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James M Cook - One of the best experts on this subject based on the ideXlab platform.
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the stereospecific and enantiospecific synthesis of indole alkaloids which culminated in the ambidextrous pictet spengler reaction for the c 19 methyl substituted Sarpagine family
2021Co-Authors: Toufiqur M Rahman, Ojas A. Namjoshi, James M CookAbstract:Abstract The Pictet-Spengler reaction continues to be widely employed in the synthesis of bioactive natural products, as well as synthetic compounds containing the THβC and THIQ moieties. The asymmetric version of this reaction has been central to the enantiospecific total synthesis of >150 Sarpagine/macroline/ajmaline alkaloids. The diastereospecific Pictet-Spengler reaction under thermodynamic control is crucial to the large-scale synthesis of the important tetracyclic bicyclo[3.3.1] core in >98% ee towards many indole alkaloids from this superfamily. Extensive exploration of the Pictet-Spengler reaction for the emerging class of C-19 methyl-substituted Sarpagine/macroline/ajmaline alkaloids has resulted in the ambidextrous version, which has enabled access to both the natural and unnatural enantiomers of alkaloids starting with either D- or L-tryptophan, at will. Some noteworthy recent applications of the large scale Pictet-Spengler reaction in the total synthesis of Sarpagine-related alkaloids and the development of the ambidextrous Pictet-Spengler reaction are described in this chapter.
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The stereospecific and enantiospecific synthesis of indole alkaloids which culminated in the ambidextrous Pictet–Spengler reaction for the C-19 methyl–substituted Sarpagine family
Progress in Heterocyclic Chemistry, 2021Co-Authors: M. Toufiqur Rahman, Ojas A. Namjoshi, James M CookAbstract:Abstract The Pictet-Spengler reaction continues to be widely employed in the synthesis of bioactive natural products, as well as synthetic compounds containing the THβC and THIQ moieties. The asymmetric version of this reaction has been central to the enantiospecific total synthesis of >150 Sarpagine/macroline/ajmaline alkaloids. The diastereospecific Pictet-Spengler reaction under thermodynamic control is crucial to the large-scale synthesis of the important tetracyclic bicyclo[3.3.1] core in >98% ee towards many indole alkaloids from this superfamily. Extensive exploration of the Pictet-Spengler reaction for the emerging class of C-19 methyl-substituted Sarpagine/macroline/ajmaline alkaloids has resulted in the ambidextrous version, which has enabled access to both the natural and unnatural enantiomers of alkaloids starting with either D- or L-tryptophan, at will. Some noteworthy recent applications of the large scale Pictet-Spengler reaction in the total synthesis of Sarpagine-related alkaloids and the development of the ambidextrous Pictet-Spengler reaction are described in this chapter.
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the c 19 methyl substituted Sarpagine macroline ajmaline alkaloids diversity occurrence bioactivity and synthesis
2020Co-Authors: Toufiqur M Rahman, James M CookAbstract:Abstract The C-19 methyl substituted Sarpagine/macroline/ajmaline alkaloids are an emerging group of structurally and biosynthetically related alkaloids. To date, there are more than 70 alkaloids that can be categorized as belonging to this subgroup. About two dozen of these alkaloids have been reported to possess useful and important bioactivity ranging from anti-inflammatory to anticancer, while the rest of the alkaloids remain mostly unexplored. The total synthesis of more than a dozen of these alkaloids has been reported, to date. This chapter is a compilation of the monomeric alkaloids which possess the C-19 methyl substituent (as a part of the core ring system), which belong to either the Sarpagine, macroline, or ajmaline alkaloid series reported recently. An up-to-date discussion of their isolation from various plant sources (and corresponding plant morphology), proposed biosynthetic studies, as well as reported biosynthesis are included. In addition, the partial or formal, as well as the total syntheses have also been included.
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Total Synthesis of Sarpagine-Related Bioactive Indole Alkaloids.
