-carboline derivatives 5 synthesized from 3. Copyright (C) 1996 Elsevier Science Ltd

Cyclopeptides from the seeds of Annona glabra

A new cyclopeptide glabrin A has been isolated from the seeds of Annona glabra. Its structure was elucidated by 2D-NMR and FAB-MS.

Six New O-Terpenoidal Coumarins, Excavacoumarins B-G from Clausena excavata

Six new O-terpenoidal coumarins named excavacoumarins B-G (1-6) were isolated from the aerial part of Clausena excavata collected in Xishuangbanna, Yunnan.

Chiral ligands derived from abrine. Part 5: Substituent effects on asymmetric induction in enantioselective addition of diethylzinc to benzaldehyde catalyzed by chiral oxazolidines possessing an indole moiety

A number of the indole-containing chiral oxazolidines possessing the gem-di-p-tolyl and gem-di-o-tolyl groups at C-5 were synthesized from abrine and the effects of the C-5 and C-2 substituents on the asymmetric induction in catalytic enantioselective addition of diethylzinc to benzaldehyde were examined. A working model is proposed to rationalize the asymmetric catalysis by these chiral oxazolidines