Methods that may be used for the manufacture of a class of chemical compounds known as terpenoid indole alkaloids, including tabersonine and catharanthine are provided. Compositions useful for the synthesis of terpenoid indole alkaloids, including tabersonine and catharanthine are also provided. The provided compounds are useful in the manufacture of chemotherapeutic agents.

The present invention discloses an improved process for the extraction of alpha yohimbine from leaves of Rauwolfia species, preferably Rauwolfia canescens/Rauwolfia tetraphylla. Process involves use of non-polar alcoholic solvent e.g. methanol for precipitating the compound of interest, repetitive washing with halogenated solvents and washing with hexane or petroleum ether to obtain high yields of high purity extract. Use of organic acids such as tartaric acid, acetic acid and organic solvent ethyl acetate etc. is eliminated making the process less time consuming and economical. The yield of the final product is 50-60% higher i.e. 600-670 mg/100 g dry leaves, than prior art process. Further, the extract obtained by the process of present invention contains yohimbine hydrochloride as a marker compound in analytically detectable amounts of more than 0.1% of the extract.

Present invention discloses a novel, commercially viable process for extraction of Alpha yohimbine from the bark, stem and leaves of Rauwolfia species. The extract is obtained by a precipitation method involving alternate steps of acidification and alkalization along with use of specific organic solvents. The extract gives higher yield of 7-8 fold as compared to other processes and without use of any column chromatography at all. Yield of alpha yohimbine from roots and leaves of Rauwolfia canescens by process of present invention was 0.017% and 0.4% respectively, indicating that leaves are a much better source. The HPLC analysis of the compound obtained indicated a purity of >90%.

Present invention discloses a novel, commercially viable process for extraction of Alpha yohimbine from the bark, stem and leaves of Rauwolfia species. The extract is obtained by a precipitation method involving alternate steps of acidification and alkalization along with use of specific organic solvents. The extract gives higher yield of 7-8 fold as compared to other processes and without use of any column chromatography at all. Yield of alpha yohimbine from roots and leaves of Rauwolfia canescens by process of present invention was 0.017% and 0.4% respectively, indicating that leaves are a much better source. The HPLC analysis of the compound obtained indicated a purity of >90%.

The present invention relates to phenyl [a]indole[2,3-g]quinolizine compounds represented by formula (I), a preparation method therefor, a pharmaceutical composition, and applications thereof. Specific applications are applications in the preparation of drugs for treating diseases related to a proprotein convertase subtilisin Kexin-9 (PCSK9), comprising the applications in the preparation of drugs for treating hyperlipemia, hypercholesterolemia, hypertriglyceridemia, fatty liver deformation, atherosclerosis, obesity and other metabolic diseases.

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The present invention relates to phenyl [a]indole[2,3-g]quinolizine compounds represented by formula (I), a preparation method therefor, a pharmaceutical composition, and applications thereof. Specific applications are applications in the preparation of drugs for treating diseases related to a proprotein convertase subtilisin Kexin-9 (PCSK9), comprising the applications in the preparation of drugs for treating hyperlipemia, hypercholesterolemia, hypertriglyceridemia, fatty liver deformation, atherosclerosis, obesity and other metabolic diseases.

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Embodiments of screening methods for determining test agents effective for modifying the appearance of pigmented skin are provided. The screening method may comprise the steps of contacting a cell, a cell culture, or bulk cells with the test agent, wherein the cell, the cell culture, or the bulk cells comprise ADR1 receptors, and determining based on the binding interaction of the test agent with the ADR1 receptors whether the test agent is an effective ADR1 receptor antagonist suitable for modifying the appearance of pigmented skin, wherein a test agent is considered to be an effective ADR1 receptor antagonist when it defines a half maximal inhibitory concentration of less than about 1000 ppm.

The present invention relates to novel antitumor agents and pharmaceutically acceptable salts thereof, processes and intermediates for the manufacture of these novel constrained cyclic frameworks of general formula I and II, and medicaments containing such compounds.

The present invention relates to novel antitumor agents and pharmaceutically acceptable salts thereof, processes and intermediates for the manufacture of these novel constrained cyclic frameworks of general formula I and II, and medicaments containing such compounds.