2912-09-6Relevant articles and documents
Total Synthesis of (+)-Aspidospermidine
Xu, Hongjin,Huang, He,Zhao, Cui,Song, Chuanjun,Chang, Junbiao
, p. 6457 - 6460 (2019)
A facile asymmetric total synthesis of (+)-aspidospermidine has been developed, which is accomplished in 11 steps in an overall yield of 9.6%. Key steps involve a palladium-catalyzed enantioselective decarboxylative allylation to install the quaternary ca
Enantioselective Synthesis of (-)-Vallesine: Late-Stage C17-Oxidation via Complex Indole Boronation
Antropow, Alyssa H.,Garcia, Nicholas R.,White, Kolby L.,Movassaghi, Mohammad
, 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.
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
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.
Collective synthesis of natural products by means of organocascade catalysis
Jones, Spencer B.,Simmons, Bryon,Mastracchio, Anthony,MacMillan, David W. C.
, p. 183 - 188 (2012/05/20)
Organic chemists are now able to synthesize small quantities of almost any known natural product, given sufficient time, resources and effort. However, translation of the academic successes in total synthesis to the large-scale construction of complex natural products and the development of large collections of biologically relevant molecules present significant challenges to synthetic chemists. Here we show that the application of two nature-inspired techniques, namely organocascade catalysis and collective natural product synthesis, can facilitate the preparation of useful quantities of a range of structurally diverse natural products from a common molecular scaffold. The power of this concept has been demonstrated through the expedient, asymmetric total syntheses of six well-known alkaloid natural products: strychnine, aspidospermidine, vincadifformine, akuammicine, kopsanone and kopsinine.
Flexible access to monoterpenoid indole alkaloids using a cyclopentanoid chiral building block
Hayashi, Masato,Motosawa, Keiichi,Satoh, Atsushi,Shibuya, Masatoshi,Ogasawara, Kunio,Iwabuchi, Yoshiharu
scheme or table, p. 855 - 863 (2010/10/03)
Expedient, diasterocontrolled transformations of 1 to the key synthetic intermediate of corynanthe, iboga, and aspidosperma-class of monoterpenoid indole alkaloids which led up to a formal synthesis of (+)-20R- dihydrocleavamine, (-)-eburnamonine, and a total synthesis of (+)-aspidospermidine (2) have been demonstrated.
Domino double Michael-Claisen cyclizations: A powerful general tool for introducing quaternary stereocenters at C(4) of cyclohexane-1,3-diones and total synthesis of diverse families of sterically congested alkaloids
Ishikawa, Teruhiko,Kudo, Kazuhiro,Kuroyabu, Ken,Uchida, Satoshi,Kudoh, Takayuki,Saito, Seiki
, p. 7498 - 7508 (2008/12/22)
(Chemical Equation Presented) Reactions of substituted acetone derivatives with acrylic acid esters (>200 mol %) in the presence of t-BuOK (200 mol %) in t-BuOH-THF (1:1 by volume) turned out to proceed as a cascade process consisting of the first Michael addition, the second Michael addition, and the last Claisen reaction to afford 4,4-disubstituted cyclohexane-1,3-diones. Only more substituted enolates play the role of a Michael donor in this cascade process, and therefore the ketone took up two alkoxycarbonylethyl groups on the same carbon bearing more substituents. Such intermediates were followed by intramolecular Claisen reactions leading to cyclohexane-1,3-diones bearing quaternary stereogenic centers at C(4), which bears an alkoxycarbonylethyl group and the substituent of the starting acetone derivatives. Thus-obtained 4,4-disubstituted cyclohexane-1,3-diones were successfully employed for total syntheses of intricate alkaloids of biological interest such as (+)-aspidospermidine, (±)-galanthamine, (±)-lycoramine, and (±)-mesembrine, all featuring quaternary stereogenic centers. DFT calculations provided us with clear-cut explanations for the observed chemoselectivity of the cascade process involving ketone-based enolates under thermodynamically controlled conditions.
Revisiting a classic approach to the Aspidosperma alkaloids: An intramolecular Schmidt reaction mediated synthesis of (+)-aspidospermidine
Iyengar, Rajesh,Schildknegt, Klaas,Morton, Martha,Aube, Jeffrey
, p. 10645 - 10652 (2007/10/03)
A total synthesis of (+)-aspidospermidine (1) is described. The key reactions used in the synthesis of this pentacyclic Aspidosperma alkaloid were a deracemizing imine alkylation/Robinson annulation sequence, a selective "redox ketalization", and an intramolecular Schmidt reaction. A Fischer indolization step carried out on a tricyclic ketone mirrored the sequence reported by Stork and Dolfini in their classic aspidospermine synthesis.
An efficient approach to Aspidosperma alkaloids via [4 + 2] cycloadditions of aminosiloxydienes: Stereocontrolled total synthesis of (±)-tabersonine. Gram-scale catalytic asymmetric syntheses of (+)-tabersonine and (+)-16-methoxytabersonine. Asymmetric syntheses of (+)-aspidospermidine and (-)-quebrachamine
Kozmin, Sergey A.,Iwama, Tetsuo,Huang, Yong,Rawal, Viresh H.
, p. 4628 - 4641 (2007/10/03)
Described is a concise, highly stereocontrolled strategy to the Aspidosperma family of indole alkaloids, one that is readily adapted to the asymmetric synthesis of these compounds. The strategy is demonstrated by the total synthesis of (±)-tabersonine (rac-1), proceeding through a 12-step sequence. The basis for this approach was provided by a highly regio- and stereoselective [4 + 2] cycloaddition of 2-ethylacrolein with 1-amino-3-siloxydiene developed in our laboratory. Subsequent elaboration of the initial adduct into the hexahydroquinoline DE ring system was accomplished efficiently by a ring-closing olefin metathesis reaction. A novel ortho nitrophenylation of an enol silyl ether with (o-nitrophenyl)phenyliodonium fluoride was developed to achieve an efficient, regioselective introduction of the requisite indole moiety. The final high-yielding conversion of the ABDE tetracycle into pentacyclic target rac-1 relied on intramolecular indole alkylation and regioselective C-carbomethoxylation. Our approach differs strategically from previous routes and contains built-in flexibility necessary to access many other members of the Aspidosperma family of indole alkaloids. The versatility of the synthetic strategy was illustrated through the asymmetric syntheses of the following Aspidosperma alkaloids: (+)-aspidospermidine, (-)-quebrachamine, (-)-dehydroquebrachamine, (+)-tabersonine, and (+)-16-methoxytabersonine. Of these, (+)-tabersonine and (+)-16-methoxytabersonine were synthesized in greater than 1 -g quantities and in enantiomerically enriched form (～95% ee). The pivotal asymmetry- introducing step was a catalyzed enantioselective Diels-Alder reaction, which proceeded to afford the cycloadducts in up to 95% ee. Significantly, the synthetic sequence was easy to execute and required only four purifications over the 12-step synthetic route.
Total synthesis of (+)-aspidospermidine: A new strategy for the enantiospecific synthesis of aspidosperma alkaloids
Marino, Joseph P.,Rubio, Maria B.,Cao, Ganfeng,De Dios, Alfonso
, p. 13398 - 13399 (2007/10/03)
A new strategy was developed for the enantiospecific synthesis of aspidosperma alkaloids. The key steps involve a novel ketene-lactonization reaction of a chiral vinyl sulfoxide to efficiently set up the quaternary carbon center, and a tandem Michael addi
