Total synthesis of (±)-elegansidiol, (±)-farnesiferol B,and (±)-farnesiferol D

The racemic total synthesis of elegansidiol, farnesiferol B, and farnesiferol D has been obtained following a Diels–Alder approach. Gillman addition, cross metathesis reaction are the other key steps involved in the target synthesis.     

Simultaneous measurement of plasma vitamin D(3) metabolites, including 4β,25-dihydroxyvitamin D(3), using liquid chromatography-tandem mass spectrometry

Simultaneous and accurate measurement of circulating vitamin D metabolites is critical to studies of the metabolic regulation of vitamin D and its impact on health and disease. To that end, we have developed a specific liquid chromatography–tandem mass spectrometry (LC–MS/MS) method that permits the quantification of major circulating vitamin D₃ metabolites in human plasma. Plasma samples were subjected to a protein precipitation, liquid–liquid extraction, and Diels–Alder derivatization procedure prior to LC–MS/MS analysis. Importantly, in all human plasma samples tested, we identified a significant dihydroxyvitamin D₃ peak that could potentially interfere with the determination of 1α,25-dihydroxyvitamin D₃ [1α,25(OH)₂D₃] concentrations. This interfering metabolite has been identified as 4β,25-dihydroxyvitamin D₃ [4β,25(OH)₂D₃] and was found at concentrations comparable to 1α,25(OH)₂D₃. Quantification of 1α,25(OH)₂D₃ in plasma required complete chromatographic separation of 1α,25(OH)₂D₃ from 4β,25(OH)₂D₃. An assay incorporating this feature was used to simultaneously determine the plasma concentrations of 25OHD₃, 24R,25(OH)₂D₃, 1α,25(OH)₂D₃, and 4β,25(OH)₂D₃ in healthy individuals. The LC–MS/MS method developed and described here could result in considerable improvement in quantifying 1α,25(OH)₂D₃ as well as monitoring the newly identified circulating metabolite, 4β,25(OH)₂D₃.     

D—氨基酸在人体的来龙去脉：人体中D—氨基酸,D—氨基酸氧化酶,D…

本文分析近年,特别是近两年有关人体、食物中Ｄ－氨基酸、Ｄ－氨基酸氧化酶、Ｄ－天冬氨酸氧化酶研究进展,强调：１．必须研究食品中Ｄ－氨基酸水平;２．Ｄ－氨基酸氧化酶、Ｄ．天冬氨酸氧化酶作为药物治疗因Ｄ－氨基酸过量所致疾病。     

1α,25-Dihydroxyvitamin D(3) and its analog, 2-methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D(3) (2MD), suppress intraocular pressure in non-human primates

Ocular hypertension is the greatest known risk factor for glaucoma that affects an estimated 70 million people worldwide. Lowering intraocular pressure (IOP) remains the mainstay of therapy in the management of glaucoma. By means of microarray analysis, we have discovered that 1α,25-dihydroxyvitamin D(3) (1α,25-(OH)(2)D(3)) regulates genes that are known to be involved in the determination of intraocular pressure (IOP). Topical administration of 1α,25-(OH)(2)D(3) or its analog, 2-methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D(3) (2MD), markedly reduces IOP in non-human primates. The reduction in IOP is not the result of reduced aqueous humor formation, while a 35% increase in aqueous humor drainage by 1α,25-(OH)(2)D(3) was found but this increase did not achieve significance. Nevertheless, our results suggest that 1α,25-(OH)(2)D(3), or an analog thereof, may present a new approach to the treatment of glaucoma.     

Structure of ferrichrome-type siderophores with dissimilarN δ-acyl groups: Asperchrome B1,B2,3,D1, D2 and D3

Summary Asperchromes are a series of iron-chelating compounds which contain a cyclic hexapeptide backbone as in ferrichrome siderophores and differ from the latter in having heterogenous acyl groups in the ornithine side chains. The molecular structures of the asperchrome B and D series have been determined by¹H- and¹³C-NMR spectroscopy; single-crystal X-ray diffraction was used to determine the detailed structural features of asperchrome B₁ and asperchrome D₁. Asperchrome B₁ crystallizes in the triclinic space group P1 witha= 1.3143(5) nm,b=1.2200(5) nm,c=0.8949(3) nm,=105.17(4)°,=94.03(3)°, =109.65(3)°,V=1.2843 nm³,Z=1, _x =1.446 g cm^–3. FinalR=0.054 for 4625 reflections measured at 138 K using MoK. Asperchrome D₁ crystallizes in the monoclinic space group P2₁ witha=1.2248(11) nm,b=1.3795(9) nm,c=1.3644(6) nm,=93.24(6)°,V=2.3016 nm³,Z=2, _x =1.418 g cm^–3. FinalR=0.110 for 3180 reflections measured at 138 K using MoK radiation. The conformation of the molecular backbone and iron coordination geometry in both asperchrome B₁ and D₁ compare well with those observed in other known ferrichrome siderophores. The differences in the acyl groups are illustrated and the structural results are correlated with their iron transport properties.     

