Progress in the Total Synthesis of Antitumor Tetrahydroisoquinoline Alkaloids

Among the tetrahydroisoquinoline(THIQ) of natural products, a family of THIQ alkaloids has the characteristics of similar biosynthetic pathway. Such THIQ alkaloids family mainly include Renieramycins, Ecteinasicdins, Tetrazaomine, Lemonomycin, etc. Most of these natural compounds have strong antitumor activities, and its family member Ecteinasicdins743 (ET-743, Trabectedin) has been marketed in the European Union and the United States for the treatment of advanced soft tissue tumors and ovarian cancer. Because of the excellent biological activity and complex chemical structure of this kind of THIQ products, it has aroused great interest of biologists and chemists, and many synthetic chemists have paid considerable efforts to their total synthesis over the past decade. Based on this, the recent advances in the total synthesis of such THIQ alkaloids are reviewed.     

短距乌头根的两个新二萜生物碱

从短距乌头（Ａｃｏｎｉｔｕｍ ｂｒｅｖｉｃａｌｃａｒａｔｕｍ Ｄｉｅｌｓ）的根分离到两个新的二萜生物碱：短距乌碱丁（ａｃｏｂｒｅｔｉｎｅ Ｄ, Ⅰ）和短距乌碱戊（ａｃｏｂｒｅｔｉｎｅ Ｅ, Ⅱ）,通过光谱技术（ＩＲ, ＭＳ, １Ｈ 和１３Ｃ－ＮＭＲ）和化学方法确定了它们的结构。短距乌碱丁最初以盐酸盐的形式分得,利用１Ｈ－１ＨＣＯＳＹ 和１３Ｃ－１Ｈ ＣＯＳＹ 归属了其盐的各碳和氢的化学位移值     

Origin of nitrogen in the biosynthesis of solanidine by Veratrum grandiflorum

Veratrum plants accumulate verazine as the major alkaloid in the rhizome during the dormant stage 4 months after cold treatment. The quantitative c     

Effect of the nitrogen form used in the growth medium (NO3 −, NH4 +) on alkaloid production in Datura stramonium L.

Plants of Datura stramonium var. tatula L. Torr. were cultivated on vermiculite and received two different mineral solutions. In one treatment only NO₃ ^–-nitrogen was added, while in the other NO₃ ^–-nitrogen was partly (20%) replaced by NH₄ ⁺-nitrogen. Total dose of nitrogen as well as interionic ratios were kept constant in both treatments. With the combined treatment (NO₃ ^–-NH₄ ⁺) a significant higher hyoscyamine content was found at the time when highest biomass was reached. This was apparently the result of an increased alkaloid biosynthesis. Also scopolamine content was positively influenced, but only at a point past maximal biomass yield.No significant differences in amounts of nitrogen bound per plant were found between both treatments.The higher alkaloid content observed with the combined treatment was associated with a higher relative proportion of bound nitrogen present in the alkaloids. It seems that more nitrogen is available for secondary metabolism when NH₄ ⁺-nitrogen is present in the culture medium.     

Effect of 2-chloroethylphosphonic acid on capsule formation and alkaloid content in Papaver somniferum

Application of different concentrations of ethephon (2-chloroethylphosphonic acid) to Papaver somniferum L. at the times of stem elongation, bud, and capsule formation produced different effects. Ethephon (10^-2 M ) retarded growth of the plant and inhibited capsule formation during stem elongation, significantly reduced capsule size during the flowering period, but did not alter capsule development during capsule formation. When applied during the period of stem elongation, ethephon (10^-3 M and 10^-4 M ) reduced capsule size; alkaloid accumulation was reduced by ethephon at a concentration of 10^-3 M , but slightly increased by 10^-4 M . Ethephon (10^-3 M and 10^-4 M ) did not alter capsule development or alkaloid content significantly when applied during bud formation, but stimulated capsule size and alkaloid content when applied during capsule formation. Pretreating the plants with Ag⁺ (silver nitrate) did not reverse the ethephon effect. The results suggest that capsule maturation and alkaloid accumulation in P. somniferum are modified by ethylene, which is produced as a result of exogenous ethephon treatment.     

Lupin alkaloids from Echinosophora koreensis

The nine known lupin alkaloids, (?)-cytisine, (?)-N-methylcytisine, (?)-N-(?3-oxobutyl)-cytisine, (?)-N-formylcytisine, (?)-rho     

Enzymatic synthesis of quinolizidine alkaloid esters: a tigloyl-CoA: 13-hydroxylupanine O-tigloyltransferase from Lupinus albus L.

A tigloyl-CoA: 13-hydroxylupanine O-tigloyl-transferase could be demonstrated in crude enzyme preparations from Lupinus albus seedlings. The enzyme activity increases concomitantly with for formation of 13-tigloyloxylupanine in developing lupin seedlings. The transferase catalyzes specifically the transfer of an acyl group to 13-hydroxylupanine. The apparent Km-values are 140 M for tigloyl-CoA and 18 M for 13-hydroxylupanine. Other hydroxylated compounds, e.g., lupinine, 4-hydroxylupanine, and cholesterol are not acylated. The transferase shows optimal activity at pH 7–8 and at 30°C. It is activated by dithioerythritol and inhibited by thiol reagents. Tigloyl-CoA can be replaced as acyl donor by benzoyl-CoA and to a lesser extent by valeroyl-CoA, 3-methylbutyryl-CoA, butyryl CoA and propionyl-CoA but not acetyl-CoA. Preliminary evidence indicates that the transfer of the tigloyl and benzoyl moieties is catalyzed by different enzymes. The transferase activity could only be demonstrated in plants which produce quinolizidine alkaloids.Abbreviations DIECA diethyldithiocarbamate - DTE dithioerythritol - GLC gas-liquid chromatography     

Studies on the Chemical Constituents of Gnetum montanum Markg

Six compounds had been isolated from the stem of Gnetum montanum Markgr, on the basis of spectral analysis (UV, IR, 1H NMR, 13C NMR and MS), physico-chemical constants and preparation of the derivative. They were identified as 2-hydroxy-3-methoxyl-4-methoxycarbonyl pyrrole (1), 2-hydroxy-3-methoxymethyl-4-methoxycarbonyl pyrrole (2), 3,4′-dihydroxy-4-methoxy-dibenzyl ether (3), 3, 3′,4′-trihydroxy-4-methoxy-dibenzy ether (4), 2,3-diphenyl-pyrrole (5) and aminemethyl-methyl alcohol (6). (1)—(4) are new compounds,