6874-98-2Relevant academic research and scientific papers
General approach for the synthesis of sarpagine/ajmaline indole alkaloids. Stereospecific total synthesis of the sarpagine alkaloid (+)-vellosimine
Wang, Tao,Cook, James M.
, p. 2057 - 2059 (2000)
matrix presented (+)-Vellosimine has been synthesized enantiospecifically in 27% overall yield from commercially available D-(+)-tryptophan methyl ester via the asymmetric Pictet-Spengler reaction and a stereocontrolled intramolecular palladium-coupling reaction as key steps.
Enantioselective, protecting-group-free total synthesis of sarpagine alkaloids-A generalized approach
Krüger, Sebastian,Gaich, Tanja
, p. 315 - 317 (2015/09/21)
A generalized synthetic access to sarpagine alkaloids through a joint synthetic sequence has been accomplished. Its applicability is showcased by the enantioselective total syntheses of vellosimine (1), N-methylvellosimine (3 ), and 10-methoxyvellosimine (8). The synthetic sequence is concise (eight steps) from known compound 13, and requires no protecting groups. The indole heterocycle was introduced in the last step. This strategy allows access to sarpagine alkaloids through a shared synthetic route leading to precursor 10, which we term "privileged intermediate". Starting from this intermediate, all sarpagine alkaloids can be synthesized using phenylhydrazines with different substitution patterns (15-17). Our approach brings about the advantage, that synthesis optimization only needs to be performed once for many natural products. The key features of the synthesis are a [5+2]-cycloaddition and a ring enlargement.
Stereospecific total synthesis of the indole alkaloid ervincidine. Establishment of the C-6 hydroxyl stereochemistry
Rallapalli, Sundari K.,Namjoshi, Ojas A.,Tiruveedhula, V. V. N. Phani Babu,Deschamps, Jeffrey R.,Cook, James M.
supporting information, p. 3776 - 3780 (2014/05/20)
The total synthesis of the indole alkaloid ervincidine (3) is reported. This research provides a general entry into C-6 hydroxy-substituted indole alkaloids with either an α or a β configuration. This study corrects the errors in Glasby's book (Glasby, J. S. Encyclopedia of the Alkaloids; Plenum Press: New York, 1975) and Lounasmaa et al.'s review (Lounasmaa, M.; Hanhinen, P.; Westersund, M. In The Alkaloids; Cordell, G. A., Ed.; Academic Press: San Diego, CA, 1999; Vol. 52, pp 103-195) as well as clarifies the work of Yunusov et al. (Malikov, V. M.; Sharipov, M. R.; Yunusov, S. Yu. Khim. Prir. Soedin. 1972, 8, 760-761. Rakhimov, D. A.; Sharipov, M. R.; Aripov, Kh. N.; Malikov, V. M.; Shakirov, T. T.; Yunusov, S. Yu. Khim. Prir. Soedin. 1970, 6, 724-725). It establishes the correct absolute configuration of the C-6 hydroxyl function in ervincidine. This serves as a structure proof and corrects the misassigned structure reported in the literature.
Enantiospecific total synthesis of the important biogenetic intermediates along the ajmaline pathway, (+)-polyneuridine and (+)-polyneuridine aldehyde, as well as 16-epivellosimine and Macusine A
Yin, Wenyuan,Kabir, M. Shahjahan,Wang, Zhijian,Rallapalli, Sundari K.,Ma, Jun,Cook, James M.
scheme or table, p. 3339 - 3349 (2010/07/13)
The first stereospecific synthesis of polyneuridine aldehyde (6), 16-epivellosimine (7), (+)-polyneuridine (8), and (+)-macusine A (9) has been accomplished from commercially available d-(+)-tryptophan methyl ester. d-(+)-Tryptophan has served here both as the chiral auxiliary and the starting material for the synthesis of the common intermediate, (+)-vellosimine (13). This alkaloid was available in enantiospecific fashion in seven reaction vessels in 27% overall yield from d-(+)-trytophan methyl ester (14) via a combination of the asymmetric Pictet-Spengler reaction, Dieckmann cyclization, and a stereocontrolled intramolecular enolate-driven palladium-mediated cross-coupling reaction. A new process for this stereocontrolled intramolecular cross-coupling has been developed via a copper-mediated process. The initial results of this investigation indicated that an enolate-driven palladium-mediated cross-coupling reaction can be accomplished by a copper-mediated process which is less expensive and much easier to work up. An enantiospecific total synthesis of (+)-polyneuridine aldehyde (6), which has been proposed as an important biogenetic intermediate in the biosynthesis of quebrachidine (2), was then accomplished in an overall yield of 14.1% in 13 reaction vessels from d-(+)-tryptophan methyl ester (14). Aldehyde 13 was protected as the N a-Boc aldehyde 32 and then converted into the prochiral C(16)-quaternary diol 12 via the practical Tollens reaction and deprotection. The DDQ-mediated oxidative cyclization and TFA/Et3SiH reductive cleavage served as protection/deprotection steps to provide a versatile entry into the three alkaloids polyneuridine aldehyde (6), polyneuridine (8), and macusine A (9) from the quarternary diol 12. The oxidation of the 16-hydroxymethyl group present in the axial position was achieved with the Corey-Kim reagent to provide the desired β-axial aldehydes, polyneuridine aldehyde (6), and 16-epivellosimine (7) with 100% diastereoselectivity.