The 25(OH)D(3)/1alpha,25(OH)(2)D(3)-24R-hydroxylase: a catabolic or biosynthetic enzyme?

The kidney is the major source of the circulating dihydroxylated metabolites of vitamin D, 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] and 24R,25-dihydroxyvitamin D(3) [24R,25(OH)(2)D(3)]. The enzymes which catalyze the production of these two dihydroxylated vitamin D metabolites are the 25(OH)D(3)-1alpha-hydroxylase (1alpha-hydroxylase) and -24R-hydroxylase (24R-hydroxylase), respectively. While there is no controversy regarding the fundamental importance of the 1alpha-hydroxylase in the production of the steroid hormone 1alpha,25(OH)(2)D(3), the biologic significance of the 24R-hydroxylase has been the subject of ongoing discussion. Some hold that it is strictly catabolic, leading to side chain oxidation and cleavage of 25-hydroxylated vitamin D sterols, and others hold that it plays a biosynthetic role in the production of 24R,25(OH)(2)D(3) which has biologic activities distinct from those of 1alpha,25(OH)(2)D(3). The 24R-hydroxylase has properties in common with other multicatalytic steroidogenic enzymes: (1) the enzyme carries out multiple oxidative and carbon-carbon bond cleavages; (2) it utilizes two natural substrates; (3) its regulation varies depending on the cell or tissue in which it occurs. The purpose of this paper is to review the current literature relevant to the characteristics of the 24R-hydroxylase and its regulation in the context of other multicatalytic steroid hydroxylases in order to provide a perspective regarding its possible function as both a catabolic and activating enzyme in the vitamin D endocrine system.     

Clarification of the status of Rhipicephalus tricuspis Dönitz, 1906 and Rhipicephalus lunulatus Neumann, 1907 (Ixodoidea,Ixodidae)

The systematic status of Rhipicephalus species whose males have tricuspid adanal plates has been confused for many years. Some authors have regarded Rhipicephalus tricuspis Dönitz, 1906 as the only valid entity with this morphological character and synonymized both Rhipicephalus lunulatus Neumann, 1907 and Rhipicephalus glyphis Dönitz, 1910 with it. Others, however, have always maintained that R. tricuspis and R. lunulatus (syn. R. glyphis) are separate species. Detailed comparative studies, including scanning electron microscopy, of laboratory-reared series as well as numerous field collections of these ticks have now confirmed that the latter view is correct. In addition, a third species, designated here as a Rhipicephalus sp. near tricuspis, has been identified as a member of this group.All stages of R. tricuspis and R. lunulatus are herein redescribed and illustrated by means of scanning electron micrographs. Their life cycles in the laboratory, hosts, distribution and disease relationships are discussed and their differentiation is described with the aid of line drawings. Rhipicephalus tricuspis has been recorded primarily in southern Africa, but also in Zambia and western Zaire, in various types of dry woodland. Its adults are most commonly parasitic on relatively small mammals such as hares, spring hares, jackals and small antelopes. R. lunulatus is much more widespread in the Afrotropical region, most commonly in different types of woodland but also in a variety of other habitats. Its adults parasitize a very wide range of hosts including domestic animals (especially cattle and dogs), the African buffalo, many different antelopes (especially the larger species) and wild pigs. The Rhipicephalus sp. near tricuspis occurs in eastern and parts of central Africa, where its distribution often overlaps with that of R. lunulatus.     

相思子根化学成分研究——相思子醌A,B,D,E,F,G

从民间药用抗肝炎药相思子（ＡｂｒｕｓｐｒｅｃａｔｏｒｉｕｓＬ．）根中分得８个异黄烷醌类化合物,即相思子醌Ａ、Ｂ、Ｄ、Ｅ、Ｆ、Ｇ以及已知化合物３,７二羟基６甲氧基双氢黄酮和２,８二羟基３,４,９,１０四甲氧基紫檀素。用化学转化和光谱学方法包括１Ｈ１ＨＣＯＳＹ、１Ｈ１３ＣＣＯＳＹ、ＣＤ等方法鉴定它们的结构。     

多巴胺D3受体(D3R)的神经科学新进展

多巴胺(DA)是脑内一种重要的神经递质,通过不同DA受体亚型调控运动功能、认知活动和药物成瘾等生理、病理过程。多巴胺D3受体(D3R)属于D2样受体,但其功能长期不明。近年来,人们对它在神经科学中的意义有了新的认识。首先,D3R的信号通路独特,它被激活后显示细胞增殖效应,但cAMP信号传导途径不明显。其次,D3R基因敲除小鼠研究提示,正常生理状态下D3R仅表现辅助功能：在特定病理条件下,D3R显示出重要的“平衡缓冲作用”,在精神分裂症、帕金森病(PD)治疗中运动障碍副作用LID的发生和毒品复吸等病理过程扮演了重要角色。因此,D3R是一个重要的药物靶标。D3R拮抗剂在精神分裂症治疗中显示了临床前景,D3R激动剂则对PD治疗和毒品复吸防治展示了应用价值。