56245-51-3Relevant academic research and scientific papers
Five-Step Total Synthesis of (±)-Aspidospermidine by a Lactam Strategy via an Azomethine Ylide
Katahara, Seiya,Sugiyama, Yasukazu,Yamane, Mina,Komiya, Yukinori,Sato, Takaaki,Chida, Noritaka
, p. 3058 - 3063 (2021/05/04)
A five-step total synthesis of (±)-aspidospermidine (1) based on a lactam strategy is reported. Our synthesis features an iridium-catalyzed reductive Michael addition/[3+2] cycloaddition cascade to give a tricyclic ketone intermediate from a simple lactam via an azomethine ylide. The developed strategy enables easily available lactams to be used as stable surrogates of multisubstituted amines and would be applicable to a unified total synthesis of complex Aspidosperma alkaloids.
TiCl3-Mediated Synthesis of 2,3,3-Trisubstituted Indolenines: Total Synthesis of (+)-1,2-Dehydroaspidospermidine, (+)-Condyfoline, and (?)-Tubifoline
Delayre, Bastien,Piemontesi, Cyril,Wang, Qian,Zhu, Jieping
supporting information, p. 13990 - 13997 (2020/06/10)
2,3,3-Trisubstituted indolenine constitutes an integral part of many biologically important monoterpene indole alkaloids. We report herein an unprecedented access to this skeleton by a TiCl3-mediated reductive cyclization of tetrasubstituted alkenes bearing a 2-nitrophenyl substituent. The proof of concept is demonstrated firstly by accomplishing a concise total synthesis of (+)-1,2-dehydroaspidospermidine featuring a late-stage application of this key transformation. A sequence of reduction of nitroarene to nitrosoarene followed by 6π-electron-5-atom electrocyclization and a 1,2-alkyl shift of the resulting nitrone intermediate was proposed to account for the reaction outcome. A subsequent total synthesis of (+)-condyfoline not only illustrates the generality of the reaction, but also provides a mechanistic insight into the nature of the 1,2-alkyl shift. The exclusive formation of (+)-condyfoline indicates that the 1,2-alkyl migration follows a concerted Wagner–Meerwein pathway, rather than a stepwise retro-Mannich/Mannich reaction sequence. Conditions for almost quantitative conversion of (+)-condyfoline to (?)-tubifoline by way of a retro-Mannich/1,3-prototropy/transannular cyclization cascade are also documented.
Asymmetric Total Synthesis of (+)-Winchinine B
Liu, Zaimin,Ju, Xiaolin,Ma, Shiqiang,Du, Chenglong,Zhang, Weiwei,Li, Huilin,Wang, Xiaolei,Xie, Xingang,She, Xuegong
, p. 14994 - 15000 (2019/11/19)
The first asymmetric total synthesis of aspidosperma alkaloid (+)-winchinine B was achieved in 12 steps from commercially available materials. A new synthetic strategy which features an efficient aza-Michael addition, a ruthenium-catalyzed transfer dehydrogenation, and an intramolecular palladium-catalyzed oxidative coupling was adopted to install the ABC tricycle system. A one-pot process involving carbonyl reduction/iminium formation/intramolecular conjugate addition developed by our group was utilized to construct the D ring moiety.
A unified synthesis of topologically diverse: Aspidosperma alkaloids through divergent iminium-trapping
Mijangos, Marco V.,Miranda, Luis D.
, p. 9409 - 9419 (2019/01/03)
Aspidospermidine, vincadifformine, 1,2-dehydroaspidospermidine, goniomitine, and quebrachamine, five Aspidosperma alkaloids distributed within three structurally diverse topologies, were synthesized from a single molecular scaffold, namely indole-valerolactam 6. This common intermediate can be divergently manipulated, through the incorporation of conformational and electronic constraints that influence the chemo-selectivity of the iminium ion derived therefrom, between three different reaction paths: N(1) vs. C(3) cyclization (indole numbering) vs. over-reduction. Moreover, a catalytic carbene insertion for direct C(3)-H indole functionalization is reported for the first time in an approach to goniomitine (4), and a following tandem ester reduction/iminium generation/cyclization secured its tetracyclic system. The development of a highly diastereoselective one-pot hemi-reduction/cyclization/deprotection process to obtain a cis-pyridocarbazole directly allowed the synthesis of pentacyclic Aspidosperma alkaloids 1, 2, and 3.
Enantioselective Synthesis of (-)-Vallesine: Late-Stage C17-Oxidation via Complex Indole Boronation
Antropow, Alyssa H.,Garcia, Nicholas R.,White, Kolby L.,Movassaghi, Mohammad
supporting information, p. 3647 - 3650 (2018/06/26)
The first enantioselective total synthesis of (-)-vallesine via a strategy that features a late-stage regioselective C17-oxidation followed by a highly stereoselective transannular cyclization is reported. The versatility of this approach is highlighted by the divergent synthesis of the archetypal alkaloid of this family, (+)-aspidospermidine, and an A-ring-oxygenated derivative, (+)-deacetylaspidospermine, the precursor to (-)-vallesine, from a common intermediate.