Chemistry (Weinheim an der Bergstrasse Germany), 2018Co-Authors: M. Toufiqur Rahman, Jeffrey R. Deschamps, Gregory H. Imler, James M CookAbstract:Extension of the asymmetric Pictet-Spengler reaction to bulkier Nb -alkylated tryptophan derivatives resulted in an improved stereospecific access to the key bicyclo[3.3.1]nonane core of bioactive C-19 methyl substituted Sarpagine/macroline/ajmaline indole alkaloids with excellent diastereoselectivity by internal asymmetric induction. Complete stereocontrol of the C-19 methyl function in either the α- or β-configuration was achieved, which enables the total synthesis of any member from this group of thirty alkaloids. We report herein, the total synthesis of macrocarpines (A-C) 1-3, talcarpine 4, N(4)-methyl-N(4),21-secotalpinine 5, dihydroperaksine 8 and deoxyperaksine 9.
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Concise Total Synthesis of (−)‐Affinisine Oxindole, (+)‐Isoalstonisine, (+)‐Alstofoline, (−)‐Macrogentine, (+)‐Na‐Demethylalstonisine, (−)‐Alstonoxine A, and (+)‐Alstonisine
Chemistry (Weinheim an der Bergstrasse Germany), 2017Co-Authors: Michael Rajesh Stephen, M. Toufiqur Rahman, Veera Venkata Naga Phani Babu Tiruveedhula, Jeffrey R. Deschamps, German O. Fonseca, James M CookAbstract:A highly enantio- and diastereoselective strategy to access any member of the Sarpagine/macroline family of oxindole alkaloids via internal asymmetric induction was developed from readily available d-(+)-tryptophan. At the center of this approach was the diastereospecific generation of the spiro[pyrrolidine-3,3′-oxindole] moiety at an early stage via a tert-butyl hypochlorite-promoted oxidative rearrangement of a chiral tetrahydro-β-carboline derivative. This key branching point determined the spatial configuration at the C-7 spiro center to be entirely 7R or 7S. Other key stereospecific processes were the asymmetric Pictet–Spengler reaction and Dieckmann cyclization, which were scalable to the 600 and 150 gram levels, respectively. Execution of this approach resulted in first enantiospecific total synthesis of (+)-isoalstonisine and (−)-macrogentine from the chitosenine series (7R), as well as (+)-alstonisine, (+)-alstofoline, (−)-alstonoxine A and (+)-Na-demethylalstonisine from the alstonisine series (7S).
Tao Wang - One of the best experts on this subject based on the ideXlab platform.
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The Enantiospecific, Stereospecific Total Synthesis of the Ring-A Oxygenated Sarpagine Indole Alkaloids (+)-Majvinine, (+)-10-Methoxyaffinisine, and (+)-Na-MethylSarpagine, as Well as the Total Synthesis of the Alstonia Bisindole Alkaloid Macralstoni
The Journal of organic chemistry, 2003Co-Authors: Shuo Zhao, Xuebin Liao, Tao Wang, Judith L. Flippen-anderson, James M CookAbstract:The first stereospecific, enantiospecific total synthesis of the ring-A oxygenated Sarpagine indole alkaloids (+)-Na-methylSarpagine (8), (+)-majvinine (14), and (+)-10-methoxyaffinisine (49), as well as the first total synthesis of the Alstonia bisindole alkaloid macralstonidine (9), has been accomplished. This approach employed the Schollkopf chiral auxiliary for the stereospecific construction of the desired d-(+)-tryptophan unit required for the asymmetric Pictet−Spengler reaction. In addition, the strategy was doubly convergent for the enolate-mediated Pd0 coupling process and the asymmetric Pictet−Spengler reaction can be employed to synthesize both macroline (2) and Na-methylSarpagine (8), the coupling of which provides macralstonidine (9). This approach to ring-A substituted alkoxyindole alkaloids should find wide application for the synthesis of other alkaloids for it is stereospecific and either enantiomer can be prepared with ease.