First enantiospecific total synthesis of the important biogenetic intermediates, (+)-polyneuridme and (+)-polyneuridine aldehyde, as well as 16-epi-vellosimine and macusine A
Yin, Wenyuan,Jun, Ma.,Rivas, Felix M.,Cook, James M.
, p. 295 - 298 (2007/10/03)
(Chemical Equation Presented) The first enantiospecific total synthesis of the alkaloids 16-epi-vellosimine (1), (+)-polyneuridine (2), (+)-polyneuridine aldehyde (3), and macusine A (4) is reported. The key oxidation was accomplished with the Corey-Kim reagent to provide the important biogenetic intermediates, 16-epi-vellosimine (1) and polyneuridine aldehyde (3), the latter of which is required for the conversion of the sarpagan skeleton into the ajmalan system in the biosynthesis of quebrachidine.
General approach for the synthesis of sarpagine indole alkaloids. Enantiospecific total synthesis of (+)-vellosimine, (+)-normacusine B, (-)-alkaloid Q3, (-)-panarine, (+)-Na-methylvellosimine, and (+)-Na-methyl-16-epipericyclivine
Yu, Jianming,Wang, Tao,Liu, Xiaoxiang,Deschamps, Jeffrey,Flippen-Anderson, Judith,Liao, Xuebin,Cook, James M.
, p. 7565 - 7581 (2007/10/03)
The first total synthesis of (+)-Na-methyl-16-epipericyclivine (9) was completed [from D-(+)-tryptophan methyl ester] in an overall yield of 42% (eight reaction vessels). The optical rotation [[α]D +22.8 (c 0.50, CHCl3)] obtained on this material confirmed that the reported optical rotation [[α]D 0 (c 0.50, CHCl 3)]47 was biogenetically unreasonable. The total syntheses of (+)-vellosimine, (+)-normacusine B, (-)-alkaloid Q3, (-)-panarine, and (+)-Na-methylvellosimine are also described. Moreover, a mixed sample (1:1) of synthetic (-)-panarine and natural (-)-panarine yielded only one set of signals in the 13C NMR; this indicated that the two compounds are identical and further confirmed the correct configuration of (+)-vellosimine, (+)-normacusine B, and (-)-alkaloid Q3. In this approach, the key templates, (-)-Na-H,N b-benzyltetracyclic ketone 15a and (-)-Na-methyl,N b-benzyltetracyclic ketone 43 were synthesized on multihundred gram scale by the asymmetric Pictet-Spengler reaction and a stereocontrolled Dieckmann cyclization via improved sequences. An intramolecular palladium (enolate-mediated) coupling reaction was employed to introduce the C(19)-C(20) E-ethylidene function in the sarpagine alkaloids for the first time in stereospecific fashion.
Stereoselective Transformation of Ajmaline into Three Minor Gelsemium Alkaloids, Koumidine, (19Z)-Anhydrovobasinediol and N-Demethoxyrankinidine and their Absolute Configuration
Kitajima, Mariko,Takayama, Hiromitsu,Sakai, Shin-ichiro
, p. 1773 - 1779 (2007/10/02)
Ajmaline was converted into new Gelsemium alkaloids, 19Z-anhydrovobasinediol and N-demethoxyrankinidine, via koumidine along the biomimetic sequence, and the absolute configuration of these alkaloids was determined by these transformations.
Studies on Apocynaceae: Hemi-Synthesis of Vellosimine from Rhazine - Application of HOMCOR (COSY)-2D NMR Spectroscopy in Structure Eludication of Ajmaline-Sarpagine Skeleton
Banerji, J.,Das, B.,Chakrabarti, R.,Shoolery, J. N.
, p. 709 - 711 (2007/10/02)
The rare indole alkaloid vellosimine (1) has been isolated from Rauwolfia reflexa Teism and Binn.The occurrence of this indolic base has been observed for the first time in R. reflexa.The hemi-synthesis of this compound from rhazine has been achieved.The study of the HOMCOR (COSY)-2D NMR spectroscopy of vellosimine provides important information on structure of the alkaloids having ajmaline-sarpagine skeleton.
Polyneuridine Aldehyde Esterase: an Unusually Specific Enzyme involved in the Biosynthesis of Sarpagine Type Alkaloids
Pfitzner, Artur,Stoeckigt, Joachim
, p. 459 - 460 (2007/10/02)
Polyneuridine aldehyde esterase is a highly substrate specific enzyme which catalyses the conversion of the monoterpenoid C10-unit into C9-unit at the stage of polyneuridine aldehyde in the biosynthesis of sarpagine type alkaloids.
Biogenetic link between sarpagine and ajmaline type alkaloids
Pfitzner,Stockigt
, p. 5197 - 5200 (2007/10/02)
A new enzyme - vinocrine synthase - isolated from cell suspension cultures of Rauwolfia serpentina, links sarpagine and ajmaline alkaloids by catalyzing the acetyl-coenzyme-A dependent biosynthesis of the ajmalan skeleton from sarpagan type compounds.