Divergent Asymmetric Total Synthesis of (+)-Vincadifformine, (-)-Quebrachamine, (+)-Aspidospermidine, (-)-Aspidospermine, (-)-Pyrifolidine, and Related Natural Products
Wang, Nengzhong,Du, Shuo,Li, Dong,Jiang, Xuefeng
, p. 3167 - 3170 (2017/06/23)
A uniformly strategic total synthesis of Aspidosperma alkaloids (+)-vincadifformine, (-)-quebrachamine, (+)-aspidospermidine, (-)-aspidospermine, (-)-pyrifolidine, and nine others from efficiently constructed tricyclic ketone 13 is reported. Highlights of these divergent and practical syntheses include (i) stereoselective intermolecular [4 + 2] cycloaddition to establish a C-E ring with one all-carbon quaternary stereocenter (C-5) and two bridged contiguous cis-stereocenters (C-12 and C-19), (ii) a Pd/C-catalyzed hydrogenation/deprotection/amidation cascade process to assemble the D ring, and (iii) Fischer indolization to forge the A-B ring.
Chiral tricyclic keto-amine compound as well as synthetic method and application thereof
-
, (2017/08/29)
The invention discloses a chiral tricyclic keto-amine compound as well as a synthetic method and an application thereof. The invention discloses a (31S,6aR,9aR)-6a-ethyldecahydro-1H-pyrrolo-[3,2,1-ij]quinoline-9(2H)-ketone compound shown by a formula (1) and a preparation method thereof. According to the preparation method, the chiral tricyclic keto-amine compound is obtained through reactions of 5 steps of performing [4+2] cycloaddition on 3-ethyl-5-bromo-2-pyrone and (S)-2,3-dihydro-1H-pyrrole-1,2-di-tert-butyl dicarboxylate, performing decarboxylation, performing Pd/C catalytic hydrogenation and cyclization, and the like. The compound shown by the formula (1) is an advanced intermediate which can be used for preparing quebracho alkaloid, and the compound can be used for preparing the quebracho alkaloid and derivatives. The method starts from low-price and easily-available raw materials, and provides a good technical support for subsequent implementation of large-scale production and structure-activity relationship research of a quebracho alkaloid natural product.
Total Synthesis of (-)-Rhazinilam and Formal Synthesis of (+)-Eburenine and (+)-Aspidospermidine: Asymmetric Cu-Catalyzed Propargylic Substitution
Shemet, Andrej,Carreira, Erick M.
, p. 5529 - 5532 (2017/10/25)
A total synthesis of (-)-rhazinilam and formal syntheses of (+)-eburenine and (+)-aspidospermidine that rely on a copper(I)-catalyzed asymmetric propargylic substitution as the key step are reported. A salient feature of the reaction is the asymmetric con
Unified strategy to monoterpene indole alkaloids: Total syntheses of (±)-Goniomitine, (±)-1,2-Dehydroaspidospermidine, (±)-Aspidospermidine, (±)-Vincadifformine, and (±)-Kopsihainanine A
Wagnires, Olivier,Xu, Zhengren,Wang, Qian,Zhu, Jieping
supporting information, p. 15102 - 15108 (2014/12/11)
Total syntheses of (±)-goniomitine, (±)-1,2-dehydroaspidospermidine, (±)-aspidospermidine, (±)-vincadifformine, and (±)-kopsihainanine A were achieved featuring two common key steps: (1) a palladium-catalyzed decarboxylative vinylation that provides quick access to cyclopentene intermediates containing all of the carbons present in the natural products and (2) an integrated oxidation/reduction/cyclization (iORC) sequence for skeletal reorganization that converts the cyclopentenes to the pentacyclic structures of the natural products. By incorporation of a geometric constraint to iORC substrates, both the chemoselectivity (C7 vs N1 cyclization) and the stereoselectivity (trans- vs cis-fused ring system) of the cyclization process can be controlled.
Pd(II)-catalyzed regioselective 2-alkylation of indoles via a norbornene-mediated C-H activation: Mechanism and applications
Jiao, Lei,Herdtweck, Eberhardt,Bach, Thorsten
supporting information, p. 14563 - 14572 (2012/10/29)
A palladium-catalyzed direct 2-alkylation reaction of free N-H indoles was developed based on a norbornene-mediated regioselective cascade C-H activation. The detailed reaction mechanism was investigated by NMR spectroscopic analyses, characterization of the key intermediate, deuterium labeling experiments, and kinetic studies. The results indicate that a catalytic cycle operates, in which an N-norbornene type palladacycle is formed as the key intermediate. Oxidative addition of alkyl bromide to the Pd(II) center in this intermediate is the rate-determining step of the reaction. The synthetic utility of this indole 2-alkylation method was demonstrated by its application in natural product total synthesis. A new and general strategy to synthesize Aspidosperma alkaloids was established employing the indole 2-alkylation reaction as the key step, and two structurally different Aspidosperma alkaloids, aspidospermidine and goniomitine, were synthesized in concise routes.