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Enantiospecific total synthesis of (-)-(E)16-epiaffinisine, (+)-(E)16-epinormacusine B, and (+)-dehydro-16-epiaffinisine as well as the stereocontrolled total synthesis of alkaloid G.
The Journal of organic chemistry, 2003Co-Authors: Tao Wang, Xiangyu Z. Wearing, James M CookAbstract:An efficient strategy is described for the total synthesis of the Sarpagine-related indole alkaloids (−)-(E)16-epiaffinisine (1), (+)-(E)16-epinormacusine B (2), and (+)-dehydro-16-epiaffinisine (4). A key step employed the chemospecific and regiospecific hydroboration/oxidation at C(16)−C(17); this method has also resulted in the synthesis of (+)-dehydro-16-epinormacusine B (5). The oxy-anion Cope rearrangement followed by protonation of the enolate that resulted under conditions of kinetic control has been employed to generate the key asymmetric centers at C(15), C(16), and C(20) in alkaloid G (7) in a highly stereocontrolled fashion (>43:1). Conditions that favor control of the Sarpagine stereochemistry at C(16) vs the epimeric ajmaline configuration at the same stereocenter have been determined. The formation of the required cyclic ether in 4, 5, and 7 was realized with complete control from the top face on treatment of the corresponding alcohols with DDQ/THF or DDQ/aq THF in excellent yields.
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the enantiospecific stereospecific total synthesis of the ring a oxygenated Sarpagine indole alkaloids majvinine 10 methoxyaffinisine and na methylSarpagine as well as the total synthesis of the alstonia bisindole alkaloid macralstonidine
Journal of Organic Chemistry, 2003Co-Authors: Shuo Zhao, Xuebin Liao, Tao Wang, Judith L Flippenanderson, James M CookAbstract:The first stereospecific, enantiospecific total synthesis of the ring-A oxygenated Sarpagine indole alkaloids (+)-Na-methylSarpagine (8), (+)-majvinine (14), and (+)-10-methoxyaffinisine (49), as well as the first total synthesis of the Alstonia bisindole alkaloid macralstonidine (9), has been accomplished. This approach employed the Schollkopf chiral auxiliary for the stereospecific construction of the desired d-(+)-tryptophan unit required for the asymmetric Pictet−Spengler reaction. In addition, the strategy was doubly convergent for the enolate-mediated Pd0 coupling process and the asymmetric Pictet−Spengler reaction can be employed to synthesize both macroline (2) and Na-methylSarpagine (8), the coupling of which provides macralstonidine (9). This approach to ring-A substituted alkoxyindole alkaloids should find wide application for the synthesis of other alkaloids for it is stereospecific and either enantiomer can be prepared with ease.
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Enantiospecific total synthesis of the Sarpagine related indole alkaloids talpinine and talcarpine as well as the improved total synthesis of alstonerine and anhydromacrosalhine-methine via the asymmetric Pictet-Spengler reaction.
The Journal of organic chemistry, 2000Co-Authors: Tao Wang, James M CookAbstract:The enantiospecific total synthesis of talpinine 1 and talcarpine 2 has been accomplished from d-(+)-tryptophan in 13 steps (11 reaction vessels) in 10% and 9.5% overall yields, respectively. Moreover, this synthetic approach has been employed for the improved synthesis of alstonerine 3 and anhydromacrosalhine-methine 4 in 12% and 14% overall yield, respectively. A convenient synthetic route for the enantiospecific, stereospecific preparation of the key intermediate (−)-Na-H, Nb-benzyl tetracyclic ketone 15a via the asymmetric Pictet−Spengler reaction on a multihundred-gram scale has been developed. A diastereocontrolled (>30:1) anionic oxy-Cope rearrangement and the intramolecular rearrangement to form ring-E and an Nb-benzyl/Nb-methyl transfer reaction also served as key steps. This general approach can now be utilized for the synthesis of macroline/Sarpagine related indole alkaloids and their antipodes for biological screening.
