126640-98-0Relevant articles and documents
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.
, p. 3339 - 3349 (2010)
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)
(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.
Stereospecific, Enantiospecific Total Synthesis of the Sarpagine Indole Alkaloids (E)16-Epiaffinisine, (E)16-Epinormacusine B, and Dehydro-16-epiaffinisine
Yu, Jianming,Liao, Xuebin,Cook, James M.
, p. 4681 - 4684 (2002)
(Matrix Presented) The first stereospecific total synthesis of the sarpagine indole alkaloids (E)16-epiaffinisine (1), (E)16-epinormacusine B (2), and dehydro-16-epiaffinisine (4) has been completed; this method has also resulted in the synthesis of dehydro-16-epinormacusine B (5). The formation of the required ether in both 4 and 5 was realized with complete control from the top face on treatment of the corresponding alcohols with DDQ/THF in 98% and 95% yields, respectively.
Asymmetric Total Synthesis of Sarpagine-Related Indole Alkaloids Hydroxygardnerine, Hydroxygardnutine, Gardnerine, (E)-16-epi-Normacusine B, and Koumine
Kitajima, Mariko,Watanabe, Keisuke,Maeda, Hiroyuki,Kogure, Noriyuki,Takayama, Hiromitsu
supporting information, p. 1912 - 1915 (2016/05/19)
Sarpagine-related indole alkaloids (-)-hydroxygardnerine, (+)-hydroxygardnutine, (-)-gardnerine, (+)-(E)-16-epi-normacusine B, and (-)-koumine were divergently synthesized via a common intermediate possessing a piperidine ring with an exocyclic (E)-ethylidene side chain, which was constructed by a gold(I)-catalyzed 6-exo-dig cyclization strategy.
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.
The first enantiospecific total synthesis of the 3-oxygenated sarpagine indole alkaloids affinine and 16-epiaffinine, as well as vobasinediol and 16-epivobasinediol
Yang, Jie,Rallapalli, Sundari K.,Cook, James M.
scheme or table, p. 815 - 817 (2010/03/26)
The first enantiospecific total synthesis of the 3-oxygenated sarpagine indole alkaloids affinine (1) and 16-epiaffinine (2) as well as the synthesis of vobasinediol (3) and 16-epivobasinediol (4) was accomplished from d-(+)-tryptophan methyl ester.
General approach for the synthesis of 12-methoxy-substituted sarpagine indole alkaloids including (-)-12-methoxy-Nb-methylvoachalotine, (+)-12-methoxy-Na-methylvellosimine, (+)-12-methoxyaffinisine, and (-)-fuchsiaefoline
Zhou, Hao,Liao, Xuebin,Yin, Wenyuan,Ma, Jun,Cook, James M.
, p. 251 - 259 (2007/10/03)
The enantiospecific synthesis of 7-methoxy-D-tryptophan ethyl ester was completed by combination of the Larock heteroannulation process with a Schoellkopf-based chiral auxiliary in good yield. This ester was then employed in the first regiospecific, stere
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.
General approach for the total synthesis of the sarpagine related indole alkaloids (+)-Na-methyl-16-epipericyclivine, (-)-alkaloid Q3 and (-)-panarine via the asymmetric Pictet-Spengler reaction
Yu, Jianming,Wearing, Xiangyu Z.,Cook, James M.
, p. 543 - 547 (2007/10/03)
The stereospecific total synthesis of (+)-Na-methyl-16-epipericyclivine (1) 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
Deoxysarpagine hydroxylase--a novel enzyme closing a short side pathway of alkaloid biosynthesis in Rauvolfia.
Yu, Bingwu,Ruppert, Martin,Stoeckigt, Joachim
, p. 2479 - 2483 (2007/10/03)
Microsomal preparations from cell suspension cultures of the Indian plant Rauvolfia serpentina catalyze the hydroxylation of deoxysarpagine under formation of sarpagine. The newly discovered enzyme is dependent on NADPH and oxygen. It can be inhibited by typical cytochrome P450 inhibitors such as cytochrome c, ketoconazole, metyrapone, tetcyclacis and carbon monoxide. The CO-effect is reversible with light (450 nm). The data indicate that deoxysarpagine hydroxylase is a novel cytochrome P450-dependent monooxygenase. A pH optimum of 8.0 and a temperature optimum of 35 degrees C were determined. K(m) values were 25 microM for NADPH and 7.4 microM for deoxysarpagine. Deoxysarpagine hydroxylase activity was stable in presence of 20% sucrose at -25 degrees C for >3 months. The analysis of presence of the hydroxylase in nine cell cultures of seven different families indicates a very limited taxonomic distribution of this enzyme.