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General Approach for the Synthesis of Ajmaline/Sarpagine Indole Alkaloids: Enantiospecific Total Synthesis of (+)-Ajmaline, Alkaloid G, and Norsuaveoline via the Asymmetric Pictet−Spengler Reaction
Journal of the American Chemical Society, 1999Co-Authors: Jin Li, Robert W Weber, D Soerens, Desiree S. Grubisha, Dennis W Bennett, Andrew C Peterson, Peng Yu, Tao Wang, James M CookAbstract:A general approach (oxyanion-Cope strategy) for the synthesis of Sarpagine/ajmaline indole alkaloids has been developed. (+)-Ajmaline 1 and alkaloid G 2 as well as norsuaveoline 3 have been synthesized from d-(+)-tryptophan in enantiospecific fashion via the asymmetric Pictet−Spengler reaction and a stereocontrolled oxyanion-Cope rearrangement as key steps. The synthesis of these indole alkaloids employed a stereospecific Pictet−Spengler/Dieckmann protocol to prepare the key intermediate, (−)-Nb-benzyl tetracyclic ketone (7a or 7b). This ketone was converted into α,β-unsaturated aldehyde (8a or 8b) and further transformed into (+)-ajmaline 1 and alkaloid G 2 as well as norsuaveoline 3. It was also found that reduction of 29 can be done stereospecifically to form the 2-epidiacetylajmaline derivative 30 which has the same configuration at C(2) as that of quebrachidine and of the bisindole alstonisidine. The ring closure reaction (from 27 to 28) to form the Sarpagine skeleton was completed in 91% yield. It s...
Hiromitsu Takayama - One of the best experts on this subject based on the ideXlab platform.
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Asymmetric Total Synthesis of Sarpagine-Related Indole Alkaloids Hydroxygardnerine, Hydroxygardnutine, Gardnerine, (E)-16-epi-Normacusine B, and Koumine
Organic letters, 2016Co-Authors: Mariko Kitajima, Keisuke Watanabe, Hiroyuki Maeda, Noriyuki Kogure, Hiromitsu TakayamaAbstract: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.
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Chapter 11 Monoterpenoid Indole Alkaloid Syntheses Utilizing Biomimetic Reactions
The Alkaloids: Chemistry and Biology, 1998Co-Authors: Hiromitsu Takayama, Shin-ichiro SakaiAbstract:Publisher Summary The chapter discusses monoterpenoid indole alkaloid syntheses utilizing biomimetic reactions and reviews the significant accomplishments concerning the biomimetic synthesis of secologanin-derived monoterpenoid indole alkaloids that have been reported in the past 10–15 years. This chapter consists of five areas of research in the field: (1) biomimetic syntheses of Corynanthe-related alkaloids from secologanin, strictosidine, and their analogues, (2) syntheses of Aspidosperma and Iboga alkaloids via secodine or dehydrosecodine intermediates, (3) biomimetic skeletal rearrangement and fragmentation, (4) biomimetic syntheses in the Sarpagine family, and ( 5 ) biomimetic bisindole alkaloid syntheses. The chapter describes many successful results concerning monoterpenoid indole alkaloid syntheses performed in recent decades by utilizing a biomimetic reaction in a synthetically crucial step. Adopting this biomimetic strategy, a number of structurally complex and/or unusual alkaloids are synthesized efficiently in a regio- and stereoselective manner. The biosynthesis by chemical means has led to the discovery of new synthetic methodology and reactions. In some cases, biogenetically patterned synthesis supported (or provided proof of) the postulated biosynthetic pathway.
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Chapter 1 Gelsemium Alkaloids
The Alkaloids: Chemistry and Pharmacology, 1997Co-Authors: Hiromitsu Takayama, Shin-ichiro SakaiAbstract:Publisher Summary This chapter reviews the chemistry and biological activity of the gelsemium alkaloids. It discusses that the number of Gelsemium alkaloids has increased dramatically, and the synthetic aspects of this field have progressed significantly. The chapter focuses on the structure elucidations and synthetic studies. In the tribe Gelsemiae, belonging to the family Loganiaceae, there are two genera: Mostueu and Gelsemium, the latter of which comprises three species. Gelsemium eleguns Benth, which is distributed over southeastern Asia, is known as a toxic plant and has been used in traditional Chinese medicine as a remedy for certain kinds of skin ulcers. Recent clinical experiments with Kou-Wen on malignant tumors such as hepatic cancer have given encouraging results, and analgesic activity for the palliation of various acute cancer pains with no addictive side effect has been reported. The chapter explores that the Gelsemium alkaloids are classified into five groups—that is, Sarpagine-type, koumine-type, humantenine-type, gelsedine-type, and gelsemine-type, based on their structure.
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Recent advances in the chemistry of Gelsemium alkaloids
Structure and chemistry (Part C), 1995Co-Authors: Hiromitsu Takayama, Shin-ichiro SakaiAbstract:Publisher Summary This chapter reviews the recent intensive research that led to significant progress in the field of Gelsemium alkaloid chemistry. It presents alkaloids isolated from the Gelsemium species. The structure elucidation of the representative alkaloids using mainly spectroscopic methods is described. The chapter discusses the biogenetic speculation of the structurally unique Gelsemium alkaloids and the biomimetic transformation of the known indole alkaloids leading to the various skeletal types of Gelsemium alkaloids. A genuine indole nucleus is present only in the Sarpagine group and sempervirine among the many skeletal classes of the Gelsemium alkaloids. The Sarpagine group found in the Gelsemium species consists of six indole alkaloids, 19( Z )-akuammidine (koumicine), koumicine N -oxide, koumidine, 16 -epi- voacarpine, 19(Z)-anhydrovobasine-diol, and N a -methoxy-19( Z )-anhydrovobasinediol. The structure elucidation of the indole alkaloid, the so-called akuammidine isolated from Gelsemium elegans is discussed in the chapter. The configuration of the ethylidene side chain was considered the 19( E ) form as generally found in the monoterpenoid indole alkaloids. The so-called akuammidine from G. elegans showed the same mass spectral fragment pattern as authentic akuammidine obtained from other plant sources.
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Synthesis of a novel gelsedine-type gelsemium alkaloid, gelsemicine
Journal of the Chemical Society Perkin Transactions 1, 1994Co-Authors: Mariko Kitajima, Hiromitsu Takayama, Shin-ichiro SakaiAbstract:A Gelsemium alkaloid, gelsemicine is synthesized from a Sarpagine-type indole alkaloid, gardnerine, via humantenine, gelselegine- and gelsenicine-type compounds.
Tanja Gaich - One of the best experts on this subject based on the ideXlab platform.
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Structure‐Pattern‐Based Total Synthesis
Chemistry (Weinheim an der Bergstrasse Germany), 2019Co-Authors: Christa K. G. Gerlinger, Tanja GaichAbstract:In this article the concept of structure-pattern-recognition and its application to total synthesis is summarized. By applying this synthetic strategy to the two biogenetically unrelated natural product families Sarpagine and Stemona alkaloids, a drastic increase of synthetic efficiency could be achieved. To highlight its potential, this strategy is compared with some elegant target-oriented syntheses. The importance of strategic planning and synthesis design is clearly demonstrated.
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gram scale total synthesis of Sarpagine alkaloids and non natural derivatives
Chemistry: A European Journal, 2019Co-Authors: Heiko Rebmann, Christa K. G. Gerlinger, Tanja GaichAbstract:This work describes the total synthesis of three members of the Sarpagine alkaloid family and ten non-natural congeners through an improved synthetic sequence, which was designed for gram-scale production of materials suited for structure-activity relationship (SAR) studies. Furthermore, the manuscript details how the synthetic route was used to access the biogenetically completely unrelated Stemona alkaloid parvineostemonine (34), providing a showcase for efficient synthetic design.
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Gram‐Scale Total Synthesis of Sarpagine Alkaloids and Non‐Natural Derivatives
Chemistry (Weinheim an der Bergstrasse Germany), 2019Co-Authors: Heiko Rebmann, Christa K. G. Gerlinger, Tanja GaichAbstract:This work describes the total synthesis of three members of the Sarpagine alkaloid family and ten non-natural congeners through an improved synthetic sequence, which was designed for gram-scale production of materials suited for structure-activity relationship (SAR) studies. Furthermore, the manuscript details how the synthetic route was used to access the biogenetically completely unrelated Stemona alkaloid parvineostemonine (34), providing a showcase for efficient synthetic design.
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Total Synthesis of Parvineostemonine by Structure Pattern Recognition: A Unified Approach to Stemona and Sarpagine Alkaloids.
Chemistry (Weinheim an der Bergstrasse Germany), 2018Co-Authors: Christa K. G. Gerlinger, Sebastian Krüger, Tanja GaichAbstract:Through structure pattern recognition based total synthesis we designed a synthesis in which two biogenetically unrelated natural product families (Stemona- and Sarpagine alkaloids) share 50 % of their synthetic sequence. In this report, the efficiency of such a strategic approach is demonstrated in the total synthesis of the Stemona alkaloid parvineostemonine, proceeding through a privileged intermediate that we have previously transformed into biogenetically completely unrelated Sarpagine alkaloids. In addition, we capitalized on the symmetry properties of the privileged intermediate, which was obtained as two regioisomers. After their separation by column chromatography the two regioisomers were converted to the corresponding pair of enantiomers by one transformation. To the best of our knowledge, this feature (conversion of regioisomers to enantiomers) has never been applied to natural product synthesis, and proved to be very valuable, since it allowed to obtain both optical antipodes of parvineostemonine in a single synthetic campaign. This not only enabled the determination of the previously undisclosed absolute configuration of the natural product, but gave 60-200 mg amounts of both enantiomers of the natural product.
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Total Syntheses of Vellosimine,N-Methylvellosimine, and 10-Methoxyvellosimine and Formal Synthesis of 16-Epinormacusine B through a [5+2] Cycloaddition
European Journal of Organic Chemistry, 2016Co-Authors: Sebastian Krüger, Tanja GaichAbstract:To date, more than 100 members of the Sarpagine alkaloid family have been isolated. Their structural variations originate from oxidative transformations of the carboskeleton and the presence of both absolute configurations at the C-16 atom, which is established in the course of their biosynthesis. More than 40 Sarpagine alkaloids belong to the either the 16-regular or 16-epi subgroups, depending on the stereochemistry at C-16. Herein, we report the formal synthesis of 16-epinormacusine B, a member of the 16-epi group, by using our well-established generalized strategy for the total synthesis of these alkaloids. Furthermore, we provide the synthetic details and pitfalls of the asymmetric total syntheses of vellosimine, N-methylvellosimine, and 10-methoxyvellosimine, all members of the 16-regular group.
Xuebin Liao - One of the best experts on this subject based on the ideXlab platform.
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Stereospecific Approach to the Synthesis of Ring-A Oxygenated Sarpagine Indole Alkaloids. Total Synthesis of the Dimeric Indole Alkaloid P-(+)-Dispegatrine and Six Other Monomeric Indole Alkaloids
The Journal of organic chemistry, 2013Co-Authors: Chitra R Edwankar, Ojas A. Namjoshi, Rahul V Edwankar, Xuebin Liao, James M CookAbstract:The first regio- and stereocontrolled total synthesis of the bisphenolic, bisquaternary alkaloid (+)-dispegatrine (1) has been accomplished in an overall yield of 8.3% (12 reaction vessels) from 5-methoxy-d-tryptophan ethyl ester (17). A crucial late-stage thallium(III) mediated intermolecular oxidative dehydrodimerization was employed in the formation of the C9–C9′ biaryl axis in 1. The complete stereocontrol observed in this key biaryl coupling step is due to the asymmetric induction by the natural Sarpagine configuration of the monomer lochnerine (6) and was confirmed by both the Suzuki and the oxidative dehydrodimerization model studies on the tetrahydro β-carboline (35). The axial chirality of the lochnerine dimer (40) and in turn dispegatrine (1) was established by X-ray crystallography and was determined to be P(S). Additionally, the first total synthesis of the monomeric indole alkaloids (+)-spegatrine (2), (+)-10-methoxyvellosimine (5), (+)-lochnerine (6), lochvinerine (7), (+)-Sarpagine (8), and...
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The Enantiospecific, Stereospecific Total Synthesis of the Ring-A Oxygenated Sarpagine Indole Alkaloids (+)-Majvinine, (+)-10-Methoxyaffinisine, and (+)-Na-MethylSarpagine, as Well as the Total Synthesis of the Alstonia Bisindole Alkaloid Macralstoni
The Journal of organic chemistry, 2003Co-Authors: Shuo Zhao, Xuebin Liao, Tao Wang, Judith L. Flippen-anderson, James M CookAbstract:The first stereospecific, enantiospecific total synthesis of the ring-A oxygenated Sarpagine indole alkaloids (+)-Na-methylSarpagine (8), (+)-majvinine (14), and (+)-10-methoxyaffinisine (49), as well as the first total synthesis of the Alstonia bisindole alkaloid macralstonidine (9), has been accomplished. This approach employed the Schollkopf chiral auxiliary for the stereospecific construction of the desired d-(+)-tryptophan unit required for the asymmetric Pictet−Spengler reaction. In addition, the strategy was doubly convergent for the enolate-mediated Pd0 coupling process and the asymmetric Pictet−Spengler reaction can be employed to synthesize both macroline (2) and Na-methylSarpagine (8), the coupling of which provides macralstonidine (9). This approach to ring-A substituted alkoxyindole alkaloids should find wide application for the synthesis of other alkaloids for it is stereospecific and either enantiomer can be prepared with ease.
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the enantiospecific stereospecific total synthesis of the ring a oxygenated Sarpagine indole alkaloids majvinine 10 methoxyaffinisine and na methylSarpagine as well as the total synthesis of the alstonia bisindole alkaloid macralstonidine
Journal of Organic Chemistry, 2003Co-Authors: Shuo Zhao, Xuebin Liao, Tao Wang, Judith L Flippenanderson, James M CookAbstract:The first stereospecific, enantiospecific total synthesis of the ring-A oxygenated Sarpagine indole alkaloids (+)-Na-methylSarpagine (8), (+)-majvinine (14), and (+)-10-methoxyaffinisine (49), as well as the first total synthesis of the Alstonia bisindole alkaloid macralstonidine (9), has been accomplished. This approach employed the Schollkopf chiral auxiliary for the stereospecific construction of the desired d-(+)-tryptophan unit required for the asymmetric Pictet−Spengler reaction. In addition, the strategy was doubly convergent for the enolate-mediated Pd0 coupling process and the asymmetric Pictet−Spengler reaction can be employed to synthesize both macroline (2) and Na-methylSarpagine (8), the coupling of which provides macralstonidine (9). This approach to ring-A substituted alkoxyindole alkaloids should find wide application for the synthesis of other alkaloids for it is stereospecific and either enantiomer can be prepared with ease.
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Stereospecific, Enantiospecific Total Synthesis of the Sarpagine Indole Alkaloids (E)16-Epiaffinisine, (E)16-Epinormacusine B, and Dehydro-16-epiaffinisine
Organic letters, 2002Co-Authors: Xuebin Liao, James M CookAbstract: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.